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Sample records for c-induced genotoxic damage

  1. Effect of recombinant human erythropoietin on mitomycin C-induced oxidative stress and genotoxicity in rat kidney and heart tissues.

    Science.gov (United States)

    Rjiba-Touati, K; Ayed-Boussema, I; Guedri, Y; Achour, A; Bacha, H; Abid-Essefi, S

    2016-01-01

    Mitomycin C (MMC) is an antineoplastic agent used for the treatment of several human malignancies. Nevertheless, the prolonged use of the drug may result in a serious heart and kidney injuries. Recombinant human erythropoietin (rhEPO) has recently been shown to exert an important cytoprotective effect in experimental brain injury and ischemic acute renal failure. The aim of the present work is to investigate the cardioprotective and renoprotective effects of rhEPO against MMC-induced oxidative damage and genotoxicity. Our results showed that MMC induced oxidative stress and DNA damage. rhEPO administration in any treatment conditions decreased oxidative damage induced by MMC. It reduced malondialdehyde and protein carbonyl levels. rhEPO ameliorated reduced glutathione plus oxidized glutathione modulation and the increased catalase activity after MMC treatment. Furthermore, rhEPO restored DNA damage caused by MMC. We concluded that rhEPO administration especially in pretreatment condition protected rats against MMC-induced heart and renal oxidative stress and genotoxicity. PMID:25733728

  2. Genotoxicity of refinery waste assessed by some DNA damage tests.

    Science.gov (United States)

    Gupta, Amit Kumar; Ahmad, Irshad; Ahmad, Masood

    2015-04-01

    Refinery waste effluent is well known to contain polycyclic aromatic hydrocarbons, phenols and heavy metals as potentially genotoxic substances. The aim of the present study was to assess the genotoxic potential of Mathura refinery wastewater (MRWW) by various in vitro tests including the single cell gel electrophoresis, plasmid nicking assay and S1 nuclease assay. Treatment of human lymphocytes to different MRWW concentrations (0.15×, 0.3×, 0.5× and 0.78×) caused the formation of comets of which the mean tail lengths increased proportionately and differed significantly from those of unexposed controls. The toxic effect of MRWW on DNA was also studied by plasmid nicking assay and S1 nuclease assay. Strand breaks formation in the MRWW treated pBR322 plasmid confirmed its genotoxic effect. Moreover, a dose dependent increase in cleavage of calf thymus DNA in S1 nuclease assay was also suggestive of the DNA damaging potential of MRWW. A higher level of ROS generation in the test water sample was recorded which might be contributing to its genotoxicity. Interaction between the constituents of MRWW and calf thymus DNA was also ascertained by UV-visible spectroscopy.

  3. Genotoxicity of formaldehyde: Molecular basis of DNA damage and mutation

    Directory of Open Access Journals (Sweden)

    Masanobu eKawanishi

    2014-09-01

    Full Text Available Formaldehyde is commonly used in the chemical industry and is present in the environment, such as vehicle emissions, some building materials, food and tobacco smoke. It also occurs as a natural product in most organisms, the sources of which include a number of metabolic processes. It causes various acute and chronic adverse effects in humans if they inhale its fumes. Among the chronic effects on human health, we summarize data on genotoxicity and carcinogenicity in this review, and we particularly focus on the molecular mechanisms involved in the formaldehyde mutagenesis. Formaldehyde mainly induces N-hydroxymethyl mono-adducts on guanine, adenine and cytosine, and N-methylene crosslinks between adjacent purines in DNA. These crosslinks are types of DNA damage potentially fatal for cell survival if they are not removed by the nucleotide excision repair pathway. In the previous studies, we showed evidence that formaldehyde causes intra-strand crosslinks between purines in DNA using a unique method (Matsuda et al. Nucleic Acids Res. 26, 1769-1774,1998. Using shuttle vector plasmids, we also showed that formaldehyde as well as acetaldehyde induces tandem base substitutions, mainly at 5’-GG and 5’-GA sequences, which would arise from the intra-strand crosslinks. These mutation features are different from those of other aldehydes such as crotonaldehyde, acrolein, glyoxal and methylglyoxal. These findings provide molecular clues to improve our understanding of the genotoxicity and carcinogenicity of formaldehyde.

  4. DNA damage in caged Gammarus fossarum amphipods: A tool for freshwater genotoxicity assessment

    Energy Technology Data Exchange (ETDEWEB)

    Lacaze, Emilie [Universite de Lyon, INRA-ENTPE, Laboratoire des Sciences de l' Environnement, rue Maurice Audin, Vaulx en Velin F-69518 (France); Cemagref, Unite de Recherche des Milieux Aquatiques, (UR MALY), 3 bis quai Chauveau, 69336 Lyon, Cedex 9 (France); Devaux, Alain [Universite de Lyon, INRA-ENTPE, Laboratoire des Sciences de l' Environnement, rue Maurice Audin, Vaulx en Velin F-69518 (France); Mons, Raphael [Cemagref, Unite de Recherche des Milieux Aquatiques, (UR MALY), 3 bis quai Chauveau, 69336 Lyon, Cedex 9 (France); Bony, Sylvie [Universite de Lyon, INRA-ENTPE, Laboratoire des Sciences de l' Environnement, rue Maurice Audin, Vaulx en Velin F-69518 (France); Garric, Jeanne [Cemagref, Unite de Recherche des Milieux Aquatiques, (UR MALY), 3 bis quai Chauveau, 69336 Lyon, Cedex 9 (France); Geffard, Alain [EA 2069 URVVC-SE, Laboratoire d' Eco-Toxicologie, UFR Sciences, Moulin de la Housse, BP 1039, 51687 Reims Cedex 2 (France); Geffard, Olivier, E-mail: olivier.geffard@cemagref.fr [Cemagref, Unite de Recherche des Milieux Aquatiques, (UR MALY), 3 bis quai Chauveau, 69336 Lyon, Cedex 9 (France)

    2011-06-15

    The aim of this study was to propose a tool for freshwater environmental genotoxicity assessment using Gammarus fossarum, a high ecologically relevant species. In a first part, gammarids were caged upstream and downstream wastewater treatment plant effluent output. The sensitivity of genotoxic responses of haemocytes, oocytes and spermatozoa was compared using the Comet assay. Spermatozoa appeared to be the most sensitive, suitable and relevant cell type for genotoxicity risk assessment. In a second part, a watershed-scale study was conducted over 2 years to evaluate the applicability of our caging procedure. The genotoxic impact of a contamination was followed, taking into account seasonal variability. DNA damage in spermatozoa exhibited low basal level and low variability in control upstream sites, providing a reliable discrimination of polluted sites. Finally, DNA damage in caged G. fossarum has been proved to be a sensitive and reproducible tool for freshwater genotoxicity assessment. - Highlights: > Two different contamination contexts: WWTP effluents and polymetallic contamination. > DNA damage in caged Gammarus fossarum is a sensitive tool for freshwater quality assessment. > Spermatozoa is the most relevant cell type for biomonitoring freshwater genotoxicity. > Combining biomarker responses with analytical chemistry provides rich ecotoxicological information. - We propose an approach to assess freshwater genotoxicity in the field based on caged Gammarus fossarum (Crustacea, amphipoda).

  5. The role of intracellular redox imbalance in nanomaterial induced cellular damage and genotoxicity

    DEFF Research Database (Denmark)

    Kermanizadeh, Ali; Chauché, Caroline; Brown, David M;

    2015-01-01

    as one of the main contributors to nanomaterial (NM) induced adverse effects. One of the most important and widely investigated of these effects is genotoxicity. In general, systems that defend an organism against oxidative damage to DNA are very complex and include prevention of reactive oxygen species...

  6. Genotoxic damage in pathology anatomy laboratory workers exposed to formaldehyde

    International Nuclear Information System (INIS)

    Formaldehyde (FA) is a chemical traditionally used in pathology and anatomy laboratories as a tissue preservative. Several epidemiological studies of occupational exposure to FA have indicated an increased risk of nasopharyngeal cancers in industrial workers, embalmers and pathology anatomists. There is also a clear evidence of nasal squamous cell carcinomas from inhalation studies in the rat. The postulated mode of action for nasal tumours in rats was considered biologically plausible and considered likely to be relevant to humans. Based on the available data IARC, the International Agency for Research on Cancer, has recently classified FA as a human carcinogen. Although the in vitro genotoxic as well as the in vivo carcinogenic potentials of FA are well documented in mammalian cells and in rodents, evidence for genotoxic effects and carcinogenic properties in humans is insufficient and conflicting thus remains to be more documented. To evaluate the genetic effects of long-term occupational exposure to FA a group of 30 Pathological Anatomy laboratory workers was tested for a variety of biological endpoints, cytogenetic tests (micronuclei, MN; sister chromatid exchange, SCE) and comet assay. The level of exposure to FA was evaluated near the breathing zone of workers, time weighted average of exposure was calculated for each subject. The association between the biomarkers and polymorphic genes of xenobiotic metabolising and DNA repair enzymes was also assessed. The mean level of exposure was 0.44 ± 0.08 ppm (0.04-1.58 ppm). MN frequency was significantly higher (p = 0.003) in the exposed subjects (5.47 ± 0.76) when compared with controls (3.27 ± 0.69). SCE mean value was significantly higher (p < 0.05) among the exposed group (6.13 ± 0.29) compared with control group (4.49 ± 0.16). Comet assay data showed a significant increase (p < 0.05) of TL in FA-exposed workers (60.00 ± 2.31) with respect to the control group (41.85 ± 1.97). A positive correlation was

  7. Association of HSP70 and genotoxic damage in lymphocytes of workers exposed to coke-oven emission

    OpenAIRE

    Xiao, Chengfeng; Chen, Sheng; Li, Jizhao; Hai, Tao; Lu, Qiaofa; Sun, Enling; Wang, Ruibo; Tanguay, Robert M.; Wu, Tangchun

    2002-01-01

    Heat shock proteins (Hsps) have been reported to protect cells, tissues, and organisms against damage from a wide variety of stressful stimuli. Whether they protect against deoxyribonucleic acid (DNA) damage in individuals exposed to environmental stresses and chemical carcinogens is unknown. In the study, we investigated the association between Hsp70 levels (the most abundant mammalian Hsp) and genotoxic damage in lymphocytes of workers exposed to coke-oven emission using Western dot blot an...

  8. Importance of UVA photoprotection as shown by genotoxic related endpoints: DNA damage and p53 status

    Energy Technology Data Exchange (ETDEWEB)

    Marrot, Laurent [L' Oreal Research, Life Sciences Research, Phototoxicology Unit, Genotoxicity Group 1, av. E. Schueller, 93600 Aulnay-Sous-Bois (France)]. E-mail: lmarrot@rd.loreal.com; Belaidi, Jean-Philippe [L' Oreal Research, Life Sciences Research, Phototoxicology Unit, Genotoxicity Group 1, av. E. Schueller, 93600 Aulnay-Sous-Bois (France); Meunier, Jean-Roch [L' Oreal Research, Life Sciences Research, Phototoxicology Unit, Genotoxicity Group 1, av. E. Schueller, 93600 Aulnay-Sous-Bois (France)

    2005-04-01

    In order to demonstrate the importance of photoprotection in the UVA range (320-400 nm), an in vitro approach where sun formulations are spread on a quartz slide, and placed over human keratinocytes in culture is proposed as a convenient test for photoprotection assessment at the DNA level. Using the comet assay, DNA strand breaks, oxidative DNA damage or drug-induced DNA breaks were assessed. Accumulation of p53 protein was also studied as a marker for UV-induced genotoxic stress. Such a method was used to compare two formulations with different photostability. Spectroradiometry showed that a photounstable formulation lost its effectiveness in UVA screening when pre-irradiated by simulated sunlight (UVB + UVA). As a consequence, it was also shown that this formulation was not as protective as the photostable one at the genomic level. These data demonstrate that the loss of absorbing efficiency within UVA wavelengths due to photounstability may have detrimental consequences leading to impairments implicated in genotoxic events.

  9. Comparison of Genotoxic Damage in Monolayer Cell and Three-Dimensional Tissue-Like Cell Assemblies

    Science.gov (United States)

    Behravesh, E.; Emami, K.; Wu, H.; Gonda, S.

    Risk assessment for the biological effects of high-energy charged particles, ranging from protons to iron nuclei, encountered in space is essential for the success of long-term space exploration. While prokaryotic and eukaryotic cell models, developed in our lab and others, have advanced our understanding of many aspects of genotoxicity, there is a need for in vitro models to assess the risk to humans from space radiation insults that are representative of the cellular interactions present in tissues and capable of quantifying genotoxic damage. Toward this overall goal, the objective of this study is to examine the effect of the localized microenvironment of cells, either cultured as 2-dimensional monolayers (2D) or 3-dimensional aggregates (3D), on the rate and type of genotoxic damage, and to examine those effects after the normal cell repair processes. Rodent transgenic cell lines containing 50-70 copies of a transgene were utilized to provide the enhanced sensitivity required to enable the identification and quantification of the types of mutational events incurred from exposure to iron charged particles which makes up a significant portion of Space radiation. Although the LacI target of this system is ~1000 bps, each copy of the entire construct is over 45 kbps. The utilization of this system allows for the quantification of mutational frequency and type for the LacI target as well as assessment of DNA damage for the entire 45 kbp construct. The samples were exposed to high-LET iron charged particles at Brookhaven National Laboratory's AGS/NSRL facilities for a total dose of 0, 0.1, 0.25, 0.5, 1.0, and 2.0 Gy and recovered after 0, 1, and 7 days of tissue culture post-irradiation. The mutational frequency was found to be greater for the 3D samples when compared to the 2D samples at all doses. In addition, there was increased mutational frequency with 7 days culture post irradiation when compared to samples analyzed immediately after exposure. DNA sequencing of

  10. Electrochemiluminescent Arrays for Cytochrome P450-Activated Genotoxicity Screening. DNA Damage from Benzo[a]pyrene Metabolites

    Science.gov (United States)

    Hvastkovs, Eli G.; So, Minjeong; Krishnan, Sadagopan; Bajrami, Besnik; Tarun, Maricar; Jansson, Ingela; Schenkman, John B.; Rusling, James F.

    2007-01-01

    Arrays suitable for genotoxicity screening are reported that generate metabolites from cytochrome P450 enzymes (CYPs) in thin-film spots. Array spots containing DNA, various human cyt P450s, and electrochemiluminescence (ECL) generating metallopolymer [Ru(bpy)2PVP10]2+ were exposed to H2O2 to activate the enzymes. ECL from all spots was visualized simultaneously using a CCD camera. Using benzo[a]pyrene as a test substrate, enzyme activity for producing DNA damage in the arrays was found in the order CYP1B1 > CYP1A2 > CYP1A1 > CYP2E1 > myoglobin, the same as the order of their metabolic activity. Thus, these arrays estimate the relative propensity of different enzymes to produce genotoxic metabolites. This is the first demonstration of ECL arrays for high-throughput in vitro genotoxicity screening. PMID:17261025

  11. Procyanidins from grape seeds protect against phorbol ester-induced oxidative cellular and genotoxic damage

    Institute of Scientific and Technical Information of China (English)

    Yin LU; Wan-zhou ZHAO; Zai CHANG; Wen-xing CHEN; Lin LI

    2004-01-01

    AIM: To evaluate the inhibitory effects of Vitis vinifera procyanidins (PAs) on carcinogen-induced oxidative stress.METHODS: The single cell gel electrophoresis technique (comet assay) was employed to detect DNA damage induced by the carcinogen phorbol-12-myristate-13-acetate (PMA). The release of hydrogen peroxidase from polymorphonuclear leukocytes (PMNs) was assayed by the horseradish peroxidase-mediated oxidation of phenol red. The microplate assay was used to detect the presence of oxidative products by means of 2',7'-dichlorofiuorescindiacetate (DCFH-DA). The superoxide dismutase (SOD) activity of liver mitochondria was assayed, based on the ability of SOD to inhibit the generation of superoxidate anions by the xanthine-xanthine oxidase system. The malondialdehyde (MDA) level was determined by the thiobarbimric acid (TBA) assay. RESULTS: DNA of NIH3T3 cells was significantly damaged after addition of PMA. The length of the comet tail was observed ,while in normal cells the comet tail could not be observed. PAs showed significant protective effects on carcinogen PMA-induced DNA damage. Through assessment of DCFH-DA oxidation, PAs were shown to inhibit the PMA-induced release of hydrogen peroxide by PMNs, and to inhibit respiratory burst activity in NIH3T3 mouse fibroblasts. Ex vivo study showed that serum from rats administered with PAs displayed similar effects in a dose-dependent manner. In addition, PAs suppressed liver mitochondrial lipid peroxidation induced by PMA. PAs protected the activity of SOD and decreased the level of MDA in liver mitochondria damaged by PMA. CONCLUSION: Dietary PAs from grape seeds protect against carcinogen-induced oxidative cellular and genotoxic damage.

  12. ZnO nanoparticle tracking from uptake to genotoxic damage in human colon carcinoma cells.

    Science.gov (United States)

    Condello, Maria; De Berardis, Barbara; Ammendolia, Maria Grazia; Barone, Flavia; Condello, Giancarlo; Degan, Paolo; Meschini, Stefania

    2016-09-01

    Zinc Oxide (ZnO) nanoparticles are widely used both in the industry and in biomedical applications for their chemical and physical nanomaterial properties. It is therefore essential to go in depth into the cytotoxicity mechanisms and interactions between nanomaterials and cells. The aim of this work was to evaluate the dissolution of ZnO nanoparticles and their uptake, from a few minutes after treatments up to 24h. ZnO nanoparticles routes of entry into the human colon carcinoma cells (LoVo) were followed at different times by a thorough ultrastructural investigation and semiquantitative analysis. The intracellular release of Zn(2+) ions by Zinquin fluorescent dye, and phosphorylated histone H2AX (γ-H2AX) expression were evaluated. The genotoxic potential of ZnO nanoparticles was also investigated by determining the levels of 8-hydroxyl-2'-deoxyguanosine (8-oxodG). The experimental data show that ZnO nanoparticles entered LoVo cells by either passive diffusion or endocytosis or both, depending on the agglomeration state of the nanomaterial. ZnO nanoparticles coming into contact with acid pH of lysosomes altered organelles structure, resulting in the release of Zn(2+) ions. The simultaneous presence of ZnO nanoparticles and Zn(2+) ions in the LoVo cells determined the formation of reactive oxygen species at the mitochondrial and nuclear level, inducing severe DNA damage. PMID:27317967

  13. Follow-Up Genotoxic Study: Chromosome Damage Two and Six Years after Exposure to the Prestige Oil Spill.

    Directory of Open Access Journals (Sweden)

    Kristin Hildur

    Full Text Available The north-west coast of Spain was heavily contaminated by the Prestige oil spill, in 2002. Individuals who participated in the clean-up tasks showed increased chromosome damage two years after exposure. Long-term clinical implications of chromosome damage are still unknown.To realize a follow-up genotoxic study to detect whether the chromosome damage persisted six years after exposure to the oil.Follow-up study.Fishermen cooperatives in coastal villages.Local fishermen who were highly exposed (n = 52 and non-exposed (n = 23 to oil seven years after the spill.Chromosome damage in circulating lymphocytes.Chromosome damage in exposed individuals persists six years after oil exposure, with a similar incidence than those previously detected four years before. A surprising increase in chromosome damage in non-exposed individual was found six years after Prestige spill vs. those detected two years after the exposure.The sample size and the possibility of some kind of selection bias should be considered. Genotoxic results cannot be extrapolated to the approximately 300,000 individuals who participated occasionally in clean-up tasks.The persistence of chromosome damage detected in exposed individuals six years after oil exposure seems to indicate that the cells of the bone marrow are affected. A surprising increase in chromosome damage in non-exposed individuals detected in the follow-up study suggests an indirect exposition of these individuals to some oil compounds or to other toxic agents during the last four years. More long-term studies are needed to confirm the presence of chromosome damage in exposed and non-exposed fishermen due to the association between increased chromosomal damage and increased risk of cancer. Understanding and detecting chromosome damage is important for detecting cancer in its early stages. The present work is the first follow-up cytogenetic study carried out in lymphocytes to determine genotoxic damage evolution between two

  14. Development of a Fish Cell Biosensor System for Genotoxicity Detection Based on DNA Damage-Induced Trans-Activation of p21 Gene Expression

    Directory of Open Access Journals (Sweden)

    Huarong Guo

    2012-09-01

    Full Text Available p21CIP1/WAF1 is a p53-target gene in response to cellular DNA damage. Here we report the development of a fish cell biosensor system for high throughput genotoxicity detection of new drugs, by stably integrating two reporter plasmids of pGL3-p21-luc (human p21 promoter linked to firefly luciferase and pRL-CMV-luc (CMV promoter linked to Renilla luciferase into marine flatfish flounder gill (FG cells, referred to as p21FGLuc. Initial validation of this genotoxicity biosensor system showed that p21FGLuc cells had a wild-type p53 signaling pathway and responded positively to the challenge of both directly acting genotoxic agents (bleomycin and mitomycin C and indirectly acting genotoxic agents (cyclophosphamide with metabolic activation, but negatively to cyclophosphamide without metabolic activation and the non-genotoxic agents ethanol and D-mannitol, thus confirming a high specificity and sensitivity, fast and stable response to genotoxic agents for this easily maintained fish cell biosensor system. This system was especially useful in the genotoxicity detection of Di(2-ethylhexyl phthalate (DEHP, a rodent carcinogen, but negatively reported in most non-mammalian in vitro mutation assays, by providing a strong indication of genotoxicity for DEHP. A limitation for this biosensor system was that it might give false positive results in response to sodium butyrate and any other agents, which can trans-activate the p21 gene in a p53-independent manner.

  15. Histopathological, oxidative damage, biochemical, and genotoxicity alterations in hepatic rats exposed to deltamethrin: modulatory effects of garlic (Allium sativum).

    Science.gov (United States)

    Ncir, Marwa; Ben Salah, Ghada; Kamoun, Hassen; Makni Ayadi, Fatma; Khabir, Abdelmajid; El Feki, Abdelfattah; Saoudi, Mongi

    2016-06-01

    Deltamethrin is a pesticide widely used as a synthetic pyrethroid. The aim of this study was undertaken to investigate the effects of deltamethrin to induce oxidative stress and changes in biochemical parameters, hepatotoxicity and genotoxicity in female rats following a short-term (30 days) oral exposure and attenuation of these effects by Allium sativum extract. Indeed, Allium sativum is known to be a good antioxidant food resource which helps destroy free radical particles. Our results showed that deltamethrin treatment caused an increase in liver enzyme activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH); and hepatic lipid peroxidation (LPO) level. However, it induced a decrease in activities of hepatic catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) (p < 0.01). Allium sativum extract normalized significantly (p < 0.01) the mentioned parameters in deltamethrin-treated rats. For genotoxic evaluation, deltamethrin treatment showed a significant increase in frequencies of micronucleus in bone-marrow cells. Micronucleus formation is an indicator of chromosomal damage which has been increasingly used to detect the genotoxic potential of environmental pests. The present study showed that Allium sativum diminished the adverse effects induced by this synthetic pyrethroid insecticide. PMID:26974685

  16. Effects of chronic exposure to benzalkonium chloride in Oncorhynchus mykiss: cholinergic neurotoxicity, oxidative stress, peroxidative damage and genotoxicity.

    Science.gov (United States)

    Antunes, S C; Nunes, B; Rodrigues, S; Nunes, R; Fernandes, J; Correia, A T

    2016-07-01

    Benzalkonium chloride (BAC) is one of the most used conservatives in pharmaceutical preparations. However, its use is limited to a small set of external use formulations, due to its high toxicity. Benzalkonium chloride effects are related to the potential exertion of deleterious effects, mediated via oxidative stress and through interaction with membrane enzymes, leading to cellular damage. To address the ecotoxicity of this specific compound rainbow trouts were chronically exposed to BAC at environmental relevant concentrations (ranging from 0.100 to 1.050mg/L), and the biological response of cholinergic neurotoxicity, modulation of the antioxidant defense, phase II metabolism, lipid peroxidation and genotoxicity was studied. The obtained results showed a dual pattern of antioxidant response, with significant alterations in catalase activity (starting at 0.180mg/L), and lipid peroxidation, for intermediate (0.180 and 0.324mg/L) concentrations. No significant alterations occurred for glutathione-S-transferases activity. An unexpected increased of the acetylcholinesterase activity was also recorded for the individuals exposed to higher concentrations of BAC (starting at 0.180mg/L). Furthermore, exposure to BAC resulted in the establishment of genotoxic alterations, observable (for the specific case of the comet assay results) for all tested BAC concentrations. However, and considering that the oxidative response was not devisable, other mechanisms may be involved in the genotoxic effects reported here. PMID:27280532

  17. Electrochemiluminescent Arrays for Cytochrome P450-Activated Genotoxicity Screening. DNA Damage from Benzo[a]pyrene Metabolites

    OpenAIRE

    Hvastkovs, Eli G.; So, Minjeong; Krishnan, Sadagopan; Bajrami, Besnik; Tarun, Maricar; Jansson, Ingela; Schenkman, John B.; Rusling, James F.

    2007-01-01

    Arrays suitable for genotoxicity screening are reported that generate metabolites from cytochrome P450 enzymes (CYPs) in thin-film spots. Array spots containing DNA, various human cyt P450s, and electrochemiluminescence (ECL) generating metallopolymer [Ru(bpy)2PVP10]2+ were exposed to H2O2 to activate the enzymes. ECL from all spots was visualized simultaneously using a CCD camera. Using benzo[a]pyrene as a test substrate, enzyme activity for producing DNA damage in the arrays was found in th...

  18. Evaluation of genotoxic risk and oxidative DNA damage in mammalian cells exposed to mycotoxins, patulin and citrinin

    International Nuclear Information System (INIS)

    Mycotoxins are fungal secondary metabolites with very diversified toxic effects in humans and animals. In the present study, patulin (PAT) and citrinin (CTN), two prevalent mycotoxins, were evaluated for their genotoxic effects and oxidative damage to mammalian cells, including Chinese hamster ovary cells (CHO-K1), human peripheral blood lymphocytes, and human embryonic kidney cells (HEK293). PAT, but not CTN, caused a significant dose-dependent increase in sister chromatid exchange (SCE) frequency in both CHO-K1 and human lymphocytes. PAT also elevated the levels of DNA gap and break in treated CHO-K1. In the single cell gel electrophoresis (SCGE) assay, exposure of HEK293 to concentrations above 15 μM of PAT induced DNA strand breaks; the tail moment values also greatly increased after posttreatment with formamidopyrimidine-DNA glycosylase (Fpg). This suggests that in human cells PAT is a potent clastogen with the ability to cause oxidative damage to DNA. However, no significant change in the tail moment values in CTN-treated cultures was found, suggesting that CTN is not genotoxic to HEK293. Incubation of HEK293 with CTN increased the mRNA level of heat shock protein 70 (HSP70), but not that of human 8-hydroxyguanine DNA glycosylase 1 (hOGG1). PAT treatment did not modulate the expression of either HSP70 or hOGG1 mRNA

  19. Protective role of taurine against genotoxic damage in mice treated with methotrexate and tamoxfine.

    Science.gov (United States)

    Alam, Sally S; Hafiz, Nagla A; Abd El-Rahim, Abeer H

    2011-01-01

    The genotoxic actions of anti-neoplastic drugs can lead to the development of secondary cancers in patients in extended remission. One of the most attractive approaches to disease prevention involves the use of natural antioxidants to protect tissue against toxic injury. We investigated the modulatory effects of exogenously administered taurine, on the genotoxicity of two well known anti-neoplastic drugs methotrexate (MTX) and tamoxifen (TAM) in Swiss albino mice. The animals were randomly divided into six groups consisting of ten mice each. Two groups were received single intraperitoneal injection of MTX (10 mg/kgb.wt.) and TAM (50 mg/kgb.wt.) to induce genotoxicity. Two other groups were treated orally with taurine (100 mg/kgb.wt.) for nine days prior to MTX and TAM administration. A vehicle treated control group and taurine control groups were also included. The protective effects of taurine were monitored by apoptosis assays and level of reduced glutathione (GSH), a key antioxidant, in liver, chromosomal aberrations in somatic and germ cells as well as sperm count, motility and morphology. The results indicated that taurine pre-treatment showed significant increment in the levels of GSH content, reduction in DNA fragmentation and ladder formation in hepatic tissue, suggesting the antioxidant activity of taurine may reduce the toxic effects of MTX and TAM. Treatment with taurine showed also significant reduction in the frequency of chromosomal aberrations in both somatic and germ cells. Moreover, it increases sperm count and motility, and decreases the incidence of sperm abnormalities. In conclusion, it appears that taurine protects against anti-neoplastic drugs-induced genotoxicity in somatic and germ tissues and may be of therapeutic potential in alleviating the risk of secondary tumors in chemotherapy.

  20. Comparison of Genotoxic Damage in Monolayer Cell Cultures and Three-Dimensional Tissue-Like Cell Assemblies

    Science.gov (United States)

    Behravesh, E.; Emami, K.; Wu, H.; Gonda, S.

    2004-01-01

    Assessing the biological risks associated with exposure to the high-energy charged particles encountered in space is essential for the success of long-term space exploration. Although prokaryotic and eukaryotic cell models developed in our laboratory and others have advanced our understanding of many aspects of genotoxicity, in vitro models are needed to assess the risk to humans from space radiation insults. Such models must be representative of the cellular interactions present in tissues and capable of quantifying I genotoxic damage. Toward this overall goal, the objectives of this study were to examine the effect of the localized microenvironment of cells, cultured as either 2-dimensional (2D) monolayers or 3-dimensional (3D) aggregates, on the rate and type of genotoxic damage resulting from exposure to iron charged particles, a significant portion of space radiation. We used rodent transgenic cell lines containing 50-70 copies of a LacI transgene to provide the enhanced sensitivity required to quantify mutational frequency and type in the 1,100-bp LacI target as well as assessment of DNA,damage to the entire 45-kbp construct. Cultured cells were exposed to high-enerir on charged particles at Brookhaven National Laboratory s Alternating Gradient Synchrotron facility for a total dose of 0, 0.1, 0.25,0.5, 1.0, or 2.0 Gy and allowed to recover for 0, 1, or 7 days, after which mutational type and frequency were evaluated. The mutational frequency was found to be higher in 3D samples than in 2D samples at all radiation doses. Mutational frequency also was higher at 7 days after irradiation than immediately after exposure. DNA sequencing of the mutant targets revealed that deletional mutations contributed an increasingly high percentage (up to 27%) of all mutations in cells as the dose was increased from 0.5 to 2 Gy. Several mutants also showed large and complex deletions in multiple locations within the Lac1 target. However, no differences in mutational type were

  1. The alkaline comet assay used in evaluation of genotoxic damage of drinking water disinfection by-products (bromoform and chloroform

    Directory of Open Access Journals (Sweden)

    Messaouda Khallef

    2015-06-01

    Full Text Available The alkaline comet assay (pH 12.3 is a useful method for monitoring genotoxic effects of environmental pollutants in the root nuclei of Allium cepa and various plants; it allows the detection of single- and double-strand breaks, incomplete excision-repair sites and cross-links. It has been introduced to detect even small changes in DNA structure. It is a technically simple, highly sensitive, fast and economic test which detects in vitro and in vivo genotoxicity (DNA integrity and packing mode in any cell types examined, and requires just a few cells for its execution (Liman et al., 2011; Yıldız et al., 2009. Chloroform and bromoform are the most important trihalomethanes found in drinking water. Different concentrations of bromoform (25, 50, 75and 100µg/ml and chloroform (25, 50, 100 and 200 µg/ml were introduced to onion tuber roots. Distilled water was used as a negative control and methyl methansulfonate (MMS-10 µg/ml as positive control. All obtained data were subjected to statistical analyses by using SPSS 15.0 for Windows software. For comparison purposes, Duncan multiple range tests using one-way analysis of variance (ANOVA were employed and p<0.05 was accepted as the test of significance. Comet assay results showed that DNA damage was significant at p <0.05 for the different concentrations of chloroform and bromoform compared to the negative control which has a damage rate equal to 3.5 ± 0.7 and the positive control which has damage rate equal to 13.5 ± 2.12. The exposure of root tip cells to these disinfection by-products increases DNA damage. All concentrations examined in this study of bromoform and chloroform cause significant harm, which could be due to DNA damage induced by oxidative stress. The measurement of DNA damage in the nuclei of higher plant tissues is a new area of study with SCGE. This assay could be incorporated into in situ monitoring of atmosphere, water and soil: the comet assay allows a fast detection without

  2. The genotoxic effects of mobile phone waves on induction of chromosomal damages in embryos of Balb/C mice

    Directory of Open Access Journals (Sweden)

    Javad Baharara

    2010-12-01

    Full Text Available Background: In recent years, the widespread use of microwave producing instruments specially mobile phones; result in growing concern regarding the possible effects associated with these waves on human health. In the present study investigated the genotoxic effects of mobile phone radiation in adult mice (Balb/C and their embryos. Methods: In this experimental research pregnant mice were irradiated with mobile phone for 4 days during gestational period from 14th to 18th days of gestation for 6h/day from 9AM until 15PM. At the end of treatment period, euthanized the dams on day 18.5. Then embryos in 18.5th day of gestation were extracted. At first the morphology of embryos was studied, then documented their weight and CR length. For assessment of possible genetic damages in erythrocytes the blood was taken from their hearts and smear was prepared. Spleen tissue was prepared for histological studies. Smear was prepared from peripheral blood and bone marrow of mice and stained with May Grunowald and Gimsa. data were analyzed using t-test & ANOVA. Results: In experimental group, mobile phone radiation decreased embryos weight (P=0.04 but no change was observed in CR length. Megakaryocytes and red blood cells of spleen were significantly increased (P=0.002 and P<0.05, respectively. However, lymphocytes.numbers and micronucleus frequency in peripheral blood erythrocytes in experimental embryos and pregnant mice did not change. Interestingly, micronucleus frequency in polychromatic erythrocytes of bone marrow of pregnant mice was significantly increased (P <0.001.Conclusion: Mobile phone radiation (940 MHZ had genotoxic effects and increased micronucleus formation in polychromatic erythrocytes of bone marrow in pregnant mice.

  3. Internal distribution of uranium and associated genotoxic damages in the chronically exposed bivalve Corbicula fluminea

    Energy Technology Data Exchange (ETDEWEB)

    Simon, Olivier, E-mail: olivier.simon@irsn.fr [Laboratoire de Radioecologie et Ecotoxicologie, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat, 186 BP3, 13115 Saint Paul-Lez-Durance Cedex (France); Floriani, Magali; Cavalie, Isabelle; Camilleri, Virginie; Adam, Christelle; Gilbin, Rodolphe; Garnier-Laplace, Jacqueline [Laboratoire de Radioecologie et Ecotoxicologie, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat, 186 BP3, 13115 Saint Paul-Lez-Durance Cedex (France)

    2011-08-15

    Uranium (U) internal distribution and involved effects in the bivalve Corbicula fluminea have been studied after direct chronic exposure (90 d, 10 {mu}g.L-1). U distribution was assessed at the subcellular level (Metal Rich Granules -MRG-, pellets and cytosol fractions) in two main organs of the bivalve (gills and visceral mass). Micro-localisation was investigated by TEM-EDX analysis in the gills epithelium. DNA damage in gill and hemolymph samples was measured by the Comet assay. The 90-d exposure period led to a significant increase of U concentration in gills over time (x5) and a large U quantity in subcellular granules in gills. Finally, a significant increase (x2) in DNA damage was noted in exposed gills and haemocytes. This study shows that the accumulation levels and consequently the potential toxicity cannot be successfully predicted only on the basis of concentration in water or in tissues and subcellular fractions after chronic exposure. - Highlights: > Relevant information concerning the chronic impact of uranium on biota is scarce. > We study its biological speciation to explain bioavailability, accumulation, toxicity. > 80% of U accumulated was measured in the pellet fraction (organelles + granules/MRG). > Chronic exposure to U induced genetic damage in gill and haemolymph cells of the bivalve.

  4. Genotoxic damage in mine workers exposed to diesel exhaust, and the effects of glutathione transferase genotypes.

    Science.gov (United States)

    Knudsen, L E; Gaskell, M; Martin, E A; Poole, J; Scheepers, P T J; Jensen, A; Autrup, H; Farmer, P B

    2005-06-01

    This study was performed in an Estonian shale-oil mine with the purpose to develop and apply a number of biomarkers for occupational diesel-exhaust exposure monitoring. Increased breathing-zone exposures to exhaust from operators of diesel-powered trucks in the mine was confirmed in the environmental monitoring part of the study, showing a 7.5-fold higher exposure to particle-associated 1-nitropyrene (1-NP) in 50 underground workers compared with 42 surface workers [P.T.J. Scheepers, D. Coggon, L.E. Knudsen, R. Anzion, H. Autrup, S. Bogovski, R.P. Bos, D. Dahmann, P. Farmer, E.A. Martin, V. Micka, V. Muzyka, H.-G. Neumann, J. Poole, A. Schmidt-Ott, F. Seiler, J. Volf, I. Zwirner-Baier, Biomarkers for occupational diesel exhaust exposure monitoring (BIOMODEM)-a study in underground mining, Toxicol. Lett. 134 (2002) 305-317; P.T.J. Scheepers, V. Micka, V. Muzyka, R. Anzion, D. Dahmann, J. Poole, R.P. Bos, Exposure to dust and particle-associated 1-nitropyrene of drivers of diesel-powered equipment in underground mining, Ann. Occp. Hyg. 47 (2003) 379-388]. Analysis of DNA damage by the Comet assay on frozen blood samples was performed on the total study group and showed significantly higher levels (p=0.003) in underground workers (smokers) driving diesel-powered excavation machines (median 155 on a scale from 0 to 400, among 47 persons), compared with surface workers who smoked (median of 90, among 46 persons). The level of DNA damage in underground smokers was significantly higher (p=0.04) than in non-smokers. Samples from 2 of the 3 sampling weeks had significantly lower DNA damage compared with the third week, probably due to timely processing and freezing. These samples also showed significant differences (p<0.001) between underground workers (median 145, among 41 persons) and surface workers (median 60, among 30 persons). An HPLC method was developed for the analysis of (32)P-postlabelled 1-NP-DNA-adducts, and was applied to a sub-sample of 20 workers. No

  5. Genotoxic Evaluation of Mikania laevigata Extract on DNA Damage Caused by Acute Coal Dust Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Freitas, T.P.; Heuser, V.D.; Tavares, P.; Leffa, D.D.; da Silva, G.A.; Citadini-Zanette, V.; Romao, P.R.T.; Pinho, R.A.; Streck, E.L.; Andrade,V.M. [University of Extremo Catarinense, Criciuma, SC (Brazil)

    2009-06-15

    We report data on the possible antigenotoxic activity of Mikania laevigata extract (MLE) after acute intratracheal instillation of coal dust using the comet assay in peripheral blood, bone marrow, and liver cells and the micronucleus test in peripheral blood of Wistar rats. The animals were pretreated for 2 weeks with saline solution (groups 1 and 2) or MLE (100 mg/kg) (groups 3 and 4). On day 15, the animals were anesthetized with ketamine (80 mg/kg) and xylazine (20 mg/kg), and gross mineral coal dust (3 mg/0.3 mL saline) (groups 2 and 4) or saline solution (0.3 mL) (groups 1 and 3) was administered directly in the lung by intratracheal administration. Fifteen days after coal dust or saline instillation, the animals were sacrificed, and the femur, liver, and peripheral blood were removed. The results showed a general increase in the DNA damage values at 8 hours for all treatment groups, probably related to surgical procedures that had stressed the animals. Also, liver cells from rats treated with coal dust, pretreated or not with MLE, showed statistically higher comet assay values compared to the control group at 14 days after exposure. These results could be expected because the liver metabolizes a variety of organic compounds to more polar by-products. On the other hand, the micronucleus assay results did not show significant differences among groups. Therefore, our data do not support the antimutagenic activity of M. laevigata as a modulator of DNA damage after acute coal dust instillation.

  6. Biomarkers of environmental genotoxicity: comparison of genetic damage induced in Trad-SH cells and human lymphocytes

    International Nuclear Information System (INIS)

    The report presents some of the results of genotoxicity of the environmental agents studied in somatic cells of Tradescantia and show similarity between responses of the Tradescantia stamen hair cells (Trad-SH) and human blood cells to the physical and chemical mutagens. In the studies in vitro chromosome aberrations (CA) and sister chromatid exchanges (SCE) were applied to evaluate genotoxicity of pesticides. For comparison of genotoxic effectiveness of agrochemicals with other chemicals, there are also presented results of the genotoxicity of well-known mutagens (EMS, X-rays). The results confirm that in the environment a chemical pollution might cause higher genetic risk than radiation. Trad-SH assay was applied for in situ monitoring of the ambient air mutagenicity caused by benzene and petroleum associated compounds. The studies showed that gene mutation frequencies were slightly dependent on the distance from the petroleum work center. Results of measures of the cell cycle factor have shown also that the chemical pollutants in the air played also an important role in physiological cellular processes. The similarity of the Trad-SH and human blood cells responses to the physical and chemical mutagens showed that the gene mutations in Tradescantia present a simple and sensitive model, which can be very useful in biological monitoring

  7. In Vivo Effects of Vanadium Pentoxide and Antioxidants (Ascorbic Acid and Alpha-Tocopherol) on Apoptotic, Cytotoxic, and Genotoxic Damage in Peripheral Blood of Mice

    Science.gov (United States)

    García-Rodríguez, María del Carmen; Hernández-Cortés, Lourdes Montserrat; Altamirano-Lozano, Mario Agustín

    2016-01-01

    This study was conducted to investigate the effects of vanadium pentoxide (V2O5), ascorbic acid (AA), and alpha-tocopherol (α-TOH) on apoptotic, cytotoxic, and genotoxic activity. Groups of five Hsd:ICR mice were treated with the following: (a) vehicle, distilled water; (b) vehicle, corn oil; (c) AA, 100 mg/kg intraperitoneally (ip); (d) α-TOH, 20 mg/kg by gavage; (e) V2O5, 40 mg/kg by ip injection; (f) AA + V2O5; and (g) α-TOH + V2O5. Genotoxic damage was evaluated by examining micronucleated polychromatic erythrocytes (MN-PCE) obtained from the caudal vein at 0, 24, 48, and 72 h after treatments. Induction of apoptosis and cell viability were assessed at 48 h after treatment in nucleated cells of peripheral blood. Treatment with AA alone reduced basal MN-PCE, while V2O5 treatment marginally increased MN-PCE at all times after injection. Antioxidants treatments prior to V2O5 administration decreased MN-PCE compared to the V2O5 group, with the most significant effect in the AA + V2O5 group. The apoptotic cells increased with all treatments, suggesting that this process may contribute to the elimination of the cells with V2O5-induced DNA damage (MN-PCE). The necrotic cells only increased in the V2O5 group. Therefore, antioxidants such as AA and α-TOH can be used effectively to protect or reduce the genotoxic effects induced by vanadium compounds like V2O5. PMID:27413422

  8. Long-term exposure of A549 cells to titanium dioxide nanoparticles induces DNA damage and sensitizes cells towards genotoxic agents.

    Science.gov (United States)

    Armand, Lucie; Tarantini, Adeline; Beal, David; Biola-Clier, Mathilde; Bobyk, Laure; Sorieul, Sephanie; Pernet-Gallay, Karin; Marie-Desvergne, Caroline; Lynch, Iseult; Herlin-Boime, Nathalie; Carriere, Marie

    2016-09-01

    Titanium dioxide nanoparticles (TiO2-NPs) are one of the most produced NPs in the world. Their toxicity has been studied for a decade using acute exposure scenarios, i.e. high exposure concentrations and short exposure times. In the present study, we evaluated their genotoxic impact using long-term and low concentration exposure conditions. A549 alveolar epithelial cells were continuously exposed to 1-50 μg/mL TiO2-NPs, 86% anatase/14% rutile, 24 ± 6 nm average primary diameter, for up to two months. Their cytotoxicity, oxidative potential and intracellular accumulation were evaluated using MTT assay and reactive oxygen species measurement, transmission electron microscopy observation, micro-particle-induced X-ray emission and inductively-coupled plasma mass spectroscopy. Genotoxic impact was assessed using alkaline and Fpg-modified comet assay, immunostaining of 53BP1 foci and the cytokinesis-blocked micronucleus assay. Finally, we evaluated the impact of a subsequent exposure of these cells to the alkylating agent methyl methanesulfonate. We demonstrate that long-term exposure to TiO2-NPs does not affect cell viability but causes DNA damage, particularly oxidative damage to DNA and increased 53BP1 foci counts, correlated with increased intracellular accumulation of NPs. In addition, exposure over 2 months causes cellular responses suggestive of adaptation, characterized by decreased proliferation rate and stabilization of TiO2-NP intracellular accumulation, as well as sensitization to MMS. Taken together, these data underline the genotoxic impact and sensitization effect of long-term exposure of lung alveolar epithelial cells to low levels of TiO2-NPs. PMID:26785166

  9. The genotoxic effects of mobile phone waves on induction of chromosomal damages in embryos of Balb/C mice

    OpenAIRE

    Javad Baharara; Farhang Hadad; Mohammad-Ali Shariatzade; Mariam Amirahmadi

    2010-01-01

    Background: In recent years, the widespread use of microwave producing instruments specially mobile phones; result in growing concern regarding the possible effects associated with these waves on human health. In the present study investigated the genotoxic effects of mobile phone radiation in adult mice (Balb/C) and their embryos. Methods: In this experimental research pregnant mice were irradiated with mobile phone for 4 days during gestational period from 14th to 18th days of gestation for...

  10. Evaluation of the Genotoxic Potential against H2O2-Radical-Mediated DNA Damage and Acute Oral Toxicity of Standardized Extract of Polyalthia longifolia Leaf

    Directory of Open Access Journals (Sweden)

    Subramanion L. Jothy

    2013-01-01

    Full Text Available Medicinal plants have been used in medicoculturally diverse countries around the world, where it is a part of a time-honoured tradition that is respected even today. Polyalthia longifolia leaf extract has been previously reported as an efficient antioxidant in vitro. Hence, the genotoxic effects of P. longifolia leaf were investigated by using plasmid relation, comet, and Allium cepa assay. In the presence of  ∙OH radicals, the DNA in supercoil was start nicked into open circular form, which is the product of the single-stranded cleavage of supercoil DNA and quantified as fragmented separate bands on agarose gel in plasmid relation assay. In the plasmid relation and comet assay, the P. longifolia leaf extract exhibited strong inhibitory effects against H2O2-mediated DNA damage. A dose-dependent increase of chromosome aberrations was also observed in the Allium cepa assay. The abnormalities scored were stickiness, c-mitosis, bridges, and vagrant chromosomes. Micronucleated cells were also observed at the interphase. The results of Allium cepa assay confirmed that the methanol extracts of P. longifolia exerted no significant genotoxic or mitodepressive effects at 100 μg/mL. Thus, this study demonstrated that P. longifolia leaf extract has a beneficial effect against oxidative DNA damage. This experiment is the first report for the protective effect of P. longifolia on DNA damage-induced by hydroxyl radicals. Additionally in acute oral toxicity study, female rats were treated at 5000 mg/kg body weight of P. longifolia leaf extract and observed for signs of toxicity for 14 days. P. longifolia leaf extract did not produce any treatment-related toxic effects in rats.

  11. Anti-genotoxic effect of naringin against bleomycin-induced genomic damage in human lymphocytes in vitro.

    Science.gov (United States)

    Yilmaz, Dilek; Teksoy, Ozgun; Bilaloglu, Rahmi; Çinkilic, Nilufer

    2016-01-01

    Naringin is a flavonoid found in grapefruit and other citrus fruits that shows antioxidant activity. The aim of the present study was to determine the anti-genotoxic and protective effects of naringin on the chemotherapeutic/radiomimetic agent bleomycin (BLM) in human blood lymphocyte cultures in vitro using micronucleus test and chromosomal aberrations (CA) assay. We tested the three doses of naringin (1, 2, 3 µg/mL) and a single dose of BLM (20 µg/mL). BLM significantly increased the total CAs and micronucleus frequency at a concentration of 20 µg/mL. Naringin did not show any toxicity in doses of 1, 2, and 3 µg/mL. Combined treatments of BLM and naringin (2 and 3 µg/mL) significantly reduced micronucleus formation. Naringin dose-dependently decreased the total chromosome aberrations frequency induced by BLM. These results indicate that naringin could prevent BLM (20 µg/mL)-induced genotoxicity. PMID:25941869

  12. Genotoxicity of swine effluents.

    Science.gov (United States)

    Techio, V H; Stolberg, J; Kunz, A; Zanin, E; Perdomo, C C

    2011-01-01

    This study aimed at the investigation of genotoxic effects of swine effluents from different stages of a treatment system for swine wastes through bioassay of stamen hairs and micronuclei in Tradescantia (clone BNL 4430). No significant differences (p≥0.05) regarding the genic mutations were found in the bioassay of stamen hairs, independently of the effluent analysed. For the genotoxicity test with micronuclei, the plants exposed to raw wastes, to sludge, and to effluent of the biodigester have presented higher rates of chromosomal damages (micronuclei), with significant differences in relation to the control group and other effluent of the waste treatment system (p≤0.05). The association between the chemical parameters and the genotoxicity data have shown that the variables COD and TKN have presented significant correlation (p≤0.05) with the number of mutagenic events in the tetrads.

  13. Genotoxic Damage in vivo, Susceptibility to UVC and X-Rays, and Repair Efficiency in vitro Lymphocytes from Referent and Occupational Exposed to Mercury Vapours Group

    International Nuclear Information System (INIS)

    For years mercury has been considered to be dangerous for human health. It was shown in vitro studies that mercury ions produce various types of DNA damage: single strand breaks as well as alkali labile lesions. The aim of this study was to compare levels of the DNA damage and cytogenetic damage induced in vivo, DNA's susceptibility to radiation, as well as repair capabilities of DNA damage induced in vitro by UV-exposure or X-rays, in lymphocytes from unexposed donors and from persons occupationally exposed to mercury vapours. In order to estimate cytogenetic damage, the analysis of sister chromatid exchange frequency (SCE) was used, while to detect DNA damage alkaline version of the single cell gel electrophoresis (SCGE) was applied. To analyse in vitro susceptibility of cells to genotoxic factors such as UV-C or X-rays, lymphocytes were exposed to 6 J/m2 of UV or irradiated with 2 Gy of X-rays. After exposure the cells were incubated for 2 hours with or without the presence of phytohemagglutinin (agent stimulating cell divisions). In the present study, results do not show any statistically significant differences between the examined groups, either in the levels of DNA damage of untreated lymphocytes or in the sister chromatid exchanges. Neither the levels of DNA damage detected in lymphocytes after UV exposure and 2 h incubation, without or in the presence of a cell- division stimulating agent, nor the repair efficiencies of the DNA damage induced by UV exposure, differed significantly between the unexposed group and that occupationally exposed to mercury vapours. Statistically significant higher levels of DNA damage measured in X-ray-irradiated lymphocytes, without incubation and after 2 hours of incubation, with or without the presence of phytohemagglutinin, were observed in the group exposed to mercury vapours. So, donors exposed to mercury vapours have shown a statistically lower repair efficiency of X-ray-induced DNA damage both in non- stimulated

  14. Genotoxicity of phthalates.

    Science.gov (United States)

    Erkekoglu, Pınar; Kocer-Gumusel, Belma

    2014-12-01

    Many of the environmental, occupational and industrial chemicals are able to generate reactive oxygen species (ROS) and cause oxidative stress. ROS may lead to genotoxicity, which is suggested to contribute to the pathophysiology of many human diseases, including inflammatory diseases and cancer. Phthalates are ubiquitous environmental chemicals and are well-known peroxisome proliferators (PPs) and endocrine disruptors. Several in vivo and in vitro studies have been conducted concerning the carcinogenic and mutagenic effects of phthalates. Di(2-ethylhexyl)-phthalate (DEHP) and several other phthalates are shown to be hepatocarcinogenic in rodents. The underlying factor in the hepatocarcinogenesis is suggested to be their ability to generate ROS and cause genotoxicity. Several methods, including chromosomal aberration test, Ames test, micronucleus assay and hypoxanthine guanine phosphoribosyl transferase (HPRT) mutation test and Comet assay, have been used to determine genotoxic properties of phthalates. Comet assay has been an important tool in the measurement of the genotoxic potential of many chemicals, including phthalates. In this review, we will mainly focus on the studies, which were conducted on the DNA damage caused by different phthalate esters and protection studies against the genotoxicity of these chemicals.

  15. Dermal exposure to the herbicide-paraquat results in genotoxic and cytotoxic damage to germ cells in the male rat.

    Science.gov (United States)

    D'Souza, U J A; Narayana, K; Zain, A; Raju, S; Nizam, H M; Noriah, O

    2006-02-01

    The effects of exposure to low doses of paraquat, a herbicide, via the dermal route were studied on the spermatozoa of Sprague-Dawley rats. Paraquat (1, 1'-dimethyl-4, 4'-bipyridinium dichloride) was administered once a day for five days, at intervals of 24 h at 0, 6, 15 and 30 mg/kg, and the rats were sacrificed on days 7, 14, 28, and 42 after the last exposure. The sperm suspensions were obtained by mincing the caudae epididymes and ductus deferens for the purpose of performing a sperm morphology test, sperm count and analysis of sperm mortality and sperm motility, as per the standard procedures. The sperm count was decreased (p < 0.05) only on days 7 and 14 but sperm abnormalities increased on all days (p < 0.05). Sperm mortality increased at higher dose-levels (p < 0.05) except on day 42, and motility was affected by 30 mg/kg only on day 42. In conclusion, paraquat is a genotoxic and cytotoxic agent to germ cells in the male rat. PMID:16783728

  16. The Anti-Genotoxic Effect of Taurine on Aluminum Sulphate-Induced DNA Damage in Human Peripheral Lymphocytes

    OpenAIRE

    Türkez, Hasan; Geyikoğlu, Fatime

    2010-01-01

    Aluminum sulphate Al2(SO4)3 is commonly used as a coagulant in the purification of drinking water in many regions of the world. Aluminum (Al) is also involved in several pharmaceutical and cosmetic products. However, Al is suspected to cause serious disorders such as Alzheimer's by oxidative DNA damage. On the other hand, taurine (TA) is an amino acid found in mammalian tissues and it has been suggested to play a role in the defense against cellular damage. The objective of this study was to ...

  17. Progression of DNA damage induced by a glyphosate-based herbicide in fish (Anguilla anguilla) upon exposure and post-exposure periods--insights into the mechanisms of genotoxicity and DNA repair.

    Science.gov (United States)

    Marques, Ana; Guilherme, Sofia; Gaivão, Isabel; Santos, Maria Ana; Pacheco, Mário

    2014-11-01

    Roundup® is a glyphosate-based herbicide widely used with both agricultural and non-agricultural purposes, which has been demonstrated to represent a risk to non-target aquatic organisms, namely fish. Among the described effects to fish, genotoxicity has been pointed out as one of the most hazardous. However, the genotoxic mechanisms of Roundup® as well as the involvement of the oxidative DNA damage repair system are not entirely understood. Hence, this work aimed to improve the knowledge on the progression of DNA damage upon short-term exposure (3 days) and post-exposure (1-14 days) periods in association with DNA repair processes in Anguilla anguilla exposed to Roundup® (58 and 116 μg L⁻¹). DNA damage in hepatic cells was evaluated by the comet assay improved with the DNA-lesion specific endonucleases FPG and EndoIII. In order to evaluate the oxidative DNA damage repair ability, an in vitro base excision repair (BER) assay was performed, testing hepatic subcellular extracts. Besides the confirmation of the genotoxic potential of this herbicide, oxidative damage was implicit as an important mechanism of genetic damage, which showed to be transient, since DNA integrity returned to the control levels on the first day after cessation of exposure. An increased capacity to repair oxidative DNA damage emerging in the post-exposure period revealed to be a crucial pathway for the A. anguilla recovery; nevertheless, DNA repair machinery showed to be susceptible to inhibitory actions during the exposure period, disclosing another facet of the risk associated with the tested agrochemical.

  18. Inhibition of fried meat-induced rectal DNA damage and altered systemic genotoxicity in humans by crucifera, chlorophyllin, and yogurt

    Science.gov (United States)

    Dietary exposures implicated as reducing or causing risk for colorectal cancer may reduce or cause DNA damage in colon tissue; however, no one has assessed this hypothesis directly in humans. Thus, we enrolled 16 healthy volunteers in a 4-week controlled feeding study where 8 sub...

  19. Inhibition of fried meat-induced colorectal DNA damage and altered systemic genotoxicity in humans by crucifera, chlorophyllin, and yogurt.

    Directory of Open Access Journals (Sweden)

    Daniel T Shaughnessy

    Full Text Available Dietary exposures implicated as reducing or causing risk for colorectal cancer may reduce or cause DNA damage in colon tissue; however, no one has assessed this hypothesis directly in humans. Thus, we enrolled 16 healthy volunteers in a 4-week controlled feeding study where 8 subjects were randomly assigned to dietary regimens containing meat cooked at either low (100°C or high temperature (250°C, each for 2 weeks in a crossover design. The other 8 subjects were randomly assigned to dietary regimens containing the high-temperature meat diet alone or in combination with 3 putative mutagen inhibitors: cruciferous vegetables, yogurt, and chlorophyllin tablets, also in a crossover design. Subjects were nonsmokers, at least 18 years old, and not currently taking prescription drugs or antibiotics. We used the Salmonella assay to analyze the meat, urine, and feces for mutagenicity, and the comet assay to analyze rectal biopsies and peripheral blood lymphocytes for DNA damage. Low-temperature meat had undetectable levels of heterocyclic amines (HCAs and was not mutagenic, whereas high-temperature meat had high HCA levels and was highly mutagenic. The high-temperature meat diet increased the mutagenicity of hydrolyzed urine and feces compared to the low-temperature meat diet. The mutagenicity of hydrolyzed urine was increased nearly twofold by the inhibitor diet, indicating that the inhibitors enhanced conjugation. Inhibitors decreased significantly the mutagenicity of un-hydrolyzed and hydrolyzed feces. The diets did not alter the levels of DNA damage in non-target white blood cells, but the inhibitor diet decreased nearly twofold the DNA damage in target colorectal cells. To our knowledge, this is the first demonstration that dietary factors can reduce DNA damage in the target tissue of fried-meat associated carcinogenesis.ClinicalTrials.gov NCT00340743.

  20. Genotoxic and cytotoxic damage by the therapeutic radiopharmaceutical [166Dy]Dy/166Ho-EDTMP as in vivo generator system

    International Nuclear Information System (INIS)

    In patients with leukemias and multiple myeloma, the cure can be obtained to inclination of a bone marrow transplant (m.o.), for that which one is used a combination of external radiotherapy and chemotherapy with the consequent toxicity to healthy organs. The complex [166Dy]Dy/166Ho-ethylenediaminetetramethylenephosphonate ([166Dy]Dy/166Ho-EDTMP) it forms a generator system in vivo stable with bony selective likeness in mice therefore, this it could work as a therapeutic radiopharmaceutical for bone marrow ablation. The objective of this original work was to determine the genotoxic and cytotoxic damage produced by the [166Dy]Dy/166Ho-EDTMP like a generator system in vivo by means of the reticulocytes reduction (RET) and micronucleus elevation in reticulocytes (RET-MN) in peripheral blood and to evaluate its myeloablative potential for histopathologic studies. It was irradiated 166Dy2O3 enriched and it was add in form 166DyCI3 to the EDTMP in a softening media of phosphates (pH 8), the optimal molar relationship 166Dy: EDTMP was 1.7:1 and the radiochemical purity was evaluated by ITLC. The Dy:EDTMP complexes, non radioactive, its were prepared in the same way with non irradiated dysprosium oxide. A group of BALB/c mice was injected intraperitoneally with the radiopharmaceutical and two groups of control mice were injected with the non radioactive complex and with sodium chloride 0.9% respectively. Before injecting each one of the solutions it was take a basal sample of peripheral blood of the mouse tail and each 48 h post-injection during 12 d. The animals were sacrificed to obtain the organs of interest and to determine the radioactivity in each one. The femur was used for the histopathologic studies. The quantification of the frequency of RET and RET-MN was carried out by flow cytometry of the sanguine samples and the Monte Carlo code MCNP4B for the dosimetry calculations was used. The radiochemical purity was 99% and in average the specific activity was of 1

  1. Genotoxicity of Tri- and Hexavalent Chromium Compounds In Vivo and Their Modes of Action on DNA Damage In Vitro

    OpenAIRE

    Zhijia Fang; Min Zhao; Hong Zhen; Lifeng Chen; Ping Shi; Zhiwei Huang

    2014-01-01

    Chromium occurs mostly in tri- and hexavalent states in the environment. Hexavalent chromium [Cr(VI)] compounds are extensively used in diverse industries, and trivalent chromium [Cr(III)] salts are used as micronutrients and dietary supplements. In the present work, we report that they both induce genetic mutations in yeast cells. They both also cause DNA damage in both yeast and Jurkat cells and the effect of Cr(III) is greater than that of Cr(VI). We further show that Cr(III) and Cr(VI) ca...

  2. Is tetrachloroethylene genotoxic or not?

    Science.gov (United States)

    Lovell, David

    2010-09-01

    A recent study published in Mutagenesis, in which the ability of tetrachloroethylene to induce DNA damage, detected by the alkaline comet assay, in mouse tissues (liver and kidney) was examined, has resulted in different interpretations of the data for liver as either positive or negative for genotoxicity. Here, I discuss the statistical approaches used and comment on the different conclusions reached.

  3. Genotoxicity assessment in Eisenia andrei coelomocytes: a study of the induction of DNA damage and micronuclei in earthworms exposed to B[a]P- and TCDD-spiked soils.

    Science.gov (United States)

    Sforzini, Susanna; Boeri, Marta; Dagnino, Alessandro; Oliveri, Laura; Bolognesi, Claudia; Viarengo, Aldo

    2012-07-01

    Earthworms are useful indicators of soil quality and are widely used as model organisms in terrestrial ecotoxicology. The assessment of genotoxic effects caused by environmental pollutants is of great concern because of their relevance in carcinogenesis. In this work, the earthworm Eisenia andrei was exposed for 10 and 28 days to artificial standard soil contaminated with environmentally relevant concentrations of benzo[a]pyrene (B[a]P) (0.1, 10, 50ppm) and 2,3,7,8-tetrachloro-dibenzo-para-dioxin (TCDD) (1×10(-5), 1×10(-4), 2×10(-3)ppm). Micronucleus (MNi) induction was evaluated in earthworm coelomocytes after DNA staining with the fluorescent dye DAPI. In the same cells, the DNA damage was assessed by means of the alkaline comet assay. Induction of MNi in coelomocytes, identified according to standard criteria, was demonstrated. B[a]P exposure for 10 and 28 days induced a significant increase in MNi frequency. In TCDD-treated earthworms, a significant effect on chromosomal damage was observed at all the concentrations used; surprisingly, greater effects were induced in animals exposed to the lowest concentration (1×10(-5)ppm). The data of the comet assay revealed a significant increase in the level of DNA damage in coelomocytes of earthworms exposed for 10 and 28 days to the different concentrations of B[a]P and TCDD. The results show that the comet and MN assays were able to reveal genotoxic effects in earthworms exposed even to the lowest concentrations of both chemicals tested here. The combined application in E. andrei of the comet assay and the micronucleus test, which reflect different biological mechanisms, may be suggested to identify genotoxic effects induced in these invertebrates by environmental contaminants in terrestrial ecosystems. PMID:22459015

  4. Monitoring of genotoxic effects in lymphocytes of people exposed to pesticides

    International Nuclear Information System (INIS)

    The aim of this study was to assess the potential genotoxic risk of occupational exposure to pesticides. The DNA damage and the repair capacities of lymphocytes, in four groups of the people of various countries were assessed by the use of single cell gel electrophoresis (SCGE) also known as the Comet assay. The results from the analysis performed in the Spanish group are presented in this paper. Statistical analysis of the results shows a slightly higher level of the DNA damage in the untreated lymphocytes of donors from the group exposed to pesticides; however, only for donors below 30 years old are these differences significant (p<0.05). Although, comparison of the efficiency of the UV-C induced dimmers excision process did not indicate differences between exposed and referent groups, though lymphocytes for donors exposed to pesticides have shown a statistically lower repair rate (p<0.01) than lymphocytes from the unexposed group. (author)

  5. Is the Comet Assay a Sensitive Procedure for Detecting Genotoxicity?

    OpenAIRE

    Sasaki, Yu F.; Satomi Kawaguchi; Takanori Nakamura; Gisho Honda; Ayumi Yamamoto

    2010-01-01

    Although the Comet assay, a procedure for quantitating DNA damage in mammalian cells, is considered sensitive, it has never been ascertained that its sensitivity is higher than the sensitivity of other genotoxicity assays in mammalian cells. To determine whether the power of the Comet assay to detect a low level of genotoxic potential is superior to those of other genotoxicity assays in mammalian cells, we compared the results of Comet assay with those of micronucleus test (MN test). WTK1 hum...

  6. Genotoxicity of titanium dioxide nanoparticles

    Directory of Open Access Journals (Sweden)

    Tao Chen

    2014-03-01

    Full Text Available Titanium dioxide nanoparticles (TiO2-NPs, <100 nm are increasingly being used in pharmaceuticals and cosmetics due to the unique properties derived from their small sizes. However, their large surface-area to mass ratio and high redox potential may negatively impact human health and the environment. TiO2-NPs can cause inflammation, pulmonary damage, fibrosis, and lung tumors and they are possibly carcinogenic to humans. Because cancer is a disease involving mutation, there are a large number of studies on the genotoxicity of TiO2-NPs. In this article, we review the results that have been reported in the literature, with a focus on data generated from the standard genotoxicity assays. The data include genotoxicity results from the Ames test, in vitro and in vivo Comet assay, in vitro and in vivo micronucleus assay, sister chromatid exchange assay, mammalian cell hypoxanthine-guanine phosphoribosyl transferase gene assay, the wing somatic mutation and recombination assay, and the mouse phosphatidylinositol glycan, class A gene assay. Inconsistent results have been found in these assays, with both positive and negative responses being reported. The in vitro systems for assessing the genotoxicity of TiO2-NPs have generated a greater number of positive results than the in vivo systems, and tests for DNA and chromosome damage have produced more positive results than the assays measuring gene mutation. Nearly all tests for measuring the mutagenicity of TiO2-NPs were negative. The current data indicate that the genotoxicity of TiO2-NPs is mediated mainly through the generation of oxidative stress in cells.

  7. Detection of acute and chronic genotoxic damage in an occupationally-exposed population Detección del daño genotóxico agudo y crónico en una población

    Directory of Open Access Journals (Sweden)

    Natalia Andrea Giraldo Solano

    2003-03-01

    Full Text Available Worldwide studies in people occupationally exposed to genotoxic agents have shown a strong correlation of the exposition with cancer incidence and reproductive dysfunctions. This research evaluated, in laboratory personnel at the Universidad Nacional, Medellín, Colombia, the effect of exposition to potentially genotoxic agents, by means of sister chromatids interchange tests (SCI and electrophoresis in single cells gel (comet assay. Standardization of methodological tools to quantify the damage produced by exposition to potentially genotoxic agents was achieved, in order to implement them in occupational health monitoring programs. Evaluation was carried out in two populations, exposed and control, using paired samples. Age, sex and habits were used as criterions for pairing. Comet assay showed punctual damage in the exposed population, while SCI test did not reveal chronic damage. On the other hand, neither habits nor sex showed relation with SCI index, but age did. The usefulness of the comet assay to measure the effect of punctual expositions, and that of SCI as an excellent test to quantify the effect of chronic expositions, makes them indispensable as part of the battery used in genotoxic monitoring studies. As part of the benefits of this research, infrastructure was adapted and some personnel was qualified to carry out occupational health genotoxic monitoring, with the aim of extending this service to the University community and to the private and public sectors. En el àmbito mundial se ha encontrado una fuerte relación entre la exposición a agentes genotóxicos y la incidencia de cáncer y problemas reproductivos, en personal ocupacionalmente expuesto. En el presente trabajo se evaluó, en personal vinculado a los laboratorios de la Universidad Nacional de Colombia, sede Medellín, el efecto de la exposición a agentes potencialmente genotóxicos, mediante las pruebas de intercambio de cromátides hermanas (ICH y la electroforesis

  8. Cell-Based Genotoxicity Testing

    Science.gov (United States)

    Reifferscheid, Georg; Buchinger, Sebastian

    Genotoxicity test systems that are based on bacteria display an important role in the detection and assessment of DNA damaging chemicals. They belong to the basic line of test systems due to their easy realization, rapidness, broad applicability, high sensitivity and good reproducibility. Since the development of the Salmonella microsomal mutagenicity assay by Ames and coworkers in the early 1970s, significant development in bacterial genotoxicity assays was achieved and is still a subject matter of research. The basic principle of the mutagenicity assay is a reversion of a growth inhibited bacterial strain, e.g., due to auxotrophy, back to a fast growing phenotype (regain of prototrophy). Deeper knowledge of the ­mutation events allows a mechanistic understanding of the induced DNA-damage by the utilization of base specific tester strains. Collections of such specific tester strains were extended by genetic engineering. Beside the reversion assays, test systems utilizing the bacterial SOS-response were invented. These methods are based on the fusion of various SOS-responsive promoters with a broad variety of reporter genes facilitating numerous methods of signal detection. A very important aspect of genotoxicity testing is the bioactivation of ­xenobiotics to DNA-damaging compounds. Most widely used is the extracellular metabolic activation by making use of rodent liver homogenates. Again, genetic engineering allows the construction of highly sophisticated bacterial tester strains with significantly enhanced sensitivity due to overexpression of enzymes that are involved in the metabolism of xenobiotics. This provides mechanistic insights into the toxification and detoxification pathways of xenobiotics and helps explaining the chemical nature of hazardous substances in unknown mixtures. In summary, beginning with "natural" tester strains the rational design of bacteria led to highly specific and sensitive tools for a rapid, reliable and cost effective ­genotoxicity

  9. Assessment of isorhamnetin 3-O-neohesperidoside from Acacia salicina: protective effects toward oxidation damage and genotoxicity induced by aflatoxin B1 and nifuroxazide.

    Science.gov (United States)

    Bouhlel, Ines; Limem, Ilef; Skandrani, Ines; Nefatti, Aicha; Ghedira, Kamel; Dijoux-Franca, Marie-Genevieve; Leila, Chekir-Ghedira

    2010-08-01

    Antioxidant activity of isorhamnetin 3-O-neohesperidoside, isolated from the leaves of Acacia salicina, was determined by the ability of this compound to inhibit xanthine oxidase activity and to scavenge the free radical 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS(.-)) diammonium salt. Antigenotoxic activity was assessed using the SOS chromotest assay. This compound has the ability to scavenge the ABTS(.+) radical by a hydrogen donating mechanism. We also envisaged the study of the antioxidant effect of this compound by the enzymatic xanthine/xanthine oxidase (X/XOD) assay. Results indicated that isorhamnetin 3-O-neohesperidoside was a potent inhibitor of xanthine oxidase and superoxide anion scavengers. Moreover, this compound induced an inhibitory activity against nifuroxazide and aflatoxine B1 (AFB1) induced genotoxicity. Taken together, these observations provide evidence that isorhamnetin 3-O-neohesperidoside isolated from the leaves of A. salicina is able to protect cells against the consequences of oxidative stress. PMID:20809543

  10. Insights into genotoxic effects of electromagnetic fields

    OpenAIRE

    Focke, Frauke

    2008-01-01

    The increasing use of appliances, which generate electromagnetic fields (EMFs), has provoked public concern about their safety. Scientific research into possible health effects however produced conflicting results. One of the open questions is whether or not EMF exposure has genotoxic effects. Therefore, the main objective of my thesis was to investigate DNA damage formation and repair, cell cycle progression, apoptosis and DNA damage signalling in cultured human cells under EM...

  11. Environmental genotoxicity: Probing the underlying mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Shugart, L. [Oak Ridge National Lab., TN (United States); Theodorakis, C. [Tennessee Univ., Knoxville, TN (United States)

    1993-12-31

    Environmental pollution is a complex issue because of the diversity of anthropogenic agents, both chemical and physical, that have been detected and catalogued. The consequences to biota from exposure to genotoxic agents present an additional problem because of the potential for these agents to produce adverse change at the cellular and organismal levels. Past studies in genetic toxicology at the Oak Ridge National Laboratory have focused on structural damage to the DNA of environmental species that may occur after exposure to genotoxic agents and the use of this information to document exposure and to monitor remediation. In an effort to predict effects at the population, community and ecosystem levels, current studies in genetic ecotoxicology are attempting to characterize the biological mechanisms at the gene level that regulate and limit the response of an individual organism to genotoxic factors in their environment.

  12. Human genotoxic study carried out two years after oil exposure during the clean-up activities using two different biomarkers.

    NARCIS (Netherlands)

    Biern, G.; Giraldo, J.; Zock, J.P.; Monyarch, G.; Espinosa, A.; Rodríguez-Trigo, G.; Gomez, F.; Pozo-Rodríguez, F.; Barberà, J.A.; Fuster, C.

    2015-01-01

    Micronuclei, comet and chromosome alterations assays are the most widely used biomarkers for determining the genotoxic damage in a population exposed to genotoxic chemicals. While chromosome alterations are an excellent biomarker to detect short- and long-term genotoxic effects, the comet assay only

  13. Genotoxic sensitivity of the developing hematopoietic system.

    Science.gov (United States)

    Udroiu, Ion; Sgura, Antonella

    2016-01-01

    Genotoxic sensitivity seems to vary during ontogenetic development. Animal studies have shown that the spontaneous mutation rate is higher during pregnancy and infancy than in adulthood. Human and animal studies have found higher levels of DNA damage and mutations induced by mutagens in fetuses/newborns than in adults. This greater susceptibility could be due to reduced DNA repair capacity. In fact, several studies indicated that some DNA repair pathways seem to be deficient during ontogenesis. This has been demonstrated also in murine hematopoietic stem cells. Genotoxicity in the hematopoietic system has been widely studied for several reasons: it is easy to assess, deals with populations cycling also in the adults and may be relevant for leukemogenesis. Reviewing the literature concerning the application of the micronucleus test (a validated assay to assess genotoxicity) in fetus/newborns and adults, we found that the former show almost always higher values than the latter, both in animals treated with genotoxic substances and in those untreated. Therefore, we draw the conclusion that the genotoxic sensitivity of the hematopoietic system is more pronounced during fetal life and decreases during ontogenic development. PMID:27036061

  14. Modulation of Tinospora rumphii and Zinc Salt on DNA Damage in Quinoline-Induced Genotoxicity and Hepatotoxicity in Male Albino Mice

    OpenAIRE

    Roger Salvacion Tan; Bajo, Lydia M.

    2014-01-01

    Tinospora rumphii (T. rumphii) is a folkloric medicinal plant that is widely distributed in Asia and Africa. It has been widely used by locals to treat many diseases including jaundice, which is a manifestation of liver damage. We investigated the action of T. rumphii crude extract together with zinc sulphate, a known tumor modulator, on hepatic injuries induced by intraperitoneal (i.p) injections of quinoline on albino mice. The hepatotoxic effect was assessed by bilirubin concentration in t...

  15. Bixin protects hepatocytes against 1,2-dimethylhydrazine-induced genotoxicity but does not suppress DNA damage and pre-neoplastic lesions in the colon of Wistar rats.

    Science.gov (United States)

    de Oliveira, Pollyanna Francielli; de Andrade, Kelly Jacqueline Barbosa; Paula, Marcela Cristina Ferreira; Oliveira Acésio, Nathália; da Silva Moraes, Thais; Borges, Priscilla Scalon Freitas; Barcelos, Gustavo Rafael Mazzaron; Tavares, Denise Crispim

    2014-01-01

    Bixin is a carotenoid found in the seeds of Bixa orellana L., a plant native to tropical America that is used in the food industry. The aim of this study was to investigate the effect of bixin on DNA damage and pre-neoplastic lesions induced by 1,2-dimethylhydrazine (DMH) in the liver and colon of Wistar rats. The animals received bixin at daily doses of 0.1, 1.0 and 10mg/kg body weight (bw) by gavage. For the assessment of DNA damage in hepatocytes and colon cells with the comet assay, the administration of bixin was for 7 days. The animals received a single subcutaneous injection of 25mg/kg bw of DMH, and were euthanized 4h later. For the evaluation of the frequency of aberrant crypt foci (ACF), the animals were treated with the different doses of bixin for 4 weeks. Four doses of 40mg/kg bw DMH, two doses in the first week and two doses in the second week, were administered and euthanasia occurred at 4 weeks after the beginning of treatment. Bixin reduced the frequency of DNA damage in hepatocytes at the highest two doses tested (1.0 and 10mg/kg bw). On the other hand, no differences in the frequency of DNA damage in colon cells were observed between animals treated with bixin plus DMH and those treated with DMH alone. In addition, the frequency of ACF did not differ significantly between the group treated with bixin plus DMH and the DMH group. The results suggest that bixin does not suppress the formation of ACF, indicating the absence of a protective effect against colon carcinogenesis. PMID:24246722

  16. Anti-genotoxic effect of Aloysia triphylla infusion against acrylamide-induced DNA damage as shown by the comet assay technique.

    Science.gov (United States)

    Zamorano-Ponce, E; Morales, C; Ramos, D; Sepúlveda, C; Cares, S; Rivera, P; Fernández, J; Carballo, M A

    2006-02-28

    Aloysia triphylla a perennial, bushy plant originally from South America has long been used in traditional medicine. Its aqueous extract contains considerable amounts of polyphenolic compounds, namely flavonoids and phenolic acids. In view of the interest in natural phenolic compounds as antioxidant in preventive medicine, this study was undertaken to investigate the chemoprotective effects of cedron leaves infusion against the genetic damage induced by acrylamide (AA) by using the alkaline version of the comet assay technique. Mice were separated in nine groups (eight animals each): (I) untreated, (II) negative control, (III) treated with infusion of cedron leaves 5%, 20 days twice a day, (IV) treated with AA (5 mg/kg b.w.), (V) treated with AA (20 mg/kg b.w.), (VI) treated with AA (30 mg/kg b.w.), (VII) treated with AA (50 mg/kg b.w.), (VIII) pretreated with infusion and treated with AA (50 mg/kg b.w.) and (IX) positive control (cyclophosphamide, 20 mg/kg b.w.). Three hundred blast cells were digitally evaluated per animal from three different slides (100 each). Media of tail moment (TM) values were analyzed by ANOVA test. No statistical differences (p>0.05) were found between untreated animals, negative control and infusion-treated mice. A single dose of AA-induced genetic damage as revealed by a statistically significant increase in TM values (p0.05) and exhibit statistical differences from animals treated only with AA (p<0.01). Cell viability was at least 90% in all cases as measured by the trypan blue exclusion method. The ferric reducing ability of plasma (FRAP) method reveals that the plasma of infusion-treated mice has a significantly higher antioxidant capacity than plasma from controls (p<0.01). The results suggest that the infusion could exerts an in vivo chemo protective action, probably due to its scavenging potency towards free radicals. PMID:16413820

  17. Anti-genotoxic effect of Aloysia triphylla infusion against acrylamide-induced DNA damage as shown by the comet assay technique.

    Science.gov (United States)

    Zamorano-Ponce, E; Morales, C; Ramos, D; Sepúlveda, C; Cares, S; Rivera, P; Fernández, J; Carballo, M A

    2006-02-28

    Aloysia triphylla a perennial, bushy plant originally from South America has long been used in traditional medicine. Its aqueous extract contains considerable amounts of polyphenolic compounds, namely flavonoids and phenolic acids. In view of the interest in natural phenolic compounds as antioxidant in preventive medicine, this study was undertaken to investigate the chemoprotective effects of cedron leaves infusion against the genetic damage induced by acrylamide (AA) by using the alkaline version of the comet assay technique. Mice were separated in nine groups (eight animals each): (I) untreated, (II) negative control, (III) treated with infusion of cedron leaves 5%, 20 days twice a day, (IV) treated with AA (5 mg/kg b.w.), (V) treated with AA (20 mg/kg b.w.), (VI) treated with AA (30 mg/kg b.w.), (VII) treated with AA (50 mg/kg b.w.), (VIII) pretreated with infusion and treated with AA (50 mg/kg b.w.) and (IX) positive control (cyclophosphamide, 20 mg/kg b.w.). Three hundred blast cells were digitally evaluated per animal from three different slides (100 each). Media of tail moment (TM) values were analyzed by ANOVA test. No statistical differences (p>0.05) were found between untreated animals, negative control and infusion-treated mice. A single dose of AA-induced genetic damage as revealed by a statistically significant increase in TM values (p0.05) and exhibit statistical differences from animals treated only with AA (p<0.01). Cell viability was at least 90% in all cases as measured by the trypan blue exclusion method. The ferric reducing ability of plasma (FRAP) method reveals that the plasma of infusion-treated mice has a significantly higher antioxidant capacity than plasma from controls (p<0.01). The results suggest that the infusion could exerts an in vivo chemo protective action, probably due to its scavenging potency towards free radicals.

  18. Genotoxicity of streptonigrin: a review.

    Science.gov (United States)

    Bolzán, A D; Bianchi, M S

    2001-03-01

    Streptonigrin (SN, CAS no. 3930-19-6) is an aminoquinone antitumor antibiotic isolated from cultures of Streptomyces flocculus. This compound is a member of a group of antitumor agents which possess the aminoquinone moiety and that includes also mitomycin C, porfiromycin, actinomycin, rifamycin and geldanamycin. Because of the potential use of SN in clinical chemotherapy, the study of its genotoxicity has considerable practical significance.SN inhibits the synthesis of DNA and RNA, causes DNA strand breaks after reduction with NADH, induces unscheduled DNA synthesis and DNA adducts and inhibits topoisomerase II. At the chromosome level, this antibiotic causes chromosome damage and increases the frequency of sister-chromatid exchanges.SN cleaves DNA in cell-free systems by a mechanism that involves complexing with metal ions and autoxidation of the quinone moiety to semiquinone in the presence of NADH with production of oxygen-derived reactive species. Recent evidence strongly suggests that the clastogenic action of this compound is partially mediated by free radicals. The present review aims at summarizing past and current knowledge concerning the genotoxic effects of SN. PMID:11223403

  19. "Aspartame: A review of genotoxicity data".

    Science.gov (United States)

    Kirkland, David; Gatehouse, David

    2015-10-01

    Aspartame is a methyl ester of a dipeptide of aspartic acid and phenylalanine. It is 200× sweeter than sucrose and is approved for use in food products in more than 90 countries around the world. Aspartame has been evaluated for genotoxic effects in microbial, cell culture and animal models, and has been subjected to a number of carcinogenicity studies. The in vitro and in vivo genotoxicity data available on aspartame are considered sufficient for a thorough evaluation. There is no evidence of induction of gene mutations in a series of bacterial mutation tests. There is some evidence of induction of chromosomal damage in vitro, but this may be an indirect consequence of cytotoxicity. The weight of evidence from in vivo bone marrow micronucleus, chromosomal aberration and Comet assays is that aspartame is not genotoxic in somatic cells in vivo. The results of germ cell assays are difficult to evaluate considering limited data available and deviations from standard protocols. The available data therefore support the conclusions of the European Food Safety Authority (EFSA) that aspartame is non-genotoxic.

  20. Genotoxic effect of alkaloids

    Directory of Open Access Journals (Sweden)

    J. A. P. Henriques

    1991-01-01

    Full Text Available Because of the increase use of alkaloids in general medical practice in recent years, it is of interest to determine genotoxic, mutagenic and recombinogenic response to different groups of alkaloids in prokaryotic and eucaryotic organisms. Reserpine, boldine and chelerythrine did not show genotoxicity response in the SOS-Chromotest whereas skimmianine showed genotixicity in the presence of a metabolic activation mixture. Voacristine isolated fromthe leaves of Ervatamia coronaria shows in vivo cytostatic and mutagenic effects in Saccharomyces cerevisiae hapioids cells. The Rauwolfia alkaloid (reserpine was not able to induce reverse mutation and recombinational mitotic events (crossing-over and gene conversion in yeast diploid strain XS2316.

  1. Benzene-induced genotoxicity in mice in vivo detected by the alkaline comet assay

    DEFF Research Database (Denmark)

    Tuo, J; Loft, S; Thomsen, M S;

    1996-01-01

    The myelotoxic and genotoxic effects of benzene have been related to oxidative DNA damage after metabolism by CYP2E1. Single cell gel electrophoresis (alkaline comet assay) detects DNA damage and may thus be a convenient method for the study of benzene genotoxicity. Benzene exposure to NMRI mice.......01). By comparing our data with those from genotoxicity studies on benzene using other methods, we conclude that the 'alkaline comet assay' is a sensitive method to detect DNA damage induced by benzene. We also infer that CYP2E1 contributes, at least partly, to the formation of the 'comet'-inducing metabolites...

  2. Evaluation of protective effect of amifostine on dacarbazine induced genotoxicity.

    Science.gov (United States)

    Etebari, M; Jafarian-Dehkordi, A; Lame, V

    2015-01-01

    Anticancer therapy with alkylating agents has been used for many years. Dacarbazine (DTIC) as an alkylating agent is used alone or in combination with other chemotherapy drugs. In order to inhibit the formation of secondary cancers resulting from chemotherapy with DTIC, preventional strategies is necessary. The present study was undertaken to evaluate the genoprotective effect of amifostine on the genotoxic effects of DTIC in cell culture condition. To determine the optimum genotoxic concentration of DTIC, HepG2 cells were incubated with various DTIC concentrations including 5, 10 and 20 μg/ml for 2 h and the genotoxic effects were evaluated by the comet assay. The result of this part of the study showed that incubation of HepG2 cells with DTIC at 5 μg/ml was sufficient to produce genotoxic effect. In order to determine the protective effects of amifostine on genotoxicity induced by DTIC, HepG2 cells were incubated with different concentrations of amifostine (2, 3 and 5 mg/ml) for 1 h which was followed by incubation with DTIC at 5 μg/ml for 2 h. One hour incubation of cells with different concentrations of amifostine before incubation with DITC indicated that at least 5 mg/ml concentration of amifostine can prevent genotoxic effects induced by DTIC on HepG2 cells under described condition. In conclusion amifostine could prevent DNA damage induced by DTIC on HepG2 cells. PMID:26430459

  3. Detection of genotoxic and non-genotoxic carcinogens in Xpc−/−p53+/− mice

    International Nuclear Information System (INIS)

    An accurate assessment of the carcinogenic potential of chemicals and pharmaceutical drugs is essential to protect humans and the environment. Therefore, substances are extensively tested before they are marketed to the public. Currently, the rodent two-year bioassay is still routinely used to assess the carcinogenic potential of substances. However, over time it has become clear that this assay yields false positive results and also has several economic and ethical drawbacks including the use of large numbers of animals, the long duration, and the high cost. The need for a suitable alternative assay is therefore high. Previously, we have proposed the Xpa*p53 mouse model as a very suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic carcinogen identification and can identify both genotoxic and non-genotoxic carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53 mice towards several genotoxic and non-genotoxic carcinogens. Furthermore, Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of DNA damaging agents and as such clearly respond in a similar way as wild type mice do. These advantageous traits of the Xpc*p53 model make it a better alternative for in vivo carcinogen testing than Xpa*p53. This pilot study suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both genotoxic and non-genotoxic carcinogens and as such represent a suitable alternative to possibly replace the murine life time cancer bioassay. Highlights: ► The Xpc*p53 mouse model is able to identify genotoxic and non-genotoxic carcinogens. ► Time, animals and cost can be significantly reduced compared to the 2-year bioassay. ► Xpc*p53 mice are more advantageous for carcinogen identification than Xpa*p53 mice. ► Xpc*p53 mice exhibit a wild type response upon exposure to genotoxicants.

  4. Signs of deferasirox genotoxicity

    OpenAIRE

    Ila, Hasan Basri; Topaktas, Mehmet; Arslan, Mehmet; BÜYÜKLEYLA, Mehmet

    2013-01-01

    Iron overload is a major health problem for patients who have to have continuous blood transfusions. It brings some metabolic problems together. Various iron chelating agents are being used for treatment of hemochromatosis which arises from excess iron accumulation. This study was conducted with the aim of determining whether deferasirox used as an iron chelator in patients with hemochromatosis has genotoxic effects. Commercial form of deferasirox, Exjade was used as test material. Test mater...

  5. 4-Aminoantipyrine reduces toxic and genotoxic effects of doxorubicin, cisplatin, and cyclophosphamide in male mice.

    Science.gov (United States)

    Berno, Claudia Rodrigues; Rós, Barbara de Toledo; da Silveira, Ingridhy Ostaciana Maia Freitas; Coelho, Henrique Rodrigues; Antoniolli, Andréia Conceição Milan Brochado; Beatriz, Adilson; de Lima, Dênis Pires; Monreal, Antônio Carlos Duenhas; Sousa, Fabricio Garmus; da Silva Gomes, Roberto; Oliveira, Rodrigo Juliano

    2016-07-01

    The analgesic drug dipyrone is used to treat side effects (including pain and fever) of cancer chemotherapeutic agents. Dipyrone is metabolized to 4-aminoantipyrine (4-AA), a PGE2-dependent blocker and inhibitor of cyclooxygenase (COX). We evaluated the genotoxic, mutagenic, apoptotic, and immunomodulatory activities of 4-AA in vivo and the effects of its combination with the antineoplastic drugs doxorubicin, cisplatin, and cyclophosphamide. 4-AA did not cause genotoxic/mutagenic damage, splenic phagocytosis, or leukocyte alterations. However, when combined with the antineoplastic agents, 4-AA decreased their genotoxic, mutagenic, apoptotic, and phagocytic effects. These results suggest that 4-AA might interfere with DNA damage-mediated chemotherapy. PMID:27402479

  6. "Stockpile" of Slight Transcriptomic Changes Determines the Indirect Genotoxicity of Low-Dose BPA in Thyroid Cells.

    Directory of Open Access Journals (Sweden)

    Immacolata Porreca

    Full Text Available Epidemiological and experimental data highlighted the thyroid-disrupting activity of bisphenol A (BPA. Although pivotal to identify the mechanisms of toxicity, direct low-dose BPA effects on thyrocytes have not been assessed. Here, we report the results of microarray experiments revealing that the transcriptome reacts dynamically to low-dose BPA exposure, adapting the changes in gene expression to the exposure duration. The response involves many genes, enriching specific pathways and biological functions mainly cell death/proliferation or DNA repair. Their expression is only slightly altered but, since they enrich specific pathways, this results in major effects as shown here for transcripts involved in the DNA repair pathway. Indeed, even though no phenotypic changes are induced by the treatment, we show that the exposure to BPA impairs the cell response to further stressors. We experimentally verify that prolonged exposure to low doses of BPA results in a delayed response to UV-C-induced DNA damage, due to impairment of p21-Tp53 axis, with the BPA-treated cells more prone to cell death and DNA damage accumulation. The present findings shed light on a possible mechanism by which BPA, not able to directly cause genetic damage at environmental dose, may exert an indirect genotoxic activity.

  7. “Stockpile” of Slight Transcriptomic Changes Determines the Indirect Genotoxicity of Low-Dose BPA in Thyroid Cells

    Science.gov (United States)

    Porreca, Immacolata; Ulloa Severino, Luisa; D’Angelo, Fulvio; Cuomo, Danila; Ceccarelli, Michele; Altucci, Lucia; Amendola, Elena; Nebbioso, Angela; Mallardo, Massimo

    2016-01-01

    Epidemiological and experimental data highlighted the thyroid-disrupting activity of bisphenol A (BPA). Although pivotal to identify the mechanisms of toxicity, direct low-dose BPA effects on thyrocytes have not been assessed. Here, we report the results of microarray experiments revealing that the transcriptome reacts dynamically to low-dose BPA exposure, adapting the changes in gene expression to the exposure duration. The response involves many genes, enriching specific pathways and biological functions mainly cell death/proliferation or DNA repair. Their expression is only slightly altered but, since they enrich specific pathways, this results in major effects as shown here for transcripts involved in the DNA repair pathway. Indeed, even though no phenotypic changes are induced by the treatment, we show that the exposure to BPA impairs the cell response to further stressors. We experimentally verify that prolonged exposure to low doses of BPA results in a delayed response to UV-C-induced DNA damage, due to impairment of p21-Tp53 axis, with the BPA-treated cells more prone to cell death and DNA damage accumulation. The present findings shed light on a possible mechanism by which BPA, not able to directly cause genetic damage at environmental dose, may exert an indirect genotoxic activity. PMID:26982218

  8. "Stockpile" of Slight Transcriptomic Changes Determines the Indirect Genotoxicity of Low-Dose BPA in Thyroid Cells.

    Science.gov (United States)

    Porreca, Immacolata; Ulloa Severino, Luisa; D'Angelo, Fulvio; Cuomo, Danila; Ceccarelli, Michele; Altucci, Lucia; Amendola, Elena; Nebbioso, Angela; Mallardo, Massimo; De Felice, Mario; Ambrosino, Concetta

    2016-01-01

    Epidemiological and experimental data highlighted the thyroid-disrupting activity of bisphenol A (BPA). Although pivotal to identify the mechanisms of toxicity, direct low-dose BPA effects on thyrocytes have not been assessed. Here, we report the results of microarray experiments revealing that the transcriptome reacts dynamically to low-dose BPA exposure, adapting the changes in gene expression to the exposure duration. The response involves many genes, enriching specific pathways and biological functions mainly cell death/proliferation or DNA repair. Their expression is only slightly altered but, since they enrich specific pathways, this results in major effects as shown here for transcripts involved in the DNA repair pathway. Indeed, even though no phenotypic changes are induced by the treatment, we show that the exposure to BPA impairs the cell response to further stressors. We experimentally verify that prolonged exposure to low doses of BPA results in a delayed response to UV-C-induced DNA damage, due to impairment of p21-Tp53 axis, with the BPA-treated cells more prone to cell death and DNA damage accumulation. The present findings shed light on a possible mechanism by which BPA, not able to directly cause genetic damage at environmental dose, may exert an indirect genotoxic activity. PMID:26982218

  9. In vivo genotoxicity of estragole in male F344 rats.

    Science.gov (United States)

    Ding, Wei; Levy, Dan D; Bishop, Michelle E; Pearce, Mason G; Davis, Kelly J; Jeffrey, Alan M; Duan, Jian-Dong; Williams, Gary M; White, Gene A; Lyn-Cook, Lascelles E; Manjanatha, Mugimane G

    2015-05-01

    Estragole, a naturally occurring constituent of various herbs and spices, is a rodent liver carcinogen which requires bio-activation. To further understand the mechanisms underlying its carcinogenicity, genotoxicity was assessed in F344 rats using the comet, micronucleus (MN), and DNA adduct assays together with histopathological analysis. Oxidative damage was measured using human 8-oxoguanine-DNA-N-glycosylase (hOGG1) and EndonucleaseIII (EndoIII)-modified comet assays. Results with estragole were compared with the structurally related genotoxic carcinogen, safrole. Groups of seven-week-old male F344 rats received corn oil or corn oil containing 300, 600, or 1,000 mg/kg bw estragole and 125, 250, or 450 mg/kg bw safrole by gavage at 0, 24, and 45 hr and terminated at 48 hr. Estragole-induced dose-dependent increases in DNA damage following EndoIII or hOGG1 digestion and without enzyme treatment in liver, the cancer target organ. No DNA damage was detected in stomach, the non-target tissue for cancer. No elevation of MN was observed in reticulocytes sampled from peripheral blood. Comet assays, both without digestion or with either EndoIII or hOGG1 digestion, also detected DNA damage in the liver of safrole-dosed rats. No DNA damage was detected in stomach, nor was MN elevated in peripheral blood following dosing with safrole suggesting that, as far both safrole and estragole, oxidative damage may contribute to genotoxicity. Taken together, these results implicate multiple mechanisms of estragole genotoxicity. DNA damage arises from chemical-specific interaction and is also mediated by oxidative species.

  10. p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Shi-Wei [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Wu, Chun-Ying [Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wang, Yen-Ting [Department of Medical Research and Education, Cheng Hsin General Hospital, Taipei, Taiwan (China); Kao, Jun-Kai [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Department of Pediatrics, Children' s Hospital, Changhua Christian Hospital, Changhua, Taiwan (China); Lin, Chi-Chen; Chang, Chia-Che; Mu, Szu-Wei; Chen, Yu-Yu [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Chiu, Husan-Wen [Institute of Biotechnology, National Cheng-Kung University, Tainan, Taiwan (China); Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan (China); Chang, Chuan-Hsun [Department of Surgical Oncology, Cheng Hsin General Hospital, Taipei, Taiwan (China); Department of Nutrition Therapy, Cheng Hsin General Hospital, Taipei, Taiwan (China); School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan (China); Liang, Shu-Mei [Institute of Biotechnology, National Cheng-Kung University, Tainan, Taiwan (China); Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan (China); Chen, Yi-Ju [Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Huang, Jau-Ling [Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan (China); Shieh, Jeng-Jer, E-mail: shiehjj@vghtc.gov.tw [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan (China)

    2013-02-15

    Compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), has been reported to cause apoptotic cell death in myeloma, breast cancer cells and glioma cells. In this study, we have demonstrated that compound C not only induced autophagy in all tested skin cancer cell lines but also caused more apoptosis in p53 wildtype skin cancer cells than in p53-mutant skin cancer cells. Compound C can induce upregulation, phosphorylation and nuclear translocalization of the p53 protein and upregulate expression of p53 target genes in wildtype p53-expressing skin basal cell carcinoma (BCC) cells. The changes of p53 status were dependent on DNA damage which was caused by compound C induced reactive oxygen species (ROS) generation and associated with activated ataxia-telangiectasia mutated (ATM) protein. Using the wildtype p53-expressing BCC cells versus stable p53-knockdown BCC sublines, we present evidence that p53-knockdown cancer cells were much less sensitive to compound C treatment with significant G2/M cell cycle arrest and attenuated the compound C-induced apoptosis but not autophagy. The compound C induced G2/M arrest in p53-knockdown BCC cells was associated with the sustained inactive Tyr15 phosphor-Cdc2 expression. Overall, our results established that compound C-induced apoptosis in skin cancer cells was dependent on the cell's p53 status. - Highlights: ► Compound C caused more apoptosis in p53 wildtype than p53-mutant skin cancer cells. ► Compound C can upregulate p53 expression and induce p53 activation. ► Compound C induced p53 effects were dependent on ROS induced DNA damage pathway. ► p53-knockdown attenuated compound C-induced apoptosis but not autophagy. ► Compound C-induced apoptosis in skin cancer cells was dependent on p53 status.

  11. p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells

    International Nuclear Information System (INIS)

    Compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), has been reported to cause apoptotic cell death in myeloma, breast cancer cells and glioma cells. In this study, we have demonstrated that compound C not only induced autophagy in all tested skin cancer cell lines but also caused more apoptosis in p53 wildtype skin cancer cells than in p53-mutant skin cancer cells. Compound C can induce upregulation, phosphorylation and nuclear translocalization of the p53 protein and upregulate expression of p53 target genes in wildtype p53-expressing skin basal cell carcinoma (BCC) cells. The changes of p53 status were dependent on DNA damage which was caused by compound C induced reactive oxygen species (ROS) generation and associated with activated ataxia-telangiectasia mutated (ATM) protein. Using the wildtype p53-expressing BCC cells versus stable p53-knockdown BCC sublines, we present evidence that p53-knockdown cancer cells were much less sensitive to compound C treatment with significant G2/M cell cycle arrest and attenuated the compound C-induced apoptosis but not autophagy. The compound C induced G2/M arrest in p53-knockdown BCC cells was associated with the sustained inactive Tyr15 phosphor-Cdc2 expression. Overall, our results established that compound C-induced apoptosis in skin cancer cells was dependent on the cell's p53 status. - Highlights: ► Compound C caused more apoptosis in p53 wildtype than p53-mutant skin cancer cells. ► Compound C can upregulate p53 expression and induce p53 activation. ► Compound C induced p53 effects were dependent on ROS induced DNA damage pathway. ► p53-knockdown attenuated compound C-induced apoptosis but not autophagy. ► Compound C-induced apoptosis in skin cancer cells was dependent on p53 status

  12. Evaluation of Cytotoxicity and Genotoxicity of Acacia aroma Leaf Extracts

    Directory of Open Access Journals (Sweden)

    C. M. Mattana

    2014-01-01

    Full Text Available Acacia aroma, native plant from San Luis, Argentina, is commonly used as antiseptic and for healing of wounds. The present study was conducted to investigate the in vitro cytotoxicity and genotoxicity of hot aqueous extract (HAE and ethanolic extract (EE of A. aroma. The cytotoxic activity was assayed by neutral red uptake assay on Vero cell. Cell treatment with a range from 100 to 5000 μg/mL of HAE and EE showed that 500 μg/mL and 100 μg/mL were the maximum noncytotoxic concentrations, respectively. The CC50 was 658 μg/mL for EE and 1020 μg/mL for HAE. The genotoxicity was tested by the single-cell gel electrophoresis comet assay. The results obtained in the evaluation of DNA cellular damage exposed to varied concentrations of the HAE showed no significant genotoxic effect at range of 1–20 mg/mL. The EE at 20 mg/mL showed moderate genotoxic effect related to the increase of the DNA percentage contained in tail of the comet; DNA was classified in category 2. At concentrations below 5 mg/mL, the results of cytotoxicity and genotoxicity of aqueous and ethanolic extracts of Acacia aroma guarantee the safety at cell and genomic level. However further studies are needed for longer periods including animal models to confirm the findings.

  13. Evaluation of genotoxicity of combined soil pollution by cadmium and imidacloprid

    Institute of Scientific and Technical Information of China (English)

    LIN; Aijun; ZHU; Yongguan; TONG; Yiping

    2005-01-01

    Cadmium (Cd) is one of the important pollutants of soil and the genotoxicity of Cd-contaminated soil was studied in combination with imidacloprid. The single cell gel electrophoresis or comet assay was used to quantify DNA strand breaks as a measure of DNA damage induced by Cd and imidacloprid contamination in soil. The soil was artificially contaminated by Cd 2 h at 25℃ and were used in the comet assay. DNA damage was measured as the values of percentage of nuclei with tails, tail length, tail DNA, tail moment (TM), and Olive tail moment (OTM). DNA damages of root tips of Vicia faba increased after Cd treatment and there were dose-related increases in DNA damage measured as these parameters. However, the addition of imidacloprid further increased the DNA damage. These data confirmed the genotoxic effect of Cd to plants, and that the combined pollution with imidacloprid can enhance the genotoxicity of Cd.

  14. Genotoxicity Studies Performed in the Ecuadorian Population

    Directory of Open Access Journals (Sweden)

    César Paz-y-Miño

    2012-01-01

    Full Text Available Genotoxicity studies in Ecuador have been carried out during the past two decades. The focuses of the research were mainly the area of environmental issues, where the populations have been accidentally exposed to contaminants and the area of occupational exposure of individuals at the workplace. This paper includes studies carried out in the population of the Amazon region, a zone known for its rich biodiversity as well as for the ecological damage caused by oil spills and chemical sprayings whose consequences continue to be controversial. Additionally, we show the results of studies comprised of individuals occupationally exposed to toxic agents in two very different settings: flower plantation workers exposed to pesticide mixtures and X-ray exposure of hospital workers. The results from these studies confirm that genotoxicity studies can help evaluate current conditions and prevent further damage in the populations exposed to contaminants. As such, they are evidence of the need for biomonitoring employers at risk, stricter law enforcement regarding the use of pesticides, and increasingly conscientious oil extraction activities.

  15. Genotoxicity studies performed in the ecuadorian population.

    Science.gov (United States)

    Paz-Y-Miño, César; Cumbal, Nadia; Sánchez, María Eugenia

    2012-01-01

    Genotoxicity studies in Ecuador have been carried out during the past two decades. The focuses of the research were mainly the area of environmental issues, where the populations have been accidentally exposed to contaminants and the area of occupational exposure of individuals at the workplace. This paper includes studies carried out in the population of the Amazon region, a zone known for its rich biodiversity as well as for the ecological damage caused by oil spills and chemical sprayings whose consequences continue to be controversial. Additionally, we show the results of studies comprised of individuals occupationally exposed to toxic agents in two very different settings: flower plantation workers exposed to pesticide mixtures and X-ray exposure of hospital workers. The results from these studies confirm that genotoxicity studies can help evaluate current conditions and prevent further damage in the populations exposed to contaminants. As such, they are evidence of the need for biomonitoring employers at risk, stricter law enforcement regarding the use of pesticides, and increasingly conscientious oil extraction activities.

  16. Methodological considerations for using umu assay to assess photo-genotoxicity of engineered nanoparticles

    DEFF Research Database (Denmark)

    Cupi, Denisa; Baun, Anders

    2016-01-01

    In this study we investigated the feasibility of high-throughput (96-well plate) umu assay to test the genotoxic effect of TiO2 engineered nanoparticles (ENPs) under UV light (full spectrum) and visible light (455nm). Exposure of TiO2 ENPs to up to 60min of UV light induced a photocatalytic...... production of ROS. However, UV light itself caused cytotoxic damage to Salmonella typhimurium at exposures >15min and a genotoxic effect at exposures >0.5min; and use of UV filters did not lower this effect. No genotoxicity of TiO2 ENPs was observed under visible light conditions at concentrations up to 100...

  17. Genotoxic potential of nonsteroidal hormones

    Directory of Open Access Journals (Sweden)

    Topalović Dijana

    2015-01-01

    Full Text Available Hormones are cellular products involved in the regulation of a large number of processes in living systems, and which by their actions affect the growth, function and metabolism of cells. Considering that hormones are compounds normally present in the organism, it is important to determine if they can, under certain circumstances, lead to genetic changes in the hereditary material. Numerous experimental studies in vitro and in vivo in different systems, from bacteria to mammals, dealt with the mutagenic and genotoxic effects of hormones. This work presents an overview of the research on genotoxic effects of non­steroidal hormones, although possible changes of genetic material under their influence have not still been known enough, and moreover, investigations on their genotoxic influence have given conflicting results. The study results show that mechanisms of genotoxic effect of nonsteroidal hormones are manifested through the increase of oxidative stress by arising reactive oxygen species. A common mechanism of ROS occurence in thyroid hormones and catecholamines is through metabolic oxidation of their phenolic groups. Manifestation of insulin genotoxic effect is based on production of ROS by activation of NADPH isophorms, while testing oxytocin showed absence of genotoxic effect. Considering that the investigations on genotoxicity of nonsteroidal hormones demonstrated both positive and negative results, the explanation of this discordance involve limitations of test systems themselves, different cell types or biological species used in the experiments, different level of reactivity in vitro and in vivo, as well as possible variations in a tissue-specific expression. Integrated, the provided data contribute to better understanding of genotoxic effect of nonsteroidal hormones and point out to the role and mode of action of these hormones in the process of occurring of effects caused by oxidative stress. [Projekat Ministarstva nauke Republike

  18. Cells behaviors and genotoxicity on topological surface

    Energy Technology Data Exchange (ETDEWEB)

    Yang, N.; Yang, M.K.; Bi, S.X. [Tianjin Key Laboratory of Fiber Modification and Functional Fiber, School of Materials Science and Engineering, Tianjin Polytechnic University, Tianjin, 300387 (China); Chen, L., E-mail: chenlis@tjpu.edu.cn [Tianjin Key Laboratory of Fiber Modification and Functional Fiber, School of Materials Science and Engineering, Tianjin Polytechnic University, Tianjin, 300387 (China); Zhu, Z.Y.; Gao, Y.T.; Du, Z. [Tianjin Key Laboratory of Artificial Cell, Tianjin Third Central Hospital, Tianjin, 300170 (China)

    2013-08-01

    To investigate different cells behaviors and genotoxicity, which were driven by specific microenvironments, three patterned surfaces (pillars, wide grooves and narrow grooves) and one smooth surface were prepared by template-based technique. Vinculin is a membrane-cytoskeletal protein in focal adhesion plaques and associates with cell–cell and cell–matrix junctions, which can promote cell adhesion and spreading. The immunofluorescence staining of vinculin revealed that the narrow grooves patterned substrate was favorable for L929 cell adhesion. For cell multiplication, the narrow grooves surface was fitted for the proliferation of L929, L02 and MSC cells, the pillars surface was only in favor of L929 cells to proliferate during 7 days of cell cultivation. Cell genetic toxicity was evaluated by cellular micronuclei test (MNT). The results indicated that topological surfaces were more suitable for L929 cells to proliferate and maintain the stability of genome. On the contrary, the narrow grooves surface induced higher micronuclei ratio of L02 and MSC cells than other surfaces. With the comprehensive results of cell multiplication and MNT, it was concluded that the wide grooves surface was best fitted for L02 cells to proliferate and have less DNA damages, and the smooth surface was optimum for the research of MSC cells in vitro. - Highlights: • Different cells behaviors on microstructure surfaces were discussed in this paper. • The expression of cell protein of Vinculin was studied in this research. • Cellular micronuclei test was applied to evaluate cells' genotoxicity. • Cell genotoxicity was first studied in the research field of topological surfaces.

  19. Evaluation of perfluorooctanoate for potential genotoxicity

    Directory of Open Access Journals (Sweden)

    John L. Butenhoff

    2014-01-01

    Full Text Available Perfluorooctanoate (PFOA is a fully fluorinated eight-carbon fatty acid analog with exceptional stability toward degradation that has been used as an industrial surfactant and has been detected in environmental and biological matrices. Exposures to PFOA in the workplace and in the environment have continuously stimulated investigations into its potential human health hazards. In this article, the results of fifteen unpublished genotoxicity assays conducted with perfluorooctanoate (as either the linear or linear/branched ammonium salt (APFO or the linear/branched sodium salt are reported and include: seven mutation assays (three in vitro reverse mutation assays with histidine auxotrophic strains of Salmonella typhimurium, two in vitro reverse mutation assays with the tryptophan auxotrophic Escherichia coli WP2uvr strain, one in vitro mitotic recombination (gene conversion assay with Saccharomyces cerevisiae D4, and an in vitro Chinese hamster ovary (CHO HGPRT forward mutation assay; seven studies to assess potential for chromosomal damage (three in vitro CHO chromosomal aberration studies, an in vitro human whole blood lymphocyte chromosomal aberration study, and three in vivo mouse micronucleus assays; and an in vitro C3H 10T1/2 cell transformation assay. Although PFOA has not been demonstrated to be metabolized, all in vitro assays were conducted both in the presence and in the absence of a mammalian hepatic microsomal activation system. These assays were originally described in twelve contract laboratory reports which have been available via the United States Environmental Protection Agency public docket (Administrative Record 226 for over a decade; however, the details of these assays have not been published previously in the open scientific literature. With the exception of limited positive findings at high and cytotoxic concentrations in some assay trials which reflected the likely consequence of cytotoxic disruption of normal cellular

  20. Evaluation of Genotoxic Pressure along the Sava River.

    Science.gov (United States)

    Kolarević, Stoimir; Aborgiba, Mustafa; Kračun-Kolarević, Margareta; Kostić, Jovana; Simonović, Predrag; Simić, Vladica; Milošković, Aleksandra; Reischer, Georg; Farnleitner, Andreas; Gačić, Zoran; Milačič, Radmila; Zuliani, Tea; Vidmar, Janja; Pergal, Marija; Piria, Marina; Paunović, Momir; Vuković-Gačić, Branka

    2016-01-01

    In this study we have performed a comprehensive genotoxicological survey along the 900 rkm of the Sava River. In total, 12 sites were chosen in compliance with the goals of GLOBAQUA project dealing with the effects of multiple stressors on biodiversity and functioning of aquatic ecosystems. The genotoxic potential was assessed using a complex battery of bioassays performed in prokaryotes and aquatic eukaryotes (freshwater fish). Battery comprised evaluation of mutagenicity by SOS/umuC test in Salmonella typhimurium TA1535/pSK1002. The level of DNA damage as a biomarker of exposure (comet assay) and biomarker of effect (micronucleus assay) and the level of oxidative stress as well (Fpg-modified comet assay) was studied in blood cells of bleak and spirlin (Alburnus alburnus/Alburnoides bipunctatus respectively). Result indicated differential sensitivity of applied bioassays in detection of genotoxic pressure. The standard and Fpg-modified comet assay showed higher potential in differentiation of the sites based on genotoxic potential in comparison with micronucleus assay and SOS/umuC test. Our data represent snapshot of the current status of the river which indicates the presence of genotoxic potential along the river which can be traced to the deterioration of quality of the Sava River by communal and industrial wastewaters. The major highlight of the study is that we have provided complex set of data obtained from a single source (homogeneity of analyses for all samples). PMID:27631093

  1. Evaluation of Genotoxic Pressure along the Sava River

    Science.gov (United States)

    Kračun-Kolarević, Margareta; Kostić, Jovana; Simonović, Predrag; Simić, Vladica; Milošković, Aleksandra; Reischer, Georg; Farnleitner, Andreas; Gačić, Zoran; Milačič, Radmila; Zuliani, Tea; Vidmar, Janja; Pergal, Marija; Piria, Marina; Paunović, Momir; Vuković-Gačić, Branka

    2016-01-01

    In this study we have performed a comprehensive genotoxicological survey along the 900 rkm of the Sava River. In total, 12 sites were chosen in compliance with the goals of GLOBAQUA project dealing with the effects of multiple stressors on biodiversity and functioning of aquatic ecosystems. The genotoxic potential was assessed using a complex battery of bioassays performed in prokaryotes and aquatic eukaryotes (freshwater fish). Battery comprised evaluation of mutagenicity by SOS/umuC test in Salmonella typhimurium TA1535/pSK1002. The level of DNA damage as a biomarker of exposure (comet assay) and biomarker of effect (micronucleus assay) and the level of oxidative stress as well (Fpg—modified comet assay) was studied in blood cells of bleak and spirlin (Alburnus alburnus/Alburnoides bipunctatus respectively). Result indicated differential sensitivity of applied bioassays in detection of genotoxic pressure. The standard and Fpg—modified comet assay showed higher potential in differentiation of the sites based on genotoxic potential in comparison with micronucleus assay and SOS/umuC test. Our data represent snapshot of the current status of the river which indicates the presence of genotoxic potential along the river which can be traced to the deterioration of quality of the Sava River by communal and industrial wastewaters. The major highlight of the study is that we have provided complex set of data obtained from a single source (homogeneity of analyses for all samples). PMID:27631093

  2. Mutagenicity and genotoxicity of coal fly ash water leachate

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, R.; Mukherjee, A. [University of Calcutta, Calcutta (India). Dept. of Botany

    2009-03-15

    Fly ash is a by-product of coal-fired electricity generation plants. The prevalent practice of disposal is as slurry of ash and water to storage or ash ponds located near power stations. This has lain to waste thousands of hectares of land all over the world. Since leaching is often the cause of off-site contamination and pathway of introduction into the human environment, a study on the genotoxic effects of fly ash leachate is essential. Leachate prepared from the fly ash sample was analyzed for metal content, and tested for mutagenicity and genotoxicity. Analyses of metals show predominance of the metals - sodium, silicon, potassium, calcium, magnesium, iron, manganese, zinc, and sulphate. The Ames Salmonella mutagenicity assay, a short-term bacterial reverse mutation assay, was conducted on two-tester strains of Salmonella typhimurium strains TA97a and TA102. For genotoxicity, the alkaline version of comet assay on fly ash leachate was carried in vitro on human blood cells and in vivo on Nicotiana plants. The leachate was directly mutagenic and induced significantconcentration-dependent increases in DNA damage in whole blood cells, lymphocytes, and in Nicotiana plants. The comet parameters show increases in tail DNA percentage (%), tail length (mu m), and olive tail moment (arbitrary units). Our results indicate that leachate from fly ash dumpsites has the genotoxic potential and may lead to adverse effects on vegetation and on the health of exposed human populations.

  3. Detection of genotoxic and non-genotoxic carcinogens in Xpc{sup −/−}p53{sup +/−} mice

    Energy Technology Data Exchange (ETDEWEB)

    Melis, Joost P.M. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Leiden University Medical Center, Department of Toxicogenetics, Leiden (Netherlands); Speksnijder, Ewoud N. [Leiden University Medical Center, Department of Toxicogenetics, Leiden (Netherlands); Kuiper, Raoul V. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Dutch Molecular Pathology Center, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht (Netherlands); Salvatori, Daniela C.F. [Leiden University Medical Center, Central Animal Facility, Leiden (Netherlands); Schaap, Mirjam M. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Leiden University Medical Center, Department of Toxicogenetics, Leiden (Netherlands); Maas, Saskia [Leiden University Medical Center, Central Animal Facility, Leiden (Netherlands); Robinson, Joke; Verhoef, Aart; Benthem, Jan van; Luijten, Mirjam [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Steeg, Harry van, E-mail: Harry.van.Steeg@rivm.nl [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Leiden University Medical Center, Department of Toxicogenetics, Leiden (Netherlands)

    2013-01-15

    An accurate assessment of the carcinogenic potential of chemicals and pharmaceutical drugs is essential to protect humans and the environment. Therefore, substances are extensively tested before they are marketed to the public. Currently, the rodent two-year bioassay is still routinely used to assess the carcinogenic potential of substances. However, over time it has become clear that this assay yields false positive results and also has several economic and ethical drawbacks including the use of large numbers of animals, the long duration, and the high cost. The need for a suitable alternative assay is therefore high. Previously, we have proposed the Xpa*p53 mouse model as a very suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic carcinogen identification and can identify both genotoxic and non-genotoxic carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53 mice towards several genotoxic and non-genotoxic carcinogens. Furthermore, Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of DNA damaging agents and as such clearly respond in a similar way as wild type mice do. These advantageous traits of the Xpc*p53 model make it a better alternative for in vivo carcinogen testing than Xpa*p53. This pilot study suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both genotoxic and non-genotoxic carcinogens and as such represent a suitable alternative to possibly replace the murine life time cancer bioassay. Highlights: ► The Xpc*p53 mouse model is able to identify genotoxic and non-genotoxic carcinogens. ► Time, animals and cost can be significantly reduced compared to the 2-year bioassay. ► Xpc*p53 mice are more advantageous for carcinogen identification than Xpa*p53 mice. ► Xpc*p53 mice exhibit a wild type response upon exposure to genotoxicants.

  4. INVESTIGATION ON THE ANTI-GENOTOXIC EFFECT OF OCIMUM SANCTUM IN FLUORIDE INDUCED GENOTOXICITY

    Directory of Open Access Journals (Sweden)

    Kambam Srilatha

    2013-06-01

    Full Text Available The present study was designed to investigate the anti-genotoxic effect of Ocimum sanctum on fluoride induced genotoxicity and its impact on oxidative stress. Exposure to fluoride can mainly occur through drinking water when the levels far exceed the permissible limit. Fluorosis is a serious problem the world over resulting in damage to DNA. Micronuclei assessment from bone marrow and peripheral blood was used in the present study to assess the damage to DNA. Sodium fluoride in a single dose (30 mg/kg, i.p. was used to induce micronuclei in albino mice. Treatment with the aqueous extract of Ocimum sanctum was initiated in the single dose study (100, 400 & 800 mg/kg and as a time course for 1 day, 3 days and 7 days (100 mg/kg. 24 h after injecting sodium fluoride, the animals were sacrificed and micronuclei were determined from smears prepared from bone marrow and peripheral blood. The antioxidant impact of the extract was determined using ferric ion reducing capacity of plasma and thiobarbituric acid reactive substances as a measure of lipid peroxidation. All doses were capable of preventing the formation of micronuclei but 100 mg/kg of the aqueous extract was most efficacious as a single dose and in the time course study. The beneficial effect of Ocimum sanctum is possibly due to the synergistic action of constituents like polyphenols, triterpenoids, and flavonoids.

  5. Interaction between some common genotoxic agents.

    Science.gov (United States)

    Beckman, L; Nordenson, I

    1986-01-01

    The clastogenic effects of arsenic, lead and sulphur dioxide and the protective effect of selenium were studied in short-term lymphocyte cultures. The three agents selected are the major toxic substances in emissions from copper smelters. Cells from non-smoking, healthy individuals were exposed to individual agents and combinations of the four agents (sodium arsenite, lead acetate, sodium sulphite and sodium selenite) and the cells were analysed for chromosome aberrations and sister chromatide exchanges. Selenium showed an antagonistic (protective) effect against the other agents. No synergistic effects were found, and the interactions between arsenic, lead and sulphur dioxide were mainly antagonistic. These rather unexpected findings indicate that mixed exposure from copper smelters, and other mixed exposures where arsenic, lead and sulphur dioxide are involved, may cause less genetic damage than expected and that an adequate dietary supplement of selenium may reduce the genotoxic effects of these agents. PMID:3793119

  6. Cytotoxicity and genotoxicity assessment of Euphorbia hirta in MCF-7 cell line model using comet assay

    Institute of Scientific and Technical Information of China (English)

    Kwan Yuet Ping; Ibrahim Darah; Yeng Chen; Sreenivasan Sasidharan

    2013-01-01

    Objective:To evaluate the cytotoxicity and genotoxicity activity of Euphorbia hirta (E. hirta) in MCF-7 cell line model using comet assay. Methods: The cytotoxicity of E. hirta extract was investigated by employing brine shrimp lethality assay and the genotoxicity of E. hirta was assessed by using Comet assay. Results: Both toxicity tests exhibited significant toxicity result. In the comet assay, the E. hirta extract exhibited genotoxicity effects against MCF-7 DNA in a time-dependent manner by increasing mean percentage of DNA damage. The extract of E. hirta showed significant toxicity against brine shrimp with an LC50 value of 620.382 μg/mL (24 h). Comparison with positive control potassium dichromate signifies that cytotoxicity exhibited by the methanol extract might have moderate activity. Conclusion:The present work confirmed the cytotoxicity and genotoxicity of E. hirta. However, the observed toxicity of E. hirta extracts needs to be confirmed in additional studies.

  7. Anti-Genotoxic Potential of Bilirubin In Vivo

    DEFF Research Database (Denmark)

    Wallner, Marlies; Antl, Nadja; Rittmannsberger, Barbara;

    2013-01-01

    The bile pigment bilirubin is a known antioxidant and is associated with protection from cancer and cardiovascular disease (CVD) when present in too strong concentrations. Unconjugated bilirubin (UCB) might also possess anti-genotoxic potential by preventing oxidative damage to DNA. Moderately...... elevated bilirubin levels are found in individuals with Gilbert syndrome and more severe in the hyperbilirubinemic Gunn rat model. This study was therefore aimed to assess the levels of oxidative damage to DNA in Gilbert syndrome subjects and Gunn rats compared to matched controls. Seventy-six individuals...

  8. Glycidamide genotoxicity modulated by Caspases genes polymorphisms.

    Science.gov (United States)

    de Lima, João Pereira; Silva, Susana N; Rueff, José; Pingarilho, Marta

    2016-08-01

    Acrylamide (AA) is amongst acknowledged carcinogenic dietary factors. Its DNA-reactive metabolite is glycidamide (GA). The present study intended to correlate the role of key polymorphic genes of apoptosis (CASP7, CASP8, CASP9, CASP10, LTA and TNFRSF1B) with biomarkers of effect of DNA damage, namely the sister chromatid exchange assay (SCE) and the comet assay in whole blood cells exposed to GA. The aim was to assess as a proof of concept the role that pro-apoptotic effector proteins might have in the yields of genotoxic effects when those effector proteins are coded by polymorphic genes. Whole blood from a small group of volunteers was exposed to GA to assess DNA damage and the volunteers were genotyped for polymorphic genes related to apoptosis pathways. A relation between the induction of SCE and several variants of the polymorphism CASP8 rs1035142 G>T was observed. Also, a relation between the % tail DNA and the CASP10 I522L polymorphism was found. Furthermore, associations between % tail DNA and several SNP-SNP interactions of CASP8 and CASP10 were found. A possible correlation between DNA damage and the genetic susceptibility, bestowed by polymorphic genes in the apoptosis inducing pathways was verified. PMID:27062911

  9. Alkaline comet assay for genotoxic effect detection in neotropical fish Prochilodus lineatus (Pisces, Curimatidae).

    Science.gov (United States)

    Simoniello, M F; Gigena, F; Poletta, G; Loteste, A; Kleinsorge, E; Campana, M; Scagnetti, J; Parma, M J

    2009-08-01

    Toxicants on fish may induce genetic alterations that can be used as genotoxic markers. We evaluated DNA damage using alkaline comet assay applied on erythrocytes after in vivo exposure of Prochilodus lineatus to different concentrations of Cypermethrin (0.300, 0.150, 0.075 and 0.000 microg/L) as a probable chemical mutagen. The results revealed a significantly higher level of DNA damage at all concentrations of Cypermethrin tested compared to control and background level (p < 0.05). We have standardized the technique for one of the most common native fish species that will be useful for biomonitoring genotoxicity in polluted waters of the region. PMID:19466374

  10. Comet Assay: A Method to Evaluate Genotoxicity of Nano-Drug Delivery System

    OpenAIRE

    Morteza Eskandani; Somayeh Vandghanooni

    2011-01-01

    Introduction: Drug delivery systems could induce cellular toxicity as side effect of nanomaterials. The mechanism of toxicity usually involves DNA damage. The comet assay or single cell gel electrophoresis (SCGE) is a sensitive method for detecting strand damages in the DNA of a cell with applications in genotoxicity testing and molecular epidemiology as well as fundamental research in DNA damage and repair. Methods: In the current study, we reviewed recent drug delivery researches related to...

  11. Assessment of Genotoxicity of Ionizing radiation using Tradescantia-Comet assay

    International Nuclear Information System (INIS)

    Over the last two decades, several new methodologies for the detection of DNA damage have been developed. The comet assay is currently used in different areas of biological sciences to detect DNA damage. The comet assay, also called the single cell gel electrophoresis (SCGE) was first introduced by Ostling and Johanson as a microelectrophoretic technique for the direct visualization of DNA damage in individual cells. The comet assay, due to its simplicity, sensitivity and need of a few cells, is ideal as a short-term genotoxicity test. The comet assay can theoretically be applied to every type of eukaryotic cell, including plant cells. Plants are very useful as monitors of genetic effects caused by pollution in the atmosphere, water and soil. Although the genotoxic effects detected by Tradescantia tests cannot be associated with mutagenesis or even carcinogenesis in humans, these bioassays are very useful tools for screening the mutagenic potential in the environment. Experiments were conducted to study the genotoxic effects of ionizing radiations on the genome integrity, particularly of Tradescantia. The increasingly frequent use of Tradescantia as a sensitive environmental bioindicator of genotoxic effects. This study was designed to assess the genotoxicity of ionizing radiation using Tradescnatia-comet assay

  12. Recent Perspectives on the Relations between Fecal Mutagenicity, Genotoxicity, and Diet.

    Science.gov (United States)

    Gratz, Silvia W; Wallace, R John; El-Nezami, Hani S

    2011-01-01

    DNA damage is an essential component of the genesis of colonic cancer. Gut microbial products and food components are thought to be principally responsible for the damage that initiates disease progression. Modified Ames tests and Comet assays have been developed for measuring mutagenicity and genotoxicity. Their relevance to oncogenesis remains to be confirmed, as does the relative importance of different mutagenic and genotoxic compounds present in fecal water and the bacteria involved in their metabolism. Dietary intervention studies provide clues to the likely risks of oncogenesis. High-protein diets lead to increases in N-nitroso compounds in fecal water and greater DNA damage as measured by the Comet assay, for example. Other dietary interventions, such as non-digestible carbohydrates and probiotics, may lead to lower fecal genotoxicity. In order to make recommendations to the general public, we must develop a better understanding of how genotoxic compounds are formed in the colon, how accurate the Ames and Comet assays are, and how diet affects genotoxicity. PMID:21779247

  13. Recent perspectives on the relations between faecal mutagenicity, genotoxicity and diet

    Directory of Open Access Journals (Sweden)

    Silvia eGratz

    2011-03-01

    Full Text Available DNA damage is an essential component of the genesis of colonic cancer. Gut microbial products and food components are thought to be principally responsible for the damage that initiates disease progression. Modified Ames tests and Comet assays have been developed for measuring mutagenicity and genotoxicity. Their relevance to oncogenesis remains to be confirmed, as does the relative importance of different mutagenic and genotoxic compounds present in faecal water and the bacteria involved in their metabolism. Dietary intervention studies provide clues to the likely risks of oncogenesis. High-protein diets lead to increases in N-nitroso compounds in faecal water and greater DNA damage as measured by the Comet assay, for example. Other dietary interventions, such as non-digestible carbohydrates and probiotics, may lead to lower faecal genotoxicity. In order to make recommendations to the general public, we must develop a better understanding of how genotoxic compounds are formed in the colon, how accurate the Ames and Comet assays are, and how diet affects genotoxicity.

  14. Current investigations into the genotoxicity of zinc oxide and silica nanoparticles in mammalian models in vitro and in vivo: carcinogenic/genotoxic potential, relevant mechanisms and biomarkers, artifacts, and limitations

    Directory of Open Access Journals (Sweden)

    Kwon JY

    2014-12-01

    Full Text Available Jee Young Kwon,1,* Preeyaporn Koedrith,2,* Young Rok Seo1 1Department of Life Science, Institute of Environmental Medicine, Dongguk University, Seoul, Republic of Korea; 2Faculty of Environment and Resource Studies, Mahidol University, Phuttamonthon District, NakhonPathom, Thailand *These authors contributed equally to this work and should be considered as co-first authors Abstract: Engineered nanoparticles (NPs are widely used in many sectors, such as food, medicine, military, and sport, but their unique characteristics may cause deleterious health effects. Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated. In this review, we address some metal and metal oxide NPs of interest and current genotoxicity tests in vitro and in vivo. Metal NPs can cause DNA damage such as chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. We also discuss several parameters that may affect genotoxic response, including physicochemical properties, widely used assays/end point tests, and experimental conditions. Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors. Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed. Keywords: carcinogenicity, exposure assessment, genotoxicity, nanoparticles, risk evaluation

  15. Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress

    Science.gov (United States)

    Bassi, C; Ho, J; Srikumar, T; Dowling, RJO; Gorrini, C; Miller, SJ; Mak, TW; Neel, BG; Raught, B; Stambolic, V

    2016-01-01

    Loss of function of the Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor gene is associated with many human cancers. In the cytoplasm, PTEN antagonizes the Phosphatidylinositol 3′ kinase (PI3K) signaling pathway. PTEN also accumulates in the nucleus, where its function remains poorly understood. We demonstrate that SUMOylation (SUMO) of PTEN controls its nuclear localization. In cells exposed to genotoxic stress, SUMO-PTEN was rapidly excluded from the nucleus dependent on the protein kinase Ataxia telangiectasia mutated (ATM). Cells lacking nuclear PTEN were hypersensitive to DNA damage, while PTEN-deficient cells were susceptible to killing by a combination of genotoxic stress and a small molecule PI3K inhibitor both in vitro and in vivo. Our findings may have implications for individualized therapy for patients with PTEN-deficient tumors. PMID:23888040

  16. Genotoxicity of indium tin oxide by comet test

    Directory of Open Access Journals (Sweden)

    İbrahim Hakkı Ciğerci

    2015-06-01

    Full Text Available Indium tin oxide (ITO is used for liquid crystal display (LCDs, electrochromic displays, flat panel displays, field emission displays, touch or laptop computer screens, cell phones, energy conserving architectural windows, defogging aircraft and automobile windows, heat-reflecting coatings to increase light bulb efficiency, gas sensors, antistatic window coatings, wear resistant layers on glass, nanowires and nanorods because of its unique properties of high electrical conductivity, transparency and mechanical resistance.Genotoxic effects of ITO were investigated on the root cells of Allium cepa by Comet assay. A. cepa roots were treated with the aqueous dispersions of ITO at 5 different concentrations (12.5, 25, 50, 75, and 100 ppm for 4 h. A significant increase in DNA damage was a observed at all concentrations of ITO by Comet assay. These result indicate that ITO exhibit genotoxic activity in A. cepa root meristematic cells.

  17. El té verde en la quimioprevención in vivo del daño genotóxico inducido por metales cancerígenos (cromo [VI] Green tea and its role on chemoprevention in vivo of genotoxic damage induced by carcinogenic metals (Chromium [VI

    Directory of Open Access Journals (Sweden)

    M. C. García-Rodríguez

    2012-08-01

    las 72 horas, del 20 y 35% a las 48 horas y del 18 y 31% a las 24 horas con los tratamientos intragástricos y ad libitum respectivamente, en comparación con el grupo tratado solo con el trióxido de cromo. Por lo que, el té verde redujo el daño genotóxico inducido por el trióxido de cromo, y la mayor protección se presentó a las 72 horas. Conclusiones: Nuestros hallazgos muestran un efecto protector del té verde contra el daño al material genético inducido por compuestos metálicos como los del Cr [VI], sugiriendo que sus componentes antioxidantes son los que tienen un efecto quimiopreventivo sobre el EOx generado por el Cr [VI] durante su reducción a Cr [III]. El hecho de que la mayor disminución de la frecuencia de MN se observe a las 72 horas y con el tratamiento ad libitum, sugiere que el efecto protector depende de la biodisponibilidad, farmacodinámica y farmacocinética del principio activo del té verde, por lo que la administración del té verde durante tiempos más prolongados antes de la exposición con compuestos de Cr [VI] podría tener un efecto preventivo más consistente.Background: Consumption of green tea, by its antioxidant properties, has been associated with beneficial health effects, because antioxidant may play a role in the risk and pathogenesis of several chronic diseases, especially cardiovascular disease and cancer. On the other hand, it has been reported that metal compounds such as chromium [VI] are carcinogenic and can induce genotoxic damage through the Oxidative Stress. Therefore, it is possible that green tea has a protective effect against the genotoxic damage induced by this compounds. Objective: To evaluate the effect of oral administration of green tea over the genotoxic damage induced by Cr [VI] by quantification of micronucleus (MN in polychromatic erythrocytes (EPC. Materials and methods: We use mice of CD-1 strain that were randomly divided into the following groups: (i control, (ii treatment with green tea, (iii

  18. The Cytotoxicity and Genotoxicity of Hexavalent Chromium in Steller Sea Lion Lung Fibroblasts Compared to Human Lung Fibroblasts

    OpenAIRE

    Wise, John Pierce; Wise, Sandra S.; Holmes, Amie L.; LaCerte, Carolyne; Shaffiey, Fariba; Aboueissa, AbouEl-Makarim

    2010-01-01

    In this study we directly compared soluble and particulate chromate cytotoxicity and genotoxicity in human (Homo sapiens) and sea lion (Eumetopias jubatus) lung fibroblasts. Our results show that hexavalent chromium induces increased cell death and chromosome damage in both human and sea lion cells with increasing intracellular chromium ion levels. The data further indicate that both sodium chromate and lead chromate are less cytotoxic and genotoxic to sea lion cells than human cells, based o...

  19. Genotoxic pressure of vineyard pesticides in fish: field and mesocosm surveys.

    Science.gov (United States)

    Bony, S; Gillet, C; Bouchez, A; Margoum, C; Devaux, A

    2008-09-17

    The present study deals with the genotoxicity assessment of vineyard pesticides in fish exposed in the field or in mesocosm conditions. Primary DNA damage was quantified as strand breaks using the single cell gel electrophoresis assay (Comet assay) applied to fish erythrocytes. In a first experiment, a significant genotoxic effect was observed following an upstream-downstream gradient in early life stages of brown trout (Salmo trutta fario) exposed in the Morcille River contaminated by a mixture of vineyard pesticides during three consecutive years. The pronounced response in terms of DNA damage reported in the present study could argue for a high sensitivity of fish early life stage and/or a high level of exposure to genotoxic compounds in the Morcille River. This stresses the interest in using trout larvae incubated in sediment bed to assess genotoxic compounds in the field. In a second experiment, adult European topminnow (Phoxinus phoxinus) were exposed in water running through artificial channels to a mixture of diuron and azoxystrobin, two of the main pesticides detected in the Morcille watershed. As compared with the unexposed channel, a 3-5-fold increase in the DNA damage was observed in fish exposed to chronic environmental pesticide concentrations (1-2 microg L(-1) for diuron and 0.5-1 microg L(-1) for axoxystrobin). A single 6h pulse of pesticide (14 microg L(-1) of diuron and 7 microg L(-1) of azoxystrobin) was applied to simulate transiently elevated chemical concentrations in the river following storm conditions. It did not increase genotoxicity. After a 1-month recovery period, DNA damage in exposed fish erythrocytes recovered to unexposed level, suggesting possible involvement of both repair mechanisms and cellular turnover in this transient response. This work highlights that vineyard treatment by pesticides and in particular diuron and azoxystrobin can represent a genotoxic threat to fish from contaminated watershed rivers. PMID:18703238

  20. DNA dosimetry assessment for sunscreen genotoxic photoprotection.

    Directory of Open Access Journals (Sweden)

    André Passaglia Schuch

    Full Text Available BACKGROUND: Due to the increase of solar ultraviolet radiation (UV incidence over the last few decades, the use of sunscreen has been widely adopted for skin protection. However, considering the high efficiency of sunlight-induced DNA lesions, it is critical to improve upon the current approaches that are used to evaluate protection factors. An alternative approach to evaluate the photoprotection provided by sunscreens against daily UV radiation-induced DNA damage is provided by the systematic use of a DNA dosimeter. METHODOLOGY/PRINCIPAL FINDINGS: The Sun Protection Factor for DNA (DNA-SPF is calculated by using specific DNA repair enzymes, and it is defined as the capacity for inhibiting the generation of cyclobutane pyrimidine dimers (CPD and oxidised DNA bases compared with unprotected control samples. Five different commercial brands of sunscreen were initially evaluated, and further studies extended the analysis to include 17 other products representing various formulations and Sun Protection Factors (SPF. Overall, all of the commercial brands of SPF 30 sunscreens provided sufficient protection against simulated sunlight genotoxicity. In addition, this DNA biosensor was useful for rapidly screening the biological protection properties of the various sunscreen formulations. CONCLUSIONS/SIGNIFICANCE: The application of the DNA dosimeter is demonstrated as an alternative, complementary, and reliable method for the quantification of sunscreen photoprotection at the level of DNA damage.

  1. Genotoxic effects of starvation and dimethoate in haemocytes and midgut gland cells of wolf spider Xerolycosa nemoralis (Lycosidae).

    Science.gov (United States)

    Wilczek, Grażyna; Mędrzak, Monika; Augustyniak, Maria; Wilczek, Piotr; Stalmach, Monika

    2016-06-01

    The aim of this study was to assess the genotoxic effects of starvation and dimethoate (organophosphate insecticide) in female and male wolf spiders Xerolycosa nemoralis (Lycosidae) exposed to the stressors under laboratory conditions. DNA damage was measured in haemocytes and midgut gland cells using the comet assay. In response to the two stressing factors, both cell types showed %TDNA, tail length (TL) and OTM values higher in males than in females. Level of DNA damage in haemocytes was greater than in midgut gland cells. In both sexes, the strongest genotoxicity was recorded at single application of dimethoate. After five-time exposure to the pesticide, genotoxic effects of a single dose were sustained in males and reduced to the control level in females. Starvation stress was well tolerated by the females, in which neither cell type was affected by DNA damage. However, in male haemocytes food deprivation induced severe DNA damage, what suggests suppression of the defence potential at prolonged starvation periods.

  2. Genotoxic and cytotoxic damage by the therapeutic radiopharmaceutical [{sup 166}Dy]Dy/{sup 166}Ho-EDTMP as in vivo generator system; Dano genotoxico y citotoxico por el radiofarmaco terpeutico [{sup 166}Dy]Dy/{sup 166}Ho-EDTMP como sistema de generador in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Pedraza L, M.; Piedras R, J. [Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran. Vasco. de Quiroga 15, 14000 Mexico D.F. (Mexico); Ferro F, G.; Morales R, P. [ININ, Km. 36.5 Carretera Mexico-Toluca, Ocoyoacac, 52045 Estado de Mexico (Mexico); Murphy S, E. [Hospital Santaelena, Mexico D.F. (Mexico); Hernandez O, O. [Escuela Superior de Fisica y Matematicas, IPN, Mexico D.F. (Mexico)

    2005-07-01

    In patients with leukemias and multiple myeloma, the cure can be obtained to inclination of a bone marrow transplant (m.o.), for that which one is used a combination of external radiotherapy and chemotherapy with the consequent toxicity to healthy organs. The complex [{sup 166}Dy]Dy/{sup 166}Ho-ethylenediaminetetramethylenephosphonate ([{sup 166}Dy]Dy/{sup 166}Ho-EDTMP) it forms a generator system in vivo stable with bony selective likeness in mice therefore, this it could work as a therapeutic radiopharmaceutical for bone marrow ablation. The objective of this original work was to determine the genotoxic and cytotoxic damage produced by the [{sup 166}Dy]Dy/{sup 166}Ho-EDTMP like a generator system in vivo by means of the reticulocytes reduction (RET) and micronucleus elevation in reticulocytes (RET-MN) in peripheral blood and to evaluate its myeloablative potential for histopathologic studies. It was irradiated {sup 166}Dy{sub 2}O{sub 3} enriched and it was add in form {sup 166}DyCI{sub 3} to the EDTMP in a softening media of phosphates (pH 8), the optimal molar relationship {sup 166}Dy: EDTMP was 1.7:1 and the radiochemical purity was evaluated by ITLC. The Dy:EDTMP complexes, non radioactive, its were prepared in the same way with non irradiated dysprosium oxide. A group of BALB/c mice was injected intraperitoneally with the radiopharmaceutical and two groups of control mice were injected with the non radioactive complex and with sodium chloride 0.9% respectively. Before injecting each one of the solutions it was take a basal sample of peripheral blood of the mouse tail and each 48 h post-injection during 12 d. The animals were sacrificed to obtain the organs of interest and to determine the radioactivity in each one. The femur was used for the histopathologic studies. The quantification of the frequency of RET and RET-MN was carried out by flow cytometry of the sanguine samples and the Monte Carlo code MCNP4B for the dosimetry calculations was used. The

  3. Genotoxicity test of irradiated foods

    International Nuclear Information System (INIS)

    Safety tests of radiation irradiated foods started as early as from 1967 in Japan and genotoxicity tests in the Hatano Res. Inst., from 1977. The latter is unique in the world and is reviewed in this paper. Tests included those for the initial injury of DNA, mutagenicity, chromosomal aberration and transformation with use of bacteria, cultured mammalian cells and animals (for chromosomal aberration, micronucleus formation and dominant lethality). Foods tested hitherto were onion, rice, wheat and flour, Vienna sausage, fish sausage (kamaboko), mandarian orange, potato, black pepper and red capsicum, of which extract or powder was subjected to the test. Irradiation doses and its purposes were 0.15-6 kGy γ-ray (60Co) or electron beam by the accelerator (only for the orange), and suppression of germination, pesticide action or sterilization, respectively. Genotoxicity of all foods under tested conditions is shown negative. (N.I.)

  4. Genotoxicity evaluation of drinking water sources in human peripheral blood lymphocytes using the comet assay

    Institute of Scientific and Technical Information of China (English)

    WU Yulin; CHEN Haigang; LI Zhaoli; SUN Liwei; QU Mengmeng; LI Mei; KONG Zhiming

    2008-01-01

    The potential harm of organic pollutants in drinking water to human health is widely focused on in the world; more and more pollutants with genotoxic substances are released into the aquatic environment. Water source samples were collected from 7 different localities of Nanjing City. The potential genotoxicity of organic extracts from drinking water sources were investigated by means of the comet assay in human peripheral lymphocytes. The results showed that all the organic extracts from all the water source samples could induce DNA damages of human peripheral blood lymphocytes at different levels. A significant difference (P < 0.01) was observed when compared with the solvent control. The DNA damage increased with the increase of the dosage of the original water source. Significant differences of DNA damage were observed in different drinking water sources, as shown by the multiple comparisons analysis at the dosage of 100×; the degree of DNA damage treated by Hushu waterworks (at town level) was the most serious, the arbitrary units (AU) was 141.62±6.96, however, that of Shangyuanmen waterworks (at city level) was only 109.64±2.97. The analysis also revealed that the genotoxicity of town's water sources was higher than that of the city. The results demonstrated that the comet assay can be successfully applied to the genotoxicity monitoring programs of drinking water sources.

  5. Genotoxicity assessment of amaranth and allura red using Saccharomyces cerevisiae.

    Science.gov (United States)

    Jabeen, Hafiza Sumara; ur Rahman, Sajjad; Mahmood, Shahid; Anwer, Sadaf

    2013-01-01

    Amaranth (E123) and Allura red (E129), very important food azo dyes used in food, drug, paper, cosmetic and textile industries, were assessed for their genotoxic potential through comet assay in yeast cells. Comet assay was standardized by with different concentration of H(2)O(2). Concentrations of Amaranth and Allura red were maintained in sorbitol buffer starting from 9.76 to 5,000 μg/mL and 1 × 10(4) cells were incubated at two different incubation temperatures 28 and 37°C. Amaranth (E123) and Allura red (E129) were found to exhibit their genotoxic effect directly in Saccharomyces cerevisiae. No significant genotoxic activity was observed for Amaranth and Allura red at 28°C but at 37°C direct relation of Amaranth concentration with comet tail was significant and no positive relation was seen with time exposure factor. At 37°C the minimum concentration of Amaranth and Allura red at which significant DNA damage observed through comet assay was 1,250 μg/mL in 2nd h post exposure time. The results indicated that food colors should be carefully used in baking products as heavy concentration of food colors could affect the fermentation process of baking.

  6. Genotoxic and apoptotic effects of Goeckerman therapy for psoriasis

    Energy Technology Data Exchange (ETDEWEB)

    Borska, L.; Andrys, C.; Krejsek, J.; Hamakova, K.; Kremlacek, J.; Palicka, V.; Ranna, D.; Fiala, Z. [Charles University Prague, Prague (Czech Republic). Faculty of Medicine

    2010-03-15

    Goeckerman therapy (GT) for psoriasis is based on cutaneous application of crude coal tar (polycyclic aromatic hydrocarbons (PAH)) and exposure to ultraviolet radiation (UVR). PAH and UVR are mutagenic, carcinogenic and immunotoxic agents that promote apoptosis. We evaluated dermal absorption of PAH as well as the genotoxic and apoptotic effects of GT in 20 patients with psoriasis, by determining numbers of chromosomal abnormalities in peripheral lymphocytes, and levels of 1-hydroxypyrene (1-OHP), p53 protein and soluble FasL (sFasL) in urine and/or blood, before and after GT. Psoriasis Area and Severity Index (PASI) score was used to evaluate clinical efficacy of GT. Compared with pre-treatment levels, there was a significant increase in urine 1-OHP, indicating a high degree of dermal absorption of PAH (P <0.01). We also found a significant increase in the number of chromosomal abnormalities in peripheral blood lymphocytes (P <0.001), suggesting that GT is genotoxic; significantly increased p53 protein in plasma (P <0.05), an indicator of cell response to DNA damage; and significantly increased sFasL in serum (P <0.01), an indicator of apoptosis. The PASI score was significantly decreased after GT (P <0.001), confirming clinical benefit of this treatment. Our results demonstrate high dermal absorption of PAH during GT and provide evidence that GT promotes genotoxicity and apoptosis.

  7. Neurobehavioral and genotoxic evaluation of (-)-linalool in mice.

    Science.gov (United States)

    Coelho, Vanessa; Mazzardo-Martins, Leidiane; Martins, Daniel Fernandes; Santos, Adair Roberto Soares; da Silva Brum, Lucimar Filot; Picada, Jaqueline Nascimento; Pereira, Patrícia

    2013-10-01

    (-)-Linalool is a monoterpene compound commonly found as a major component of the essential oil of several aromatic species. It has been shown to exert several actions in the central nervous system (CNS) and is able to inhibit glutamate receptors. This study investigated the effect of (-)-linalool in depression and genotoxicity models. Mice were given (-)-linalool (10, 50, 100 or 200 mg/kg i.p.) and were evaluated using the tail suspension test (TST). Genotoxic and antigenotoxic effects in blood and brain were investigated using the alkaline comet assay. In the TST, the animals that received doses of 100 and 200 mg/kg presented a decrease in immobility times. No increase in DNA damage was observed in either tissue, and resistance to DNA oxidative damage induced by hydrogen peroxide did not increase. (-)-Linalool showed an antidepressant-like activity in the TST and was unable to cause damage/protection to DNA in brain tissue and peripheral blood. This investigation provides evidence of an important effect of (-)-linalool on the CNS; however, more studies are necessary to support its possible clinical uses.

  8. Nanoceria have no genotoxic effect on human lens epithelial cells

    Science.gov (United States)

    Pierscionek, Barbara K.; Li, Yuebin; Yasseen, Akeel A.; Colhoun, Liza M.; Schachar, Ronald A.; Chen, Wei

    2010-01-01

    There are no treatments for reversing or halting cataract, a disease of the structural proteins in the eye lens, that has associations with other age-related degenerative conditions such as Alzheimer's disease. The incidence of cataract and associated conditions is increasing as the average age of the population rises. Protein folding diseases are difficult to assess in vivo as proteins and their age-related changes are assessed after extraction. Nanotechnology can be used to investigate protein changes in the intact lens as well as for a potential means of drug delivery. Nanoparticles, such as cerium oxide (CeO2) which have antioxidant properties, may even be used as a means of treating cataract directly. Prior to use in treatments, nanoparticle genotoxicity must be tested to assess the extent of any DNA or chromosomal damage. Sister chromatid exchanges were measured and DNA damage investigated using the alkaline COMET assay on cultured human lens epithelial cells, exposed to 5 and 10 µg ml-1 of CeO2 nanoparticles (nanoceria). Nanoceria at these dosages did not cause any DNA damage or significant increases in the number of sister chromatid exchanges. The absence of genotoxic effects on lens cells suggests that nanoceria, in the doses and exposures tested in this study, are not deleterious to the eye lens and have the potential for use in studying structural alterations, in developing non-surgical cataract treatments and in investigating other protein folding diseases.

  9. Nanoceria have no genotoxic effect on human lens epithelial cells

    International Nuclear Information System (INIS)

    There are no treatments for reversing or halting cataract, a disease of the structural proteins in the eye lens, that has associations with other age-related degenerative conditions such as Alzheimer's disease. The incidence of cataract and associated conditions is increasing as the average age of the population rises. Protein folding diseases are difficult to assess in vivo as proteins and their age-related changes are assessed after extraction. Nanotechnology can be used to investigate protein changes in the intact lens as well as for a potential means of drug delivery. Nanoparticles, such as cerium oxide (CeO2) which have antioxidant properties, may even be used as a means of treating cataract directly. Prior to use in treatments, nanoparticle genotoxicity must be tested to assess the extent of any DNA or chromosomal damage. Sister chromatid exchanges were measured and DNA damage investigated using the alkaline COMET assay on cultured human lens epithelial cells, exposed to 5 and 10 μg ml-1 of CeO2 nanoparticles (nanoceria). Nanoceria at these dosages did not cause any DNA damage or significant increases in the number of sister chromatid exchanges. The absence of genotoxic effects on lens cells suggests that nanoceria, in the doses and exposures tested in this study, are not deleterious to the eye lens and have the potential for use in studying structural alterations, in developing non-surgical cataract treatments and in investigating other protein folding diseases.

  10. In vivo genotoxicity assessment of acrylamide and glycidyl methacrylate.

    Science.gov (United States)

    Dobrovolsky, Vasily N; Pacheco-Martinez, M Monserrat; McDaniel, L Patrice; Pearce, Mason G; Ding, Wei

    2016-01-01

    Acrylamide (ACR) and glycidyl methacrylate (GMA) are structurally related compounds used for making polymers with various properties. Both chemicals can be present in food either as a byproduct of processing or a constituent of packaging. We performed a comprehensive evaluation of ACR and GMA genotoxicity in Fisher 344 rats using repeated gavage administrations. Clastogenicity was measured by scoring micronucleated (MN) erythrocytes from peripheral blood, DNA damage in liver, bone marrow and kidneys was measured using the Comet assay, and gene mutation was measured using the red blood cell (RBC) and reticulocyte Pig-a assay. A limited histopathology evaluation was performed in order to determine levels of cytotoxicity. Doses of up to 20 mg/kg/day of ACR and up to 250 mg/kg/day of GMA were used. ACR treatment resulted in DNA damage in the liver, but not in the bone marrow. While ACR was not a clastogen, it was a weak (equivocal) mutagen in the cells of bone marrow. GMA caused DNA damage in the cells of bone marrow, liver and kidney, and induced MN reticulocytes and Pig-a mutant RBCs in a dose-dependent manner. Collectively, our data suggest that both compounds are in vivo genotoxins, but the genotoxicity of ACR is tissue specific.

  11. Nanoceria have no genotoxic effect on human lens epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Pierscionek, Barbara K; Yasseen, Akeel A [School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA (United Kingdom); Li, Yuebin; Schachar, Ronald A; Chen, Wei [Department of Physics, University of Texas at Arlington, Arlington, TX 76019 (United States); Colhoun, Liza M, E-mail: b.pierscionek@ulster.ac.uk, E-mail: weichen@uta.edu [Centre for Vision and Vascular Sciences, School of Medicine, Dentistry and Biomedical Sciences, Queen' s University Belfast, Grosvenor Road, Belfast, BT12 6BA (United Kingdom)

    2010-01-22

    There are no treatments for reversing or halting cataract, a disease of the structural proteins in the eye lens, that has associations with other age-related degenerative conditions such as Alzheimer's disease. The incidence of cataract and associated conditions is increasing as the average age of the population rises. Protein folding diseases are difficult to assess in vivo as proteins and their age-related changes are assessed after extraction. Nanotechnology can be used to investigate protein changes in the intact lens as well as for a potential means of drug delivery. Nanoparticles, such as cerium oxide (CeO{sub 2}) which have antioxidant properties, may even be used as a means of treating cataract directly. Prior to use in treatments, nanoparticle genotoxicity must be tested to assess the extent of any DNA or chromosomal damage. Sister chromatid exchanges were measured and DNA damage investigated using the alkaline COMET assay on cultured human lens epithelial cells, exposed to 5 and 10 {mu}g ml{sup -1} of CeO{sub 2} nanoparticles (nanoceria). Nanoceria at these dosages did not cause any DNA damage or significant increases in the number of sister chromatid exchanges. The absence of genotoxic effects on lens cells suggests that nanoceria, in the doses and exposures tested in this study, are not deleterious to the eye lens and have the potential for use in studying structural alterations, in developing non-surgical cataract treatments and in investigating other protein folding diseases.

  12. Current regulatory perspectives on genotoxicity testing for botanical drug product development in the U.S.A.

    Science.gov (United States)

    Wu, Kuei-Meng; Dou, Jinhui; Ghantous, Hanan; Chen, Shaw; Bigger, Anita; Birnkrant, Debra

    2010-02-01

    Genotoxicity testing is an important part of preclinical safety assessment of new drugs and is required prior to Phase I/II clinical trials. It is designed to detect genetic damage such as gene mutations and chromosomal aberration, which may be reflected in tumorigenic or heritable mutation potential of the drug. Botanical new drugs in the U.S. are entitled to a waiver for preclinical pharmacology/toxicology studies, including genotoxicity testing, in support of an initial clinical trial under IND, contingent on previous human experience. Recently, ethical concerns have been raised over conducting Phase I/II clinical trials of new drugs with positive genotoxicity findings in healthy volunteers. Although the relevance of this issue to patients, as opposed to healthy volunteers, depends on the drug's indication, duration of treatment, and specific findings related to the assays, the regulatory view is to avoid exposing patients to genotoxic compounds unnecessarily in clinical trials. This philosophy may impact on herbal supplement marketing and botanical drug development, in that genotoxicity data are often lacking while consumers are exposed to the herbal supplement, or healthy volunteers are tested in an initial Phase I/II clinical trial on the botanical drug. This paper presents results of a survey conducted on genotoxicity data in botanical INDs submitted to the Agency and discusses the significance of this information. The information presented indicates that the sponsors of botanical INDs have increasingly recognized the importance of genotoxicity information and may have prioritized its acquisition in their strategic drug development programs.

  13. Genotoxic thresholds, DNA repair, and susceptibility in human populations

    International Nuclear Information System (INIS)

    It has been long assumed that DNA damage is induced in a linear manner with respect to the dose of a direct acting genotoxin. Thus, it is implied that direct acting genotoxic agents induce DNA damage at even the lowest of concentrations and that no 'safe' dose range exists. The linear (non-threshold) paradigm has led to the one-hit model being developed. This 'one hit' scenario can be interpreted such that a single DNA damaging event in a cell has the capability to induce a single point mutation in that cell which could (if positioned in a key growth controlling gene) lead to increased proliferation, leading ultimately to the formation of a tumour. There are many groups (including our own) who, for a decade or more, have argued, that low dose exposures to direct acting genotoxins may be tolerated by cells through homeostatic mechanisms such as DNA repair. This argument stems from the existence of evolutionary adaptive mechanisms that allow organisms to adapt to low levels of exogenous sources of genotoxins. We have been particularly interested in the genotoxic effects of known mutagens at low dose exposures in human cells and have identified for the first time, in vitro genotoxic thresholds for several mutagenic alkylating agents (Doak et al., 2007). Our working hypothesis is that DNA repair is primarily responsible for these thresholded effects at low doses by removing low levels of DNA damage but becoming saturated at higher doses. We are currently assessing the roles of base excision repair (BER) and methylguanine-DNA methyltransferase (MGMT) for roles in the identified thresholds (Doak et al., 2008). This research area is currently important as it assesses whether 'safe' exposure levels to mutagenic chemicals can exist and allows risk assessment using appropriate safety factors to define such exposure levels. Given human variation, the mechanistic basis for genotoxic thresholds (e.g. DNA repair) has to be well defined in order that susceptible individuals are

  14. Genotoxicity and Mutagenicity of Suspended Particulate Matter of River Water and Waste Water Samples

    Directory of Open Access Journals (Sweden)

    Georg Reifferscheid

    2002-01-01

    Full Text Available Suspended particulate matter of samples of river water and waste water treatment plants was tested for genotoxicity and mutagenicity using the standardized umu assay and two versions of the Ames microsuspension assay. The study tries to determine the entire DNA-damaging potential of the water samples and the distribution of DNA-damaging substances among the liquid phase and solid phase. Responsiveness and sensitivity of the bioassays are compared.

  15. Genotoxicity and Mutagenicity of Suspended Particulate Matter of River Water and Waste Water Samples

    OpenAIRE

    Georg Reifferscheid; Oepen, Britta v.

    2002-01-01

    Suspended particulate matter of samples of river water and waste water treatment plants was tested for genotoxicity and mutagenicity using the standardized umu assay and two versions of the Ames microsuspension assay. The study tries to determine the entire DNA-damaging potential of the water samples and the distribution of DNA-damaging substances among the liquid phase and solid phase. Responsiveness and sensitivity of the bioassays are compared.

  16. Genotoxicity of industrial wastes and effluents.

    Science.gov (United States)

    Claxton, L D; Houk, V S; Hughes, T J

    1998-06-01

    In excess of several million pounds of genotoxic and/or carcinogenic industrial wastes are released into the U.S. environment each year. Chemical characterization of these waste materials can rarely provide an adequate assessment of their genotoxicity and potential hazard. Bioassays do not require prior information about chemical composition and can effectively assess the genotoxicity of complex waste materials. The most commonly used genotoxicity assay has been the Salmonella mutagenicity assay. Results with this system have shown that the genotoxic potency of industrial wastes can vary over 10 orders of magnitude, from virtually nondetectable to highly potent. Industries employing similar industrial processes generally release wastes of similar potency. Extremely high potency wastes include those from furazolidone and nitrofurfural production. Pulp and paper mills, steel foundries, and organic chemical manufacturing facilities also discharge wastes of noteworthy potency. Treatment and remediation of some wastes, such as pulp and paper mill effluents, have been shown to reduce or eliminate genotoxicity. However, in other cases, treatment and remediation have been shown to enhance genotoxicity, such as for fungal treatment of oils. Analyses of samples collected from areas known to receive industrial wastes and effluents have shown that genotoxins can accumulate in the receiving environment and have adverse effects on indigenous biota. The evaluation of hazardous wastes and effluents by genotoxicity assays may provide data useful not only for hazard identification but for comparative risk assessment.

  17. Sam68/KHDRBS1 is critical for colon tumorigenesis by regulating genotoxic stress-induced NF-κB activation.

    Science.gov (United States)

    Fu, Kai; Sun, Xin; Wier, Eric M; Hodgson, Andrea; Liu, Yue; Sears, Cynthia L; Wan, Fengyi

    2016-01-01

    Nuclear factor kappa B (NF-κB)-mediated transcription is an important mediator for cellular responses to DNA damage. Genotoxic agents trigger a 'nuclear-to-cytoplasmic' NF-κB activation signaling pathway; however, the early nuclear signaling cascade linking DNA damage and NF-κB activation is poorly understood. Here we report that Src-associated-substrate-during-mitosis-of-68kDa/KH domain containing, RNA binding, signal transduction associated 1 (Sam68/KHDRBS1) is a key NF-κB regulator in genotoxic stress-initiated signaling pathway. Sam68 deficiency abolishes DNA damage-stimulated polymers of ADP-ribose (PAR) production and the PAR-dependent NF-κB transactivation of anti-apoptotic genes. Sam68 deleted cells are hypersensitive to genotoxicity caused by DNA damaging agents. Upregulated Sam68 coincides with elevated PAR production and NF-κB-mediated anti-apoptotic transcription in human and mouse colon cancer. Knockdown of Sam68 sensitizes human colon cancer cells to genotoxic stress-induced apoptosis and genetic deletion of Sam68 dampens colon tumor burden in mice. Together our data reveal a novel function of Sam68 in the genotoxic stress-initiated nuclear signaling, which is crucial for colon tumorigenesis. PMID:27458801

  18. Genotoxic effects of zinc oxide nanoparticles

    Science.gov (United States)

    Heim, Julia; Felder, Eva; Tahir, Muhammad Nawaz; Kaltbeitzel, Anke; Heinrich, Ulf Ruediger; Brochhausen, Christoph; Mailänder, Volker; Tremel, Wolfgang; Brieger, Juergen

    2015-05-01

    The potential toxicity of nanoparticles has currently provoked public and scientific discussions, and attempts to develop generally accepted handling procedures for nanoparticles are under way. The investigation of the impact of nanoparticles on human health is overdue and reliable test systems accounting for the special properties of nanomaterials must be developed. Nanoparticular zinc oxide (ZnO) may be internalised through ambient air or the topical application of cosmetics, only to name a few, with unpredictable health effects. Therefore, we analysed the determinants of ZnO nanoparticle (NP) genotoxicity. ZnO NPs (15-18 nm in diameter) were investigated at concentrations of 0.1, 10 and 100 μg mL-1 using the cell line A549. Internalised NPs were only infrequently detectable by TEM, but strongly increased Zn2+ levels in the cytoplasm and even more in the nuclear fraction, as measured by atom absorption spectroscopy, indicative of an internalised zinc and nuclear accumulation. We observed a time and dosage dependent reduction of cellular viability after ZnO NP exposure. ZnCl2 exposure to cells induced similar impairments of cellular viability. Complexation of Zn2+ with diethylene triamine pentaacetic acid (DTPA) resulted in the loss of toxicity of NPs, indicating the relevant role of Zn2+ for ZnO NP toxicity. Foci analyses showed the induction of DNA double strand breaks (DSBs) by ZnO NPs and increased intracellular reactive oxygen species (ROS) levels. Treatment of the cells with the ROS scavenger N-acetyl-l-cysteine (NAC) resulted in strongly decreased intracellular ROS levels and reduced DNA damage. However, a slow increase of ROS after ZnO NP exposure and reduced but not quashed DSBs after NAC-treatment suggest that Zn2+ may exert genotoxic activities without the necessity of preceding ROS-induction. Our data indicate that ZnO NP toxicity is a result of cellular Zn2+ intake. Subsequently increased ROS-levels cause DNA damage. However, we found evidence for

  19. Genotoxic effect of Phenanthrene on Chironomus sancticaroli (Diptera: Chironomidae

    Directory of Open Access Journals (Sweden)

    Gisele dos Santos Morais

    2014-08-01

    Full Text Available Phenanthrene, a Polycyclic Aromatic Hydrocarbon, remains adsorbed to sedimentary particles in aquatic environments. It affects mainly benthic organisms, and is considered potentially genotoxic. In ecotoxicology, species of Chironomus Meigen, 1803 are widely known as bioindicators of the effects of chemicals on aquatic organisms. This study investigates the effects of phenanthrene on the size of the head capsule of Chironomus sancticaroli Strixino & Strixino, 1981 larvae after chronic (eight days exposure, and DNA damage after acute (96 hours and chronic exposure (eight days, under laboratory conditions. DNA damage, evaluated using the alkaline comet assay, detected effects for both exposure periods, indicating that phenanthrene is toxic for C. sancticaroli. For the acute exposure, we analyzed five concentrations of phenanthrene, between 0.16 mg.l-1 and 1.60 mg.l-1, detecting significant differences (Kruskall-Wallis test with p < 0.05 in the degree of DNA damage in all groups. These effects were not dose-dependent. For the chronic exposure, two concentrations (0.16 mg.l-1, 0.83 mg.l-1 were analyzed, and DNA damage was observed in both. Again, the effects were not dose-dependent. This indicates that phenanthrene is genotoxic to larvae of C. sancticaroli even at low concentrations. The size of the head capsule was evaluated after chronic exposure to concentrations of 0.16 mg.l-1 and 0.83 mg.l-1. Significant differences (ANOVA test with p < 0.05 were detected in the two concentrations, and a reduction in the size of the larval head capsule was observed. This suggests that phenanthrene causes delay in larval development. These results indicate that phenanthrene affects the development of and causes DNA damage in C. sancticaroli larvae. Therefore, we suggest that C. sancticaroli can be used as a biological indicator for environmental contamination with phenanthrene.

  20. Mutagenic and genotoxic activity of particulate matter MP2,5, in Pamplona, North Santander, Colombia

    Directory of Open Access Journals (Sweden)

    Martínez Montañez, Mónica Liseth

    2012-10-01

    Full Text Available Objective: To study the mutagenic and genotoxic activities of particulate material (MP2,5 collected in Pamplona, Norte de Santander, Colombia.Materials and methods: MP2,5 was monitored by means of a Partisol 2025 sequential air sampler with Plus Palmflex quartz filters. The latter were subjected to two extraction procedures: Soxhlet extraction using dichloromethane-acetone; and ultrasonic extraction using dichloromethane, acetone and dichloromethane/ acetone mix. The mutagenic and genotoxic activities were determined for each extract.Results: This is the first study conducted in Colombia that reports the mutagenic and genotoxic activities associated with particulate matter (MP2,5 taken from vehicular emissions in Pamplona, Norte de Santander. The mutagenic assay determined by the Ames test using Salmonella typhimurium strains TA98 and TA100 showed a high direct mutagenic activity in the analyzed extracts. On the other hand, the genotoxic activity, determined by means of the comet assay, was high too.Conclusion: Particulate material (MP2,5 present in air samples in Pamplona (northeastern Colombia is a risk factor for the exposed population because it can directly induce mutations and also cause genotoxic damage.

  1. In vitro and in vivo genotoxic effects of straight versus tangled multi-walled carbon nanotubes.

    Science.gov (United States)

    Catalán, Julia; Siivola, Kirsi M; Nymark, Penny; Lindberg, Hanna; Suhonen, Satu; Järventaus, Hilkka; Koivisto, Antti J; Moreno, Carlos; Vanhala, Esa; Wolff, Henrik; Kling, Kirsten I; Jensen, Keld Alstrup; Savolainen, Kai; Norppa, Hannu

    2016-08-01

    Some multi-walled carbon nanotubes (MWCNTs) induce mesothelioma in rodents, straight MWCNTs showing a more pronounced effect than tangled MWCNTs. As primary and secondary genotoxicity may play a role in MWCNT carcinogenesis, we used a battery of assays for DNA damage and micronuclei to compare the genotoxicity of straight (MWCNT-S) and tangled MWCNTs (MWCNT-T) in vitro (primary genotoxicity) and in vivo (primary or secondary genotoxicity). C57Bl/6 mice showed a dose-dependent increase in DNA strand breaks, as measured by the comet assay, in lung cells 24 h after a single pharyngeal aspiration of MWCNT-S (1-200 μg/mouse). An increase was also observed for DNA strand breaks in lung and bronchoalveolar lavage (BAL) cells and for micronucleated alveolar type II cells in mice exposed to aerosolized MWCNT-S (8.2-10.8 mg/m(3)) for 4 d, 4 h/d. No systemic genotoxic effects, assessed by the γ-H2AX assay in blood mononuclear leukocytes or by micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow or blood, were observed for MWCNT-S by either exposure technique. MWCNT-T showed a dose-related decrease in DNA damage in BAL and lung cells of mice after a single pharyngeal aspiration (1-200 μg/mouse) and in MNPCEs after inhalation exposure (17.5 mg/m(3)). In vitro in human bronchial epithelial BEAS-2B cells, MWCNT-S induced DNA strand breaks at low doses (5 and 10 μg/cm(2)), while MWCNT-T increased strand breakage only at 200 μg/cm(2). Neither of the MWCNTs was able to induce micronuclei in vitro. Our findings suggest that both primary and secondary mechanisms may be involved in the genotoxicity of straight MWCNTs. PMID:26674712

  2. Dose-Response Assessment of Four Genotoxic Chemicals in a Combined Mouse and Rat Micronucleus and Comet Assay Protocol

    OpenAIRE

    Recio, Leslie; Hobbs, Cheryl; Caspary, William; Witt, Kristine L.

    2010-01-01

    The in vivo micronucleus (MN) assay has proven to be an effective measure of genotoxicity potential. However, sampling a single tissue (bone marrow) for a single indicator of genetic damage using the MN assay provides a limited genotoxicity profile. The in vivo alkaline (pH>13) Comet assay, which detects a broad spectrum of DNA damage, can be applied to a variety of rodent tissues following administration of test agents. To determine if the Comet assay is a useful supplement to the in vivo MN...

  3. Genotoxicity monitoring of freshwater environments using caged carp (Cyprinus carpio).

    Science.gov (United States)

    Klobucar, Göran I V; Stambuk, Anamaria; Pavlica, Mirjana; Sertić Perić, Mirela; Kutuzović Hackenberger, Branimir; Hylland, Ketil

    2010-01-01

    The present study deals with genotoxicity assessment of freshwaters using caged carp (Cyprinus carpio). Carps were transplanted from a fish-farm to three differently polluted sites in eastern Croatia. Two polluted sites were situated in the river Drava, downstream from the cities of Belisće and Osijek, while the reference site was in the Nature Park Kopacki rit, a preserved wetland area with limited anthropogenic influence. Exposure lasted for 3 weeks and was repeated for 3 years (2002-2004). DNA damage was assessed in erythrocytes of the exposed animals by the Comet assay and micronucleus test (MNT). In order to evaluate possible differences in stress responses to polluted water in situ and in aquaria a laboratory exposure was performed with water from the studied location in the second year of the study. Carp from the sites with high anthropogenic influence (Belisće and Osijek) had higher average DNA damage as expressed in both the MNT and Comet assay. Of the two, the Comet assay appeared to be more sensitive following both caging and aquaria exposures. The results from this study suggest that 3 weeks caging exposure of C. carpio may be a useful strategy to monitor for genotoxic agents in freshwater ecosystems. PMID:19626438

  4. Evaluation of environmental genotoxicity by comet assay in Columba livia.

    Science.gov (United States)

    González-Acevedo, Anahi; García-Salas, Juan A; Gosálvez, Jaime; Fernández, José Luis; Dávila-Rodríguez, Martha I; Cerda-Flores, Ricardo M; Méndez-López, Luis F; Cortés-Gutiérrez, Elva I

    2016-01-01

    The concentrations of recognized or suspected genotoxic and carcinogenic agents found in the air of large cities and, in particular, developing countries, have raised concerns about the potential for chronic health effects in the populations exposed to them. The biomonitoring of environmental genotoxicity requires the selection of representative organisms as "sentinels," as well as the development of suitable and sensitive assays, such as those aimed at assessing DNA damage. The aim of this study was to evaluate DNA damage levels in erythrocytes from Columba livia living in the metropolitan area of Monterrey, Mexico, compared with control animals via comet assay, and to confirm the results via Micronuclei test (MN) and DNA breakage detection-fluorescence in situ hybridization (DBD-FISH). Our results showed a significant increase in DNA migration in animals from the area assayed compared with that observed in control animals sampled in non-contaminated areas. These results were confirmed by MN test and DBD-FISH. In conclusion, these observations confirm that the examination of erythrocytes from Columba livia via alkaline comet assay provides a sensitive and reliable end point for the detection of environmental genotoxicants.

  5. Early Genotoxic and Cytotoxic Effects of the Toxic Dinoflagellate Prorocentrum lima in the Mussel Mytilus galloprovincialis

    Science.gov (United States)

    Prego-Faraldo, María Verónica; Valdiglesias, Vanessa; Laffon, Blanca; Mendez, Josefina; Eirin-Lopez, Jose M.

    2016-01-01

    Okadaic acid (OA) and dinophysistoxins (DTXs) are the main toxins responsible for diarrhetic shellfish poisoning (DSP) intoxications during harmful algal blooms (HABs). Although the genotoxic and cytotoxic responses to OA have been evaluated in vitro, the in vivo effects of these toxins have not yet been fully explored. The present work fills this gap by evaluating the in vivo effects of the exposure to the DSP-toxin-producing dinoflagellate Prorocentrum lima during the simulation of an early HAB episode in the mussel Mytilus galloprovincialis. The obtained results revealed that in vivo exposure to this toxic microalgae induced early genotoxicity in hemocytes, as a consequence of oxidative DNA damage. In addition, the DNA damage observed in gill cells seems to be mainly influenced by exposure time and P. lima concentration, similarly to the case of the oxidative damage found in hemocytes exposed in vitro to OA. In both cell types, the absence of DNA damage at low toxin concentrations is consistent with the notion suggesting that this level of toxicity does not disturb the antioxidant balance. Lastly, in vivo exposure to growing P. lima cell densities increased apoptosis but not necrosis, probably due to the presence of a high number of protein apoptosis inhibitors in molluscs. Overall, this work sheds light into the in vivo genotoxic and cytotoxic effects of P. lima. In doing so, it also demonstrates for the first time the potential of the modified (OGG1) comet assay for assessing oxidative DNA damage caused by marine toxins in marine invertebrates. PMID:27231936

  6. Early Genotoxic and Cytotoxic Effects of the Toxic Dinoflagellate Prorocentrum lima in the Mussel Mytilus galloprovincialis

    Directory of Open Access Journals (Sweden)

    María Verónica Prego-Faraldo

    2016-05-01

    Full Text Available Okadaic acid (OA and dinophysistoxins (DTXs are the main toxins responsible for diarrhetic shellfish poisoning (DSP intoxications during harmful algal blooms (HABs. Although the genotoxic and cytotoxic responses to OA have been evaluated in vitro, the in vivo effects of these toxins have not yet been fully explored. The present work fills this gap by evaluating the in vivo effects of the exposure to the DSP-toxin-producing dinoflagellate Prorocentrum lima during the simulation of an early HAB episode in the mussel Mytilus galloprovincialis. The obtained results revealed that in vivo exposure to this toxic microalgae induced early genotoxicity in hemocytes, as a consequence of oxidative DNA damage. In addition, the DNA damage observed in gill cells seems to be mainly influenced by exposure time and P. lima concentration, similarly to the case of the oxidative damage found in hemocytes exposed in vitro to OA. In both cell types, the absence of DNA damage at low toxin concentrations is consistent with the notion suggesting that this level of toxicity does not disturb the antioxidant balance. Lastly, in vivo exposure to growing P. lima cell densities increased apoptosis but not necrosis, probably due to the presence of a high number of protein apoptosis inhibitors in molluscs. Overall, this work sheds light into the in vivo genotoxic and cytotoxic effects of P. lima. In doing so, it also demonstrates for the first time the potential of the modified (OGG1 comet assay for assessing oxidative DNA damage caused by marine toxins in marine invertebrates.

  7. Human Genotoxic Study Carried Out Two Years after Oil Exposure during the Clean-up Activities Using Two Different Biomarkers

    Directory of Open Access Journals (Sweden)

    Gloria Biern

    2015-11-01

    Full Text Available Micronuclei, comet and chromosome alterations assays are the most widely used biomarkers for determining the genotoxic damage in a population exposed to genotoxic chemicals. While chromosome alterations are an excellent biomarker to detect short- and long-term genotoxic effects, the comet assay only measures early biological effects, and furthermore it is unknown whether nuclear abnormalies, such as those measured in the micronucleus test, remain detectable long-term after an acute exposure. In our previous study, an increase in structural chromosome alterations in fishermen involved in the clean-up of the Prestige oil spill, two years after acute exposure, was detected. The aim of this study is to investigate whether, in lymphocytes from peripheral blood, the nuclear abnormalies (micronucleus, nucleoplasmic bridges and nuclear buds have a similar sensitivity to the chromosome damage analysis for genotoxic detection two years after oil exposure in the same non-smoker individuals and in the same peripheral blood extraction. No significant differences in nuclear abnormalies frequencies between exposed and non-exposed individuals were found (p > 0.05. However, chromosome damage, in the same individuals, was higher in exposed vs. non-exposed individuals, especially for chromosome lesions (p < 0.05. These findings, despite the small sample size, suggest that nuclear abnormalities are probably less-successful biomarkers than are chromosome alterations to evaluate genotoxic effects two or more years after an exposure to oil. Due to the great advantage of micronucleus automatic determination, which allows for a rapid study of hundreds of individuals exposed to genotoxic chemical exposure, further studies are needed to confirm whether this assay is or is not useful in long-term genotoxic studies after the toxic agent is no longer present.

  8. Using DNA damage to monitor water environment

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    DNA damage of aquatic organisms living in polluted environments can be used as a biomarker of the genotoxicity of toxic agents to organisms. This technique has been playing an important role in ecotoxicological study and environmental risk assessment. In this article, main types of DNA damage caused by pollutants in water environments were reviewed; methods of detecting DNA damage were also documented for water environmental monitoring.

  9. Assessing the genotoxicity of urban air pollutants using two in situ plant bioassays

    Energy Technology Data Exchange (ETDEWEB)

    Villarini, M.; Fatigoni, C.; Dominici, L.; Maestri, S. [Department of Medical-Surgical Specialties and Public Health, University of Perugia, I-06126 (Italy); Ederli, L.; Pasqualini, S. [Department of Applied Biology, University of Perugia, I-06121 (Italy); Monarca, S. [Department of Medical-Surgical Specialties and Public Health, University of Perugia, I-06126 (Italy); Moretti, M., E-mail: massimo.moretti@unipg.i [Department of Medical-Surgical Specialties and Public Health, University of Perugia, I-06126 (Italy)

    2009-12-15

    Genotoxicity of urban air has been analysed almost exclusively in airborne particulates. We monitored the genotoxic effects of airborne pollutants in the urban air of Perugia (Central Italy). Two plant bioindicators with different genetic endpoints were used: micronuclei in meiotic pollen mother cells using Tradescantia-micronucleus bioassay (Trad-MCN) and DNA damage in nuclei of Nicotiana tabacum leaves using comet assay (Nicotiana-comet). Buds of Tradescantia clone no. 4430 and young N. tabacum cv. Xanthi plants were exposed for 24 h at three sites with different pollution levels. One control site (indoor control) was also used. The two bioassays showed different sensitivities toward urban pollutants: Trad-MCN assay was the most sensitive, but DNA damage in N. tabacum showed a better correlation with the pollutant concentrations. In situ biomonitoring of airborne genotoxins using higher plants combined with chemical analysis is thus recommended for characterizing genotoxicity of urban air. - Plant bioassays used to explore in situ the correlation between air pollution and genotoxicity.

  10. Cytotoxicity and genotoxicity of intravitreal adalimumab administration in rabbit retinal cells

    Directory of Open Access Journals (Sweden)

    Álcio Coutinho de Paula

    2015-04-01

    Full Text Available Purpose: To assess the cytotoxicity and genotoxicity of intravitreal adalimumab treatment in an animal experimental model using cytological and molecular techniques. Methods: Eighteen rabbits were randomly assigned to three groups: control, adalimumab treatment, and placebo. Cytotoxicity on retinal cells was evaluated using flow cytometry assays to determine the level of apoptosis and necrosis. Genotoxicity was evaluated by comet assays to assess DNA damage, and quantitative real-time polymerase chain reaction (qPCR was used to evaluate expression of apoptosis-inducing caspases (8 and 3. Results: No cytotoxicity or genotoxicity was observed in any of the two treatment groups (adalimumab and placebo following intravitreal administration compared with the control group. Flow cytometry analysis revealed that more than 90% of the cells were viable, and only a low proportion of retinal cells presented apoptotic (~10% or necrotic (<1% activity across all groups. Molecular damage was also low with a maximum of 6.4% DNA degradation observed in the comet assays. In addition, no increase in gene expression of apoptosis-inducing caspases was observed on retinal cells by qPCR in both the adalimumab and placebo groups compared with the control group. Conclusion: The use of adalimumab resulted in no detectable cytotoxicity or genotoxicity on retinal cells for up to 60 days upon administration. These results therefore indicate that adalimumab may be a safe option for intravitreal application to treat ocular inflammatory diseases in which TNF-α is involved.

  11. Cytostatic and genotoxic effect of temephos in human lymphocytes and HepG2 cells.

    Science.gov (United States)

    Benitez-Trinidad, A B; Herrera-Moreno, J F; Vázquez-Estrada, G; Verdín-Betancourt, F A; Sordo, M; Ostrosky-Wegman, P; Bernal-Hernández, Y Y; Medina-Díaz, I M; Barrón-Vivanco, B S; Robledo-Marenco, M L; Salazar, A M; Rojas-García, A E

    2015-06-01

    Temephos is an organophosphorus pesticide that is used in control campaigns against Aedes aegypti mosquitoes, which transmit dengue. In spite of the widespread use of temephos, few studies have examined its genotoxic potential. The aim of this study was to evaluate the cytotoxic, cytostatic and genotoxic effects of temephos in human lymphocytes and hepatoma cells (HepG2). The cytotoxicity was evaluated with simultaneous staining (FDA/EtBr). The cytostatic and genotoxic effects were evaluated using comet assays and the micronucleus technique. We found that temephos was not cytotoxic in either lymphocytes or HepG2 cells. Regarding the cytostatic effect in human lymphocytes, temephos (10 μM) caused a significant decrease in the percentage of binucleated cells and in the nuclear division index as well as an increase in the apoptotic cell frequency, which was not the case for HepG2 cells. The comet assay showed that temephos increased the DNA damage levels in human lymphocytes, but it did not increase the MN frequency. In contrast, in HepG2 cells, temephos increased the tail length, tail moment and MN frequency in HepG2 cells compared to control cells. In conclusion, temephos causes stable DNA damage in HepG2 cells but not in human lymphocytes. These findings suggest the importance of temephos biotransformation in its genotoxic effect. PMID:25746384

  12. Genotoxicity in Oreochromis niloticus (Cichlidae) induced by Microcystis spp bloom extract containing microcystins.

    Science.gov (United States)

    da Silva, R R Pavan; Pires, O R; Grisolia, C K

    2011-09-01

    Studies of genotoxicity in fish caused by cyanobacterial extracts containing microcystins (MCs) can be useful in determining their carcinogenic risk due to a genotoxic mechanism. An extract of cyanobacterial Microcystis ssp, containing MC-LR and -LA from a bloom collected in a eutrophic lake, showed genotoxicity to Oreochromis niloticus. DNA damage (comet assay) was significantly induced in peripheral erythrocytes with both tested concentrations of 6.90 μg kg(-1) bw and 13.80 μg kg(-1) bw through intraperitoneal injection (ip). There was no micronucleus induction after ip injection at concentrations of 6.90 μg kg(-1) bw and 13.80 μg kg(-1) bw. Body exposure resulted in micronucleus induction and DNA damage only at the highest tested concentrations of 103.72 μg L(-1). Thus, comet assay and ip injection revealed the highest levels of the genotoxicity of MCs. Apoptosis-necrosis test carried out at concentrations of 6.90 μg kg(-1) bw and 13.80 μg kg(-1) bw revealed that at low concentrations more apoptosis than necrosis occurred. At higher concentrations more necrosis than apoptosis occurred. PMID:21704053

  13. Decisions to regulate genotoxic substances

    International Nuclear Information System (INIS)

    Decisions to regulate genotoxic substances involve trade-offs between various incomparable factors such as risks to human health and other environmental risks, public perceptions, costs and uncertainties. Two different approaches towards these trade-offs are discussed. In one approach, all relevant factors are defined and trade-offs are considered using a general and very elaborate analysis. Cost-benefit analysis is an exponent of this approach. An illustration is given for the regulation of transboundary releases of radioactive materials. The other approach considers what is politically feasible for the time being and seeks a decision with much room for later corrections. Incrementalism is a philosophy in this vein. It is illustrated by reference to the regulation of transboundary air pollution. Weaknesses and strengths of the two approaches are discussed. (author)

  14. A pre-validation trial - testing genotoxicity of several chemicals using standard, medium- and high-throughput comet formats.

    Directory of Open Access Journals (Sweden)

    Kristine Bjerve Gutzkow

    2015-06-01

    Results obtained with the three systems (standard, medium- and high-throughput were essentially the same. The 96-minigel format was analysed with the fully automated scoring system IMSTAR and comparable results were achieved with the semi-automated scoring system from Perceptives. The known genotoxic chemicals MNU, B(aP, 4-NQO and cyclophosphamide showed little consistent sign of genotoxicity at concentrations causing limited cytotoxicity. D-mannitol and Triton X-100 were, as expected, non-genotoxic (though Triton X-100, at high concentrations, caused DNA breaks as an apparent secondary effect of cytotoxicity. Etoposide and bleomycin gave significant increase in DNA strand break at borderline cytotoxic concentrations. The limitation of the assay to detect damaged bases by known genotoxins may be overcome by incorporating a DNA repair enzyme, such as formamidopyrimidine-DNA-glycosylase (FPG, to convert damaged bases into breaks as shown by Azqueta A et al., Mutagenesis vol. 28 no. 3 pp. 271–277, 2013 .

  15. Ecotoxicity and genotoxicity of cadmium in different marine trophic levels.

    Science.gov (United States)

    Pavlaki, Maria D; Araújo, Mário J; Cardoso, Diogo N; Silva, Ana Rita R; Cruz, Andreia; Mendo, Sónia; Soares, Amadeu M V M; Calado, Ricardo; Loureiro, Susana

    2016-08-01

    Cadmium ecotoxicity and genotoxicity was assessed in three representative species of different trophic levels of marine ecosystems - the calanoid copepod Acartia tonsa, the decapod shrimp, Palaemon varians and the pleuronectiform fish Solea senegalensis. Ecotoxicity endpoints assessed in this study were adult survival, hatching success and larval development ratio (LDR) for A. tonsa, survival of the first larval stage (zoea I) and post-larvae of P. varians, egg and larvae survival, as well as the presence of malformations in the larval stage of S. senegalensis. In vivo genotoxicity was assessed on adult A. tonsa, the larval and postlarval stage of P. varians and newly hatched larvae of S. senegalensis using the comet assay. Results showed that the highest sensitivity to cadmium is displayed by A. tonsa, with the most sensitive endpoint being the LDR of nauplii to copepodites. Sole eggs displayed the highest tolerance to cadmium compared to the other endpoints evaluated for all tested species. Recorded cadmium toxicity was (by increasing order): S. senegalensis eggs < P. varians post-larvae < P. varians zoea I < S. senegalensis larvae < A. tonsa eggs < A. tonsa LDR. DNA damage to all species exposed to cadmium increased with increasing concentrations. Overall, understanding cadmium chemical speciation is paramount to reliably evaluate the effects of this metal in marine ecosystems. Cadmium is genotoxic to all three species tested and therefore may differentially impact individuals and populations of marine taxa. As A. tonsa was the most sensitive species and occupies a lower trophic level, it is likely that cadmium contamination may trigger bottom-up cascading effects in marine trophic interactions. PMID:27203468

  16. In vivo genotoxicity of nitramines, transformation products of amine-based carbon capture technology

    Directory of Open Access Journals (Sweden)

    Claire Coutris

    2015-05-01

    Full Text Available In times where we need to reduce our CO2 emissions to the atmosphere, it is important to get a clearer picture of the environmental impacts associated with potential mitigation technologies. Chemical absorption with amines is emerging as the most advanced mitigation technology for post-combustion capture of CO2 from fossil fuel power stations. Although the amine solvent used in this technology is recycled during the capture process, degradation products are formed and released into the environment. Among these degradation products, the aliphatic nitramine compounds dimethylnitramine and ethanolnitramine have been identified, whose environmental impact was unknown. In addition to conducting survival, growth and reproduction tests in a range of marine species, we looked into the in vivo genotoxic potential of these two compounds to experimentally exposed fish (Coutris et al. 2015. DNA damage was analyzed in blood samples collected from the caudal vein of juvenile turbot Scophthalmus maximus after 28 day exposure to nitramines, using the 12 mini-gels version of the comet assay, with and without digestion with formamidopyrimidine DNA glycosylase. Although whole organism bioassays indicated that nitramine toxicity through necrosis was low, the genotoxicity assessment revealed contrasting results, with ethanolnitramine found to be more genotoxic than dimethylnitramine by three orders of magnitude. At the lowest ethanolnitramine concentration (1 mg/L, 84 % DNA damage was observed, whereas 100 mg/L dimethylnitramine was required to cause 37 % DNA damage. The mechanisms of genotoxicity were also shown to differ between the two compounds, with oxidation of the DNA bases responsible for over 90 % of the genotoxicity of dimethylnitramine, whereas DNA strand breaks and alkali-labile sites were responsible for over 90 % of the genotoxicity of ethanolnitramine. Fish exposed to > 3 mg/L ethanolnitramine had virtually no DNA left in their red blood cells. The

  17. DNA damage and autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Rocha, Humberto; Garcia-Garcia, Aracely [Redox Biology Center and School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583 (United States); Panayiotidis, Mihalis I. [School of Community Health Sciences, University of Nevada, Reno, NV 89557 (United States); Franco, Rodrigo, E-mail: rfrancocruz2@unl.edu [Redox Biology Center and School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583 (United States)

    2011-06-03

    Both exogenous and endogenous agents are a threat to DNA integrity. Exogenous environmental agents such as ultraviolet (UV) and ionizing radiation, genotoxic chemicals and endogenous byproducts of metabolism including reactive oxygen species can cause alterations in DNA structure (DNA damage). Unrepaired DNA damage has been linked to a variety of human disorders including cancer and neurodegenerative disease. Thus, efficient mechanisms to detect DNA lesions, signal their presence and promote their repair have been evolved in cells. If DNA is effectively repaired, DNA damage response is inactivated and normal cell functioning resumes. In contrast, when DNA lesions cannot be removed, chronic DNA damage triggers specific cell responses such as cell death and senescence. Recently, DNA damage has been shown to induce autophagy, a cellular catabolic process that maintains a balance between synthesis, degradation, and recycling of cellular components. But the exact mechanisms by which DNA damage triggers autophagy are unclear. More importantly, the role of autophagy in the DNA damage response and cellular fate is unknown. In this review we analyze evidence that supports a role for autophagy as an integral part of the DNA damage response.

  18. SYNAPTONEMAL COMPLEX DAMAGE AS A MEASURE OF GENOTOXICITY AT MEIOSIS

    Science.gov (United States)

    Synaptonemal complex aberrations can provide a sensitive measure of chemical-specific alterations to meiotic chromosomes. Mitomycin C, cyclophosphamide, amsacrine, ellipticine, colchicine, vinblastine sulfate, and cis-platin exposures in mice have been shown to cause various patt...

  19. Genotoxicity studies in semiconductor industry. 1. In vitro mutagenicity and genotoxicity studies of waste samples resulting from plasma etching

    Energy Technology Data Exchange (ETDEWEB)

    Braun, R.; Huettner, E.M.; Merten, H.; Raabe, F. (Institute of Plant Genetics and Crop Plant Research, Gatersleben (Germany))

    1993-07-01

    Solid waste samples taken from the etching reactor, the turbo pump, and the waste air system of a plasma etching technology line in semiconductor production were studied as to their genotoxic properties in a bacterial repair test, in the Ames/Salmonella microsome assay, in the SOS chromotest, in primary mouse hepatocytes, and in Chinese hamster V79 cell cultures. All three waste samples were found to be active by inducing of unscheduled DNA-synthesis in mouse hepatocytes in vitro. In the bacterial rec-type repair test with Proteus mirabilis, waste samples taken from the turbo pump and the vacuum pipe system were not genotoxic. The waste sample taken from the chlorine-mediated plasma reactor was clearly positive in the bacterial repair assay and in the SOS chromotest with Escherichia coli. Mutagenic activity was demonstrated for all samples in the presence and absence of S9 mix made from mouse liver homogenate. Again, highest mutagenic activity was recorded for the waste sample taken from the plasma reactor, while samples collected from the turbo pump and from the waste air system before dilution and liberation of the air were less mutagenic. For all samples chromosomal damage in V79 cells was not detected, indicating absence of clastogenic activity in vitro. Altogether, these results indicate generation of genotoxic and mutagenic products as a consequence of chlorine-mediated plasma etching in the microelectronics industry and the presence of genotoxins even in places distant from the plasma reactor. Occupational exposure can be expected both from the precipitated wastes and from chemicals reaching the environment with the air stream.

  20. Mechanisms of 5-azacytidine (5AzC)-induced toxicity in the rat foetal brain

    Science.gov (United States)

    Ueno, Masaki; Katayama, Kei-Ichi; Nakayama, Hiroyuki; Doi, Kunio

    2002-01-01

    Mechanisms of 5-azacytidine (5AzC)-induced toxicity in the rat foetal brain were investigated. 5AzC (10 mg/kg) was injected into pregnant rats on day 13 of gestation and the protein and mRNA expressions of p53 and its transcriptional target genes, p21, bax, cyclin G1, fas, and gadd45, were examined in the foetal brain. The number of p53-positive cells peaked at 9 h after treatment (HAT) and those of apoptotic cells and p21-positive cells peaked at 12 HAT. The expressions of p21, bax, cyclin G1, and fas mRNAs were significantly elevated from 9 to 12 HAT. From the experiments using 5-bromo-2′-deoxyuridine (BrdU), as compared with controls, the migration of neuroepithelial cells significantly delayed and BrdU-positive signals were observed in many apoptotic cells from 9 to 24 HAT in the 5AzC-group. In addition, the number of S phase cells significantly decreased at 12 HAT. The present results indicate that 5AzC induced apoptosis and cell cycle arrest probably at G1 phase in the rat foetal brain and they might be mediated by p53 in response to DNA damage. PMID:12383193

  1. Genotoxicity biomarkers for monitoring occupational exposure to antineoplastic drugs

    Directory of Open Access Journals (Sweden)

    Hilda M. Rodríguez-Montero

    2016-06-01

    Full Text Available Context: The Institute of Oncology and Radiobiology (INOR is the leading institution for the diagnosis, treatment and follow-up of cancer in Cuba. The main methods used in cancer treatment are surgery, radiotherapy and chemotherapy. The last one involves the handling of hazardous substances, such as cytostatics, which implies a health risk to persons occupationally exposed to it. There are two sites where a considerable among of cytostatic is handled (Ambulatory Chemotherapy Room (ACR and the Central Unit of Cytostatic Mixture Preparation (CUCM. Genotoxicity biomarkers of exposure and effects have been widely used to detect occupational environment hazards. Aims: To evaluate genotoxicity biomarkers indicative of exposure and effects to cytostatics. Methods: In this study were tested samples taken from the surfaces of biological safety cabinets located in the Central Unit of Cytostatic Mixture using SOS – Chromotest. We also evaluated samples of oral mucosa exfoliated cells from exposed and control subjects, by micronucleus test. Results: All subjects were exposed and subjects who administered the mixes in the institution had an increased of DNA damage in comparison with the pharmaceutical staff that prepared it and wear the primary protection barriers properly. Conclusions: These results underline the efficiency of genotoxicological biomarkers in detecting the exposure levels and the deleterious effect of cytostatics on occupationally exposed personal.

  2. Comparative Genotoxicity of Cadmium and Lead in Earthworm Coelomocytes

    Directory of Open Access Journals (Sweden)

    Ptumporn Muangphra

    2011-01-01

    Full Text Available To determine genotoxicity to coelomocytes, Pheretima peguana earthworms were exposed in filter paper studies to cadmium (Cd and lead (Pb for 48 h, at concentrations less than the LC10—Cd: 0.09, 0.19, 0.38, 0.75, and 1.50 μg cm−2; Pb: 1.65, 3.29, 6.58, 13.16, and 26.32 μg cm−2. For Cd at 0.75 μg cm−2, in the micronucleus test (detects chromosomal aberrations, significant increases (<.05 in micronuclei and binucleate cells were observed, and in the comet assay (detects DNA single-strand breaks, tail DNA% was significantly increased. Lead was less toxic with minimal effects on DNA, but the binucleates were significantly increased by Pb at 3.29 μg cm−2. This study shows that Cd is more acutely toxic and sublethally genotoxic than Pb to P. peguana. Cadmium caused chromosomal aberrations and DNA single-strand breaks at 45% of the LC10 concentration. Lead, in contrast, did not induce DNA damage but caused cytokinesis defects.

  3. Genotoxic effects of bismuth (III oxide nanoparticles by comet assay

    Directory of Open Access Journals (Sweden)

    Reecep Liman

    2015-06-01

    Full Text Available Bismuth oxide is one of the important transition metal oxides and it has been intensively studied due to their peculiar characteristics (semiconductor band gap, high refractive index, high dielectric permittivity, high oxygen conductivity, resistivity, photoconductivity and photoluminescence etc.. Therefore, it is used such as microelectronics, sensor technology, optical coatings, transparent ceramic glass manufacturing, nanoenergetic gas generator, biosensor for DNA hybridization, potential immobilizing platforms for glucose oxidase and polyphenol oxidase, fuel cells, a additive in paints, an astringent in a variety of medical creams and topical ointments, and for the determination of heavy metal ions in drinking water, mineral water and urine. In addition this, Bismuth (III oxide nanoparticles (BONPs are favorable for the biomolecules adsorption than regular sized particles because of their greater advantages and novel characteristics (much higher specific surface, greater surface free energy, and good electrochemical stability etc.. Genotoxic effects of BONPs were investigated on the root cells of Allium cepa by Comet assay. A. cepa roots were treated with the aqueous dispersions of BONPs at 5 different concentrations (12.5, 25, 50, 75, and 100 ppm for 4 h. A significant increase in DNA damage was also observed at all concentrations of BONPs except 12.5 ppm by Comet assay. The results were also analyzed statistically by using SPSS for Windows; Duncan’s multiple range test was performed. These result indicate that BONPs exhibit genotoxic activity in A. cepa root meristematic cells.

  4. Argentine folk medicine: genotoxic effects of Chenopodiaceae family.

    Science.gov (United States)

    Gadano, A B; Gurni, A A; Carballo, M A

    2006-01-16

    Chenopodium ambrosioides L. and Chenopodium multifidum L. (Chenopodiaceae), common name: Paico, are medicinal plants. They are aromatic shrubs growing in South America. For centuries, they have been used due to its medicinal properties. However, there are few reports in literature about the genotoxic effects of these plants. There for, the aim of these work is the evaluation of genetic damage induced by decoction and infusion of this plants which were assayed in different concentrations (1, 10, 100, 1,000 microL extract/mL culture), by addition of the extract to human lymphocyte cell cultures, negative controls were included. The endpoints evaluated were chromosomal aberrations (CA), sister chromatid exchanges (SCE), cell proliferation kinetics (CPK) and mitotic index (MI). The repeated measure analysis of variance was used for statistic evaluation of the results. The results showed: (a) statistical increase in the percentage of cells with CA and in the frequency of SCE when cultures were exposed to both aromatic plants, (b) a decrease in MI of both Paicos assayed, although no modification in the CPK values was observed, (c) no effect was noticed in the analysis of Chenopodium album L., which was used as negative control of the essential oil. These results suggest a cyto and genotoxic effect of Chenopodium ambrosioides and Chenopodium multifidum aqueous extracts related to the essential oil of the plant (as Chenopodium album did not perform). PMID:16219440

  5. Argentine folk medicine: genotoxic effects of Chenopodiaceae family.

    Science.gov (United States)

    Gadano, A B; Gurni, A A; Carballo, M A

    2006-01-16

    Chenopodium ambrosioides L. and Chenopodium multifidum L. (Chenopodiaceae), common name: Paico, are medicinal plants. They are aromatic shrubs growing in South America. For centuries, they have been used due to its medicinal properties. However, there are few reports in literature about the genotoxic effects of these plants. There for, the aim of these work is the evaluation of genetic damage induced by decoction and infusion of this plants which were assayed in different concentrations (1, 10, 100, 1,000 microL extract/mL culture), by addition of the extract to human lymphocyte cell cultures, negative controls were included. The endpoints evaluated were chromosomal aberrations (CA), sister chromatid exchanges (SCE), cell proliferation kinetics (CPK) and mitotic index (MI). The repeated measure analysis of variance was used for statistic evaluation of the results. The results showed: (a) statistical increase in the percentage of cells with CA and in the frequency of SCE when cultures were exposed to both aromatic plants, (b) a decrease in MI of both Paicos assayed, although no modification in the CPK values was observed, (c) no effect was noticed in the analysis of Chenopodium album L., which was used as negative control of the essential oil. These results suggest a cyto and genotoxic effect of Chenopodium ambrosioides and Chenopodium multifidum aqueous extracts related to the essential oil of the plant (as Chenopodium album did not perform).

  6. The comet assay in testing the potential genotoxicity of nanomaterials

    Directory of Open Access Journals (Sweden)

    Amaya Azqueta

    2015-06-01

    validation. The comet assay has not been yet proposed as an appropriate test to check the genotoxic potential of NMs, though at a research level it is the most used in vitro assay and the second most used in vivo assay. Moreover, the combination of the comet assay with enzymes that convert altered bases to breaks allows the identification of DNA damage induced by secondary mechanisms (e.g. oxidative stress induced by inflammation, which is very relevant in the case of NMs. Possible problems with the use of the comet assay have been suggested: NMs have been detected in close association with comets, and might interact with the DNA; or NMs might inhibit the action of enzymes. However, control experiments have not confirmed that these interactions are significant.

  7. Effect of Green Tea Extract in Reducing Genotoxic Injuries of Cell Phone Microwaves on Bone Marrow

    OpenAIRE

    Zahra Zahedifar; Javad Baharara

    2013-01-01

    Background: Green tea (Camellia sinensis) extract is rich source of natural antioxidants specially catechin that is quickly absorbed into the body and it has cancer protective, anti microbial and anti inflammation effects. In this study has been studied role of green tea extract against genotoxic damage induced by cell phone microwaves on bone marrow polychromatic erythrocytes of adult male Balb/C mouse.Materials and Methods: In this experimental study 40 mouse were divided into five groups, ...

  8. Genotoxic differences by sex in nasal epithelium and blood leukocytes in subjects residing in a highly polluted area

    International Nuclear Information System (INIS)

    We describe differences by sex in genotoxic damage found in a population of medical students exposed to a highly oxidative atmosphere, compared with a control group, measured by the single-cell gel electrophoresis assay and histological changes in nasal epithelium smears. Cells were obtained from the nasal epithelium and blood leukocytes. Higher DNA damage in nasal cells and leukocytes was found in males compared to females and control subjects. The percentage of squamous metaplastic changes in the nasal epithelium was also higher in males compared with females and controls. The commutation of normal nasal epithelium by squamous cells might modify its protective function in the nose, increasing the risk of damage to the lower respiratory tract. Although, as medical students, males and females were exposed to the same environment and activity patterns, male genotoxicity damage was higher in control and exposed subjects. More research should be done in order to identify direct or indirect sexual hormone intervention

  9. Genotoxic Effect in Autoimmune Diseases Evaluated by the Micronucleus Test Assay: Our Experience and Literature Review

    Science.gov (United States)

    Torres-Bugarín, Olivia; Macriz Romero, Nicole; Ramos Ibarra, María Luisa; Flores-García, Aurelio; Valdez Aburto, Penélope; Zavala-Cerna, María Guadalupe

    2015-01-01

    Autoimmune diseases (AD) are classified into organ-specific, systemic, and mixed; all forms of AD share a high risk for cancer development. In AD a destructive immune response induced by autoreactive lymphocytes is started and continues with the production of autoantibodies against different targets; furthermore apoptosis failure and loss of balance in oxidative stress as a consequence of local or systemic inflammation are common features seen in AD as well. Micronucleus (MN) assay can be performed in order to evaluate loss of genetic material in a clear, accurate, fast, simple, and minimally invasive test. The MN formation in the cytoplasm of cells that have undergone proliferation is a consequence of DNA fragmentation during mitosis and the appearance of small additional nuclei during interphase. The MN test, widely accepted for in vitro and in vivo genotoxicity research, provides a sensitive marker of genomic damage associated to diverse conditions. In here, we present a review of our work and other published papers concerning genotoxic effect in AD, identified by means of the MN assay, with the aim of proposing this tool as a possible early biomarker for genotoxic damage, which is a consequence of disease progression. Additionally this biomarker could be used for follow-up, to asses genome damage associated to therapies. PMID:26339592

  10. Genotoxic Effect in Autoimmune Diseases Evaluated by the Micronucleus Test Assay: Our Experience and Literature Review

    Directory of Open Access Journals (Sweden)

    Olivia Torres-Bugarín

    2015-01-01

    Full Text Available Autoimmune diseases (AD are classified into organ-specific, systemic, and mixed; all forms of AD share a high risk for cancer development. In AD a destructive immune response induced by autoreactive lymphocytes is started and continues with the production of autoantibodies against different targets; furthermore apoptosis failure and loss of balance in oxidative stress as a consequence of local or systemic inflammation are common features seen in AD as well. Micronucleus (MN assay can be performed in order to evaluate loss of genetic material in a clear, accurate, fast, simple, and minimally invasive test. The MN formation in the cytoplasm of cells that have undergone proliferation is a consequence of DNA fragmentation during mitosis and the appearance of small additional nuclei during interphase. The MN test, widely accepted for in vitro and in vivo genotoxicity research, provides a sensitive marker of genomic damage associated to diverse conditions. In here, we present a review of our work and other published papers concerning genotoxic effect in AD, identified by means of the MN assay, with the aim of proposing this tool as a possible early biomarker for genotoxic damage, which is a consequence of disease progression. Additionally this biomarker could be used for follow-up, to asses genome damage associated to therapies.

  11. Genotoxic effect of Bothrops snake venoms and isolated toxins on human lymphocyte DNA.

    Science.gov (United States)

    Marcussi, Silvana; Stábeli, Rodrigo G; Santos-Filho, Norival A; Menaldo, Danilo L; Silva Pereira, Luciana L; Zuliani, Juliana P; Calderon, Leonardo A; da Silva, Saulo L; Antunes, Lusânia M Greggi; Soares, Andreimar M

    2013-04-01

    In the present study, micronucleus with cytokinesis blocking and comet assays were used to evaluate the genotoxic potential of Bothrops jararacussu, Bothrops atrox, Bothrops moojeni, Bothrops alternatus (Rhinocerophis alternatus) and Bothrops brazili snake venoms, and also of some isolated toxins (MjTX-I, BthTX-I and II myotoxins, BjussuMP-II metalloprotease, and BatxLAAO l-amino acid oxidase) on human lymphocytes. Significant DNA damages were observed, indicating genotoxic potential after exposure of the lymphocytes to the toxins BthTX-I, II and BatxLAAO compared to untreated and Cisplatin-treated controls, which were able to induce greater formation of micronuclei. B. brazili, B. jararacussu and B. atrox crude venoms also presented genotoxic potential, and the latter two induced DNA breakage 5 times more often than in normal environmental conditions (control without treatment). B. jararacussu venom and its isolated toxins, as well as an LAAO from B. atrox, were able to cause lymphocyte DNA breakage in the comet test with more than 85% damage levels. The DNA damage evaluation allows a widening of the toxic-pharmacological characterization of snake venoms and their toxins and also contributes to the understanding of the mechanisms of action of these molecules in several human pathologies. PMID:23333649

  12. Genotoxic potential of Cotinus coggygria Scop. (Anacardiaceae stem extract in vivo

    Directory of Open Access Journals (Sweden)

    Sanja Matic

    2011-01-01

    Full Text Available The intention was to evaluate the possible in vivo genotoxic potential in different cell-types, of a methanol extract obtained from the plant stem of Cotinus coggygria Scop., using the sex-linked recessive lethal (or SLRL test and alkaline comet assay. The SLRL test, revealed the genotoxic effect of this extract in postmeiotic and premeiotic germ-cell lines. The comet assay was carried out on rat liver and bone marrow at 24 and 72 h after intraperitoneal administration. For genotoxic evaluation, three concentrations of the extract were tested, viz., 500, 1000 and 2000 mg/kg body weight (bw, based on the solubility limit of the extract in saline. Comet tail moment and total scores in the group treated with 500 mg/kg bw, 24 and 72 h after treatment, were not significantly different from the control group, whereas in the groups of animals, under the same conditions, but with 1000 and 2000 mg/kg bw of the extract, scores were statistically so. A slight decrease in the comet score and tail moment observed in all the doses in the 72 h treatment, gave to understand that DNA damage induced by Cotinus coggygria extract decreased with time. The results of both tests revealed the genotoxic effect of Cotinus coggygria under our experimental conditions.

  13. Aporrectodea caliginosa, a suitable earthworm species for field based genotoxicity assessment?

    Energy Technology Data Exchange (ETDEWEB)

    Klobucar, Goeran I.V., E-mail: gklobuca@zg.biol.pmf.hr [Department of Zoology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10000 Zagreb (Croatia); Stambuk, Anamaria; Srut, Maja [Department of Zoology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10000 Zagreb (Croatia); Husnjak, Ivana [Ministry of Environmental Protection, Physical Planning and Construction, Ulica Republike Austrije 14, Zagreb (Croatia); Merkas, Martina [Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Salata 12, 10000 Zagreb (Croatia); Traven, Luka [Department of Environmental Medicine, Medical Faculty, University of Rijeka, Brace Branchetta 20a, 51000 Rijeka (Croatia); Teaching Institute of Public Health of the Primorsko-goranska County, Kresimirova 52a, 51000 Rijeka (Croatia); Cvetkovic, Zelimira [Department of Ecology, Institute of Public Health, Mirogojska c. 16, 10000 Zagreb (Croatia)

    2011-04-15

    There is a growing interest for the application of biomakers to field-collected earthworms. Therefore we have evaluated the usability of native populations of endogeic, widely distributed earthworm Aporrectodea caliginosa in the assessment of soil genotoxicity using the Comet assay. Validation of the Comet assay on earthworm coelomocytes has been established using commercially available Eisenia fetida exposed to copper, cadmium, and pentachlorophenol, along with A. caliginosa exposed to copper in a filter paper contact test. Neutral red retention time (NRRT) assay was conducted on copper exposed and field-collected earthworms. Significant DNA and lysosomal damage was measured using Comet and NRRT assays in native populations of A. caliginosa sampled from the polluted soils in the urban area in comparison to the earthworms from the reference site. The results of this study confirm the employment of A. caliginosa as a suitable species for the in situ soil toxicity and genotoxicity field surveys. - Research highlights: > Native A. caliginosa has shown significant biological effect measured by the Comet and NRRT assays. > The Comet assay on A. caliginosa and E. fetida has shown to be of similar sensitivity as the NRRT assay. > A. caliginosa is a suitable species for the in situ soil toxicity and genotoxicity field surveys. - Native populations of endogeic earthworm Aporrectodea caliginosa can be successfully applied in the genotoxicity field surveys using Comet assay.

  14. Immunocytotoxicity, cytogenotoxicity and genotoxicity of cadmium-based quantum dots in the marine mussel Mytilus galloprovincialis.

    Science.gov (United States)

    Rocha, Thiago Lopes; Gomes, Tânia; Cardoso, Cátia; Letendre, Julie; Pinheiro, José Paulo; Sousa, Vânia Serrão; Teixeira, Margarida Ribau; Bebianno, Maria João

    2014-10-01

    There is an increased use of Quantum Dot (QDs) in biological and biomedical applications, but little is known about their marine ecotoxicology. So, the aim of this study was to investigate the possible immunocytotoxic, cytogenotoxic and genotoxic effects of cadmium telluride QDs (CdTe QDs) on the marine mussel Mytilus galloprovincialis. Mussels were exposed to 10 μg L(-1) of CdTe QDs or to soluble Cd [Cd(NO3)2] for 14 days and Cd accumulation, immunocytotoxicity [hemocyte density, cell viability, lysosomal membrane stability (LMS), differential cell counts (DCC)], cytogenotoxicity (micronucleus test and nuclear abnormalities assay) and genotoxicity (comet assay) were analyzed. Results show that in vivo exposure to QDs, Cd is accumulated in mussel soft tissues and hemolymph and induce immunotoxic effects mediated by a decrease in LMS, changes in DCC, as well as genotoxicity (DNA damage). However, QDs do not induce significant changes in hemocytes density, cell viability and cytogenetic parameters in opposition to Cd(2+). Soluble Cd is the most cytotoxic and cytogenotoxic form on Mytilus hemocytes due to a higher accumulation of Cd in tissues. Results indicate that immunotoxicity and genotoxicity of CdTe QDs and Cd(2+) are mediated by different modes of action and show that Mytilus hemocytes are important targets for in vivo QDs toxicity.

  15. Investigation of genotoxic potential of various sizes Fe2O3 nanoparticles with comet assay

    Directory of Open Access Journals (Sweden)

    İbrahim Hakkı Ciğerci

    2015-06-01

    In this study, genotoxic potential of <50 nm and <100 nm Fe2O3 nanoparticles were investigated by using Comet Assay. Allium cepa root meristems were exposed with five doses (0.001, 0.01, 0.1, 1, 10 mM of <50 nm for 4 hour and three doses (2.5, 5 (EC50, 10 mM for <100 nm of Fe2O3 nanoparticle for 24 and 96 h. Methyl methanesulfonate -MMS (10 ppm was used as a positive control. The results were also analyzed statistically by using SPSS by Windows, 18.0. It was determined that different doses of <50 nm Fe2O3 nanoparticle have no genotoxic effect of DNA. Different doses of <100 nm Fe2O3 have no genotoxic but only 10 mM dose have genotoxic effect on DNA. When compared <50 nm with <100 nm of Fe2O3 nanoparticle; <50 nm have more effects than <100 nm of Fe2O3 on DNA damage.

  16. Gamma radiation at a human relevant low dose rate is genotoxic in mice

    Science.gov (United States)

    Graupner, Anne; Eide, Dag M.; Instanes, Christine; Andersen, Jill M.; Brede, Dag A.; Dertinger, Stephen D.; Lind, Ole C.; Brandt-Kjelsen, Anicke; Bjerke, Hans; Salbu, Brit; Oughton, Deborah; Brunborg, Gunnar; Olsen, Ann K.

    2016-09-01

    Even today, 70 years after Hiroshima and accidents like in Chernobyl and Fukushima, we still have limited knowledge about the health effects of low dose rate (LDR) radiation. Despite their human relevance after occupational and accidental exposure, only few animal studies on the genotoxic effects of chronic LDR radiation have been performed. Selenium (Se) is involved in oxidative stress defence, protecting DNA and other biomolecules from reactive oxygen species (ROS). It is hypothesised that Se deficiency, as it occurs in several parts of the world, may aggravate harmful effects of ROS-inducing stressors such as ionising radiation. We performed a study in the newly established LDR-facility Figaro on the combined effects of Se deprivation and LDR γ exposure in DNA repair knockout mice (Ogg1‑/‑) and control animals (Ogg1+/‑). Genotoxic effects were seen after continuous radiation (1.4 mGy/h) for 45 days. Chromosomal damage (micronucleus), phenotypic mutations (Pig-a gene mutation of RBCCD24‑) and DNA lesions (single strand breaks/alkali labile sites) were significantly increased in blood cells of irradiated animals, covering three types of genotoxic activity. This study demonstrates that chronic LDR γ radiation is genotoxic in an exposure scenario realistic for humans, supporting the hypothesis that even LDR γ radiation may induce cancer.

  17. Delineating the DNA damage response using systems biology approaches

    NARCIS (Netherlands)

    Stechow, Louise von

    2013-01-01

    Cellular responses to DNA damage are highly variable and strongly depend on the cellular and organismic context. Studying the DNA damage response is crucial for a better understanding of cancer formation and ageing as well as genotoxic stress-induced cancer therapy. To do justice to the multifaceted

  18. Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

    Institute of Scientific and Technical Information of China (English)

    Jaqueline Nascimento PICADA; Viviane Minuzzo PONTES; Patrícia PEREIRA; Bruna de Jesus Neto DOS SANTOS; Franciele CELSO; Jéssica Dias MONTEIRO; Kelly Morais DA ROSA; Leandro Rosa CAMACHO; Luciana Rodrigues VIEIRA; Taís Madelon FREITAS; Tatiana Grasiela DASILVA

    2011-01-01

    Aim:Aripiprazole is an antipsychotic agent to treat schizophrenia,which acts through dopamine D2 partial agonism,serotonin 5-HT1A partial agonism and 5-HT2A antagonism.This study was designed to evaluate the neurobehavioral effects and genotoxic/mutagenic activities of the agent,as well as its effects on lipoperoxidation.Methods:Open field and inhibitory avoidance tasks were used.Thirty min before performing the behavioral tasks,adult male CF-1 mice were administered aripiprazole (1,3 or 10 mg/kg,ip) once for the acute treatment,or the same doses for 5 d for the subchronic treatment.Genotoxic effects were assessed using comet assay in the blood and brain tissues.Mutagenic effects were evaluated using bone marrow micronucleus test.Lipoperoxidation was assessed with thiobarbituric acid reactive substances (TBARS).Results:Acute and subchronic treatments significantly decreased the number of crossing and rearing in the open field task.Acute treatment significantly increased the step-down latency for both the short- and long-term memory in the inhibitory avoidance task.Subchronic treatments with aripiprazole (3 and 10 mg/kg) caused significant DNA strain-break damage in peripheral blood but not in the brain.Mutagenic effect was not detected in the acute and subchronic treatments.Nor TBARS levels in the liver were affected.Conclusion:Aripiprazole improved memory,but could impair motor activities in mice.The drug increased DNA damage in blood,but did not show mutagenic effects,suggesting that it might affect long-term genomic stability.

  19. Genotoxic evaluation of polymeric nanoparticles

    Directory of Open Access Journals (Sweden)

    Tamara Iglesias Alonso

    2015-06-01

    Full Text Available An important strategy for optimizing the therapeutic efficacy of many conventional drugs is the development of polymeric nanoparticles (NPs, as it may expand their activities, reduce their toxicity, increase their bioactivity and improve biodistribution. The main objective of this study was to evaluate the genotoxicity of 8 different poly (anhydride NPs designed for the oral administration of therapeutic compounds by using the comet assay in combination with the enzyme formamidopypiridine DNA-glycosylase (FPG. Furthermore, the mitogen capacity of the NPs was evaluated by the proliferation assay. All NPs were tested at four concentrations (0, 0.5, 1 and 2 mg/mL in Caco-2 cells after 3 hours of treatment while selected NPs were also tested after 24 h. The comet assay was performed immediately after the treatment and cell proliferation was assessed by counting the treated cells after their incubation at 37 °C for 48h. Cells treated with 1 µM of the photosensitizer Ro 19-8022 plus 5 min of light, as well as cells treated with 100 µM H2O2 were included as positive controls in all the experiments. All NPs studied did not result in any increase in the frequency of strand breaks or alkali-labile sites in Caco-2 cells but they induced a slight concentration-dependent increase in net FPG sensitive sites (oxidized and/or alkylated bases. Furthermore, treated cells did not show changes in levels of proliferation in comparison with the negative control.

  20. Genotoxicity assessment of reactive and disperse textile dyes using human dermal equivalent (3D cell culture system).

    Science.gov (United States)

    Leme, Daniela Morais; Primo, Fernando Lucas; Gobo, Graciely Gomides; da Costa, Cleber Rafael Vieira; Tedesco, Antonio Claudio; de Oliveira, Danielle Palma

    2015-01-01

    Thousands of dyes are marketed daily for different purposes, including textile dyeing. However, there are several studies reporting attributing to dyes deleterious human effects such as DNA damage. Humans may be exposed to toxic dyes through either ingestion of contaminated waters or dermal contact with colored garments. With respect to dermal exposure, human skin equivalents are promising tools to assess in vitro genotoxicity of dermally applied chemicals using a three-dimensional (3D) model to mimic tissue behavior. This study investigated the sensitivity of an in-house human dermal equivalent (DE) for detecting genotoxicity of textile dyes. Two azo (reactive green 19 [RG19] and disperse red 1[DR1]) dyes and one anthraquinone (reactive blue 2 [RB2]) dye were analyzed. RG19 was genotoxic for DE in a dose-responsive manner, whereas RB2 and DR1 were nongenotoxic under the conditions tested. These findings are not in agreement with previous genotoxicological assessment of these dyes carried out using two-dimensional (2D) cell cultures, which showed that DR1 was genotoxic in human hepatoma cells (HepG2) and RG19 was nongenotoxic for normal human dermal fibroblasts (NHDF). These discrepant results probably may be due to differences between metabolic activities of each cell type (organ-specific genotoxicity, HepG2 and fibroblasts) and the test setup systems used in each study (fibroblasts cultured at 2D and three-dimensional [3D] culture systems). Genotoxicological assessment of textile dyes in context of organ-specific genotoxicity and using in vitro models that more closely resemble in vivo tissue architecture and physiology may provide more reliable estimates of genotoxic potential of these chemicals.

  1. Xylo-oligosaccharides and inulin affect genotoxicity and bacterial populations differently in a human colonic simulator challenged with soy protein

    DEFF Research Database (Denmark)

    Christophersen, C. T.; Petersen, Anne; Licht, Tine Rask;

    2013-01-01

    High dietary intakes of some protein sources, including soy protein, can increase colonic DNA damage in animals, whereas some carbohydrates attenuate this. We investigated whether inulin and xylo-oligosaccharides (XOS) could be protective against DNA strand breaks by adding them to a human colonic...... cornstarch for 10 day followed by soy protein with 1% XOS or 1% inulin for 10 day. Inulin did not alter genotoxicity but XOS significantly reduced PV genotoxicity and increased DV genotoxicity. Inulin and XOS significantly increased butyrate concentration in the DV but not PV. Numbers of the key butyrate......-producing bacterium Faecalibacterium prausnitzii were significantly increased in the PV and DV by inulin but significantly decreased by XOS in both vessels. Other bacteria examined were also significantly impacted by the carbohydrate treatments or by the vessel (i.e., pH). There was a significant overall inverse...

  2. p53 Promoter-based Reporter Gene in vitro Assays for Quick Assessment of Agents with Genotoxic Potential

    Institute of Scientific and Technical Information of China (English)

    Huaixing LI; Ke SHI; Ruiwen CHEN; Yan HE; Dan WU; Shuhan SUN

    2007-01-01

    The p53 promoter-based green fluorescent protein (GFP) and luciferase reporter gene assays have been established for detecting DNA damage induced by genotoxic agents.To evaluate the system,NIH3T3 cells transfected with either pHP53-GFP or pMP53-GFP construct were treated with mitomycin or 5-fluorouracil.Expression of the GFP reporter gene was significantly and specifically induced in the cells exposed to mitomycin or 5-fluorouracil.Then we treated NIH3T3 cells harboring pHP53-Luc or pMP53-Luc vector with mitomycin,5-fluorouracil or cisplatin at various concentrations.Similarly,exposure of the cells to these agents with genotoxic potentials resulted in a dose-dependent induction in luciferase reporter gene expression.Thus,these in vitro reporter gene assays could provide an ideal system for quick assessment or screening of agents with genotoxic potential.

  3. Genotoxic and mutagenic effects of vigabatrin, a γ-aminobutyric acid transaminase inhibitor, in Wistar rats submitted to rotarod task.

    Science.gov (United States)

    Coelho, V R; Sousa, K; Pires, T R; Papke, Dkm; Vieira, C G; de Souza, L P; Leal, M B; Schunck, Rva; Picada, J N; Pereira, P

    2016-09-01

    Vigabatrin (VGB) is an antiepileptic drug thatincreases brain γ-aminobutyric acid (GABA) levels through irreversible inhibition of GABA transaminase. The aim of this study was to evaluate neurotoxicological effects of VGB measuring motor activity and genotoxic and mutagenic effects after a single and repeated administration. Male Wistar rats received saline, VGB 50, 100, or 250 mg/kg by gavage for acute and subchronic (14 days) treatments and evaluated in the rotarod task. Genotoxicity was evaluated using the alkaline version of the comet assay in samples of blood, liver, hippocampus, and brain cortex after both treatments. Mutagenicity was evaluated using the micronucleus test in bone marrow of the same animals that received subchronic treatment. The groups treated with VGB showed similar performance in rotarod compared with the saline group. Regarding the acute treatment, it was observed that only higher VGB doses induced DNA damage in blood and hippocampus. After the subchronic treatment, VGB did not show genotoxic or mutagenic effects. In brief, VGB did not impair motor activities in rats after acute and subchronic treatments. It showed a repairable genotoxic potential in the central nervous system since genotoxicity was observed in the acute treatment group. PMID:26500220

  4. Baccharis trimera (Less.) DC as genotoxicity indicator of exposure to coal and emissions from a thermal power plant.

    Science.gov (United States)

    Menezes, Ana Paula Simões; Da Silva, Juliana; Roloff, Joice; Reyes, Juliana; Debastiani, Rafaela; Dias, Johnny F; Rohr, Paula; de Barros Falcão Ferraz, Alexandre

    2013-10-01

    During coal combustion, hazardous elements are discharged that impair environmental quality. Plant cover is the first available surface for the atmospheric pollutants in terrestrial ecosystems. The aim of this study was to evaluate genotoxicity in the aqueous extract of the native plant, Baccharis trimera, exposed to coal and emissions from a thermal power plant (coal-fired power plant in Candiota, Brazil), correlating seasonality, wind tunnel predominance, and presence of inorganic elements. The presence of inorganic elements in the aerial parts of B. trimera was analyzed by particle-induced X-ray emission (PIXE) spectrometry, and genotoxicity was evaluated by ex vivo comet assay. The genotoxic effects of aqueous extracts of B. trimera from four sites located in the area around power plant were analyzed by comet assay in peripheral human lymphocytes. Winter samples showed greater levels of metals than summer samples. Genotoxicity was detected in B. trimera extracts collected from the region exposed to extraction and burning coal. Extracts from the site impacted by the dominant wind induced more damage to DNA than those from other sites. Based on our data, we can suggest that in winter the inorganic elements from extraction and burning of coal and carried through the wind tunnel were responsible for the genotoxicity observed in aqueous extract of B. trimera.

  5. Genotoxicity of citrus wastewater in prokaryotic and eukaryotic cells and efficiency of heterogeneous photocatalysis by TiO(2).

    Science.gov (United States)

    Saverini, Marghereth; Catanzaro, Irene; Sciandrello, Giulia; Avellone, Giuseppe; Indelicato, Sergio; Marcì, Giuseppe; Palmisano, Leonardo

    2012-03-01

    The presence of (±)α-pinene, (+)β-pinene, (+)3-carene, and R-(+)limonene terpenes in wastewater of a citrus transformation factory was detected and analyzed, in a previous study, by using Solid Phase Micro-extraction (SPME) followed by GC analyses. Purpose of that research was to compare the genotoxic responses of mixtures of terpenes with the genotoxicity of the individual compounds, and the biological effects of actual wastewater. Genotoxicity was evaluated in the Salmonella reversion assay (Ames test) and in V79 cells by Comet assay. Ames tests indicated that the four single terpenes did not induce an increase of revertants frequency. On the contrary, the mixtures of terpenes caused, in the presence of metabolic activation, a highly significant increase of the revertants in TA100 strain in comparison to the control. The Comet assay showed a significant increase in DNA damage in V79 cells treated for 1h with single or mixed terpenes. Moreover, the actual wastewater was found highly genotoxic in bacterial and mammalian cells. Photocatalytic tests completely photodegraded the pollutants present in aqueous wastewater and the initial high genotoxicity of samples of wastewater collected during the photocatalytic run, was completely lose in 3h of irradiation.

  6. Genotoxic and immunotoxic potential effects of selected psychotropic drugs and antibiotics on blue mussel (Mytilus edulis) hemocytes

    International Nuclear Information System (INIS)

    The potential toxicity of pharmaceuticals towards aquatic invertebrates is still poorly understood and sometimes controversial. This study aims to document the in vitro genotoxicity and immunotoxicity of psychotropic drugs and antibiotics on Mytilus edulis. Mussel hemocytes were exposed to fluoxetine, paroxetine, venlafaxine, carbamazepine, sulfamethoxazole, trimethoprim and erythromycin, at concentrations ranging from μg/L to mg/L. Paroxetine at 1.5 μg/L led to DNA damage while the same concentration of venlafaxine caused immunomodulation. Fluoxetine exposure resulted in genotoxicity, immunotoxicity and cytotoxicity. In the case of antibiotics, trimethoprim was genotoxic at 200 μg/L and immunotoxic at 20 mg/L whereas erythromycin elicited same detrimental effects at higher concentrations. DNA metabolism seems to be a highly sensitive target for psychotropic drugs and antibiotics. Furthermore, these compounds affect the immune system of bivalves, with varying intensity. This attests the relevance of these endpoints to assess the toxic mode of action of pharmaceuticals in the aquatic environment. - Highlights: • Psychotropic drugs and antibiotics affect the immune system of Mytilus edulis. • Genotoxic and immunotoxic endpoints were relevant to assess pharmaceuticals toxicity. • DNA metabolism is a highly sensitive target for pharmaceuticals. • Fluoxetine and paroxetine were the most toxic compounds on mussel hemocytes. - Psychotropic drugs and antibiotics have the potential to cause immune toxicity and genotoxicity on Mytilus edulis hemocytes

  7. Deoxynivalenol induces cytotoxicity and genotoxicity in animal primary cell culture.

    Science.gov (United States)

    Singh, Shweta; Banerjee, Subham; Chattopadhyay, Pronobesh; Borthakur, Sashin Kumar; Veer, Vijay

    2015-03-01

    Deoxynivalenol (DON), a mycotoxin produced by Fusarium graminearum, is widely found as a contaminant of food. DON is responsible for a wide range of toxic activities, including gastro-intestinal, lymphoid, bone-marrow and cardiotoxicity. But, the complete explorations of toxicity in terms of hepatotoxicity, nephrotoxicity, cytotoxicity and genotoxicity as well have not been documented well. Again, the mechanisms through which DON damages the DNA and promotes cellular toxicity are not well established. Considering the above fact, this research article is focused on the effects of DON-induced toxicities on experimental animal model as well as its effects on cellular level via various toxicological investigations. DON treatment showed cytotoxicity and DNA damage. Further, flow cytometric analysis of hepatocytes showed cellular apoptosis, suggesting that DON-induced hepatotoxicity is, may be partly, mediated by apoptosis. Moreover, significant differences were found in each haematology and clinical chemistry value, either (p > 0.05). No abnormality of any organ was found during histopathological examination. Hence, it can be concluded that DON induces oxidative DNA damage and increases the formation of centromere positive micronuclei due to aneugenic activity. PMID:25578892

  8. Genotoxicity assessment of intravenously injected titanium dioxide nanoparticles in gpt delta transgenic mice.

    Science.gov (United States)

    Suzuki, Tetsuya; Miura, Nobuhiko; Hojo, Rieko; Yanagiba, Yukie; Suda, Megumi; Hasegawa, Tatsuya; Miyagawa, Muneyuki; Wang, Rui-Sheng

    2016-05-01

    Titanium dioxide (TiO2) nanoparticles are increasingly manufactured in large amounts for use in industrial applications such as cosmetics, pigments, foods, and as photo-catalysts. Many in vitro studies have examined the genotoxicity of TiO2 nanomaterials; some of these studies suggest that TiO2 nanoparticles (NPs) are genotoxic. Several in vivo studies have also been reported recently, but the results are inconsistent. In this study, we investigated, using several genotoxicity endpoints, the effects of dispersed TiO2 suspensions following multiple intravenous injections in mice. Male gpt Delta C57BL/6J mice were administered TiO2 NPs at doses of 2, 10 or 50mg/kg body weight per week for 4 consecutive weeks. Genotoxic effects were then analyzed by the Pig-a gene mutation assay and the micronucleus assay on peripheral blood, and by the alkaline comet, gpt mutation, and Spi(-) mutation assays on the liver. We also assessed the localization of TiO2 NPs in the liver, by transmission electron microscopy. Administration of TiO2 NPs did not significantly increase any of the following endpoints: frequency of Pig-a mutants (erythrocytes); frequency of micronuclei (reticulocytes); level of DNA damage (liver); frequencies of gpt and Spi(-) mutants (liver). Most TiO2 NPs in the liver were found in the sinuses and inside Kupffer cells, although some were occasionally observed in liver parenchymal cells. These results indicate that TiO2 NPs do not have genotoxic effects on mouse liver or bone marrow.

  9. Genotoxic effect of ethacrynic acid and impact of antioxidants

    Energy Technology Data Exchange (ETDEWEB)

    Ward, William M.; Hoffman, Jared D.; Loo, George, E-mail: g_loo@uncg.edu

    2015-07-01

    It is known that ethacrynic acid (EA) decreases the intracellular levels of glutathione. Whether the anticipated oxidative stress affects the structural integrity of DNA is unknown. Therefore, DNA damage was assessed in EA-treated HCT116 cells, and the impact of several antioxidants was also determined. EA caused both concentration-dependent and time-dependent DNA damage that eventually resulted in cell death. Unexpectedly, the DNA damage caused by EA was intensified by either ascorbic acid or trolox. In contrast, EA-induced DNA damage was reduced by N-acetylcysteine and by the iron chelator, deferoxamine. In elucidating the DNA damage, it was determined that EA increased the production of reactive oxygen species, which was inhibited by N-acetylcysteine and deferoxamine but not by ascorbic acid and trolox. Also, EA decreased glutathione levels, which were inhibited by N-acetylcysteine. But, ascorbic acid, trolox, and deferoxamine neither inhibited nor enhanced the capacity of EA to decrease glutathione. Interestingly, the glutathione synthesis inhibitor, buthionine sulfoxime, lowered glutathione to a similar degree as EA, but no noticeable DNA damage was found. Nevertheless, buthionine sulfoxime potentiated the glutathione-lowering effect of EA and intensified the DNA damage caused by EA. Additionally, in examining redox-sensitive stress gene expression, it was found that EA increased HO-1, GADD153, and p21mRNA expression, in association with increased nuclear localization of Nrf-2 and p53 proteins. In contrast to ascorbic acid, trolox, and deferoxamine, N-acetylcysteine suppressed the EA-induced upregulation of GADD153, although not of HO-1. Overall, it is concluded that EA has genotoxic properties that can be amplified by certain antioxidants. - Highlights: • Ethacrynic acid (EA) caused cellular DNA damage. • EA-induced DNA damage was potentiated by ascorbic acid or trolox. • EA increased ROS production, not inhibited by ascorbic acid or trolox. • EA

  10. In vivo genotoxic effects of industrial waste leachates in mice following oral exposure.

    Science.gov (United States)

    Chandra, Saurabh; Chauhan, Lalit K S; Dhawan, Alok; Murthy, Ramesh C; Gupta, Shrawan K

    2006-06-01

    Contamination of ground water by industrial waste poses potential health hazards for man and his environment. The improper disposal of toxic wastes could allow genotoxic chemicals to percolate into ground waters, and these contaminated ground waters may produce toxicity, including mutation and eventually cancer, in exposed individuals. In the present study, we evaluated the in vivo genotoxic potential of leachates made from three different kinds of industrial waste (tannery waste, metal-based waste, and waste containing dyes and pigments) that are disposed of in areas adjoining human habitation. Three different doses of test leachates were administered by oral gavage for 15 consecutive days to Swiss albino mice; their bone marrow cells were examined for chromosome aberrations (CAs), micronucleated polychromatic erythrocytes (MNPCEs), and DNA damage using the alkaline Comet assay. Exposure to the leachates resulted in significant (P dye-waste leachate produced weaker genotoxic responses. The cytogenetic abnormalities and DNA damage produced by the leachates indicate that humans consuming water contaminated with these materials are at increased risk of developing adverse health consequences.

  11. Genotoxicity and cytotoxicity of cisplatin treatment combined with anaesthetics on EAT cells in vivo.

    Science.gov (United States)

    Brozovic, Gordana; Orsolic, Nada; Knezevic, Fabijan; Horvat Knezevic, Anica; Benkovic, Vesna; Sakic, Katarina; Hrgovic, Zlatko; Bendelja, Kreso; Fassbender, Walter J

    2009-06-01

    In this study, DNA damage in tumour cells, as well as irreversible cell damage leading to apoptosis induced in vivo by the combined application of cisplatin and inhalation anaesthetics, was investigated. The genotoxicity of anaesthetics on Ehrlich ascites tumour (EAT) cells of mice, alone or in combined application with cisplatin, was estimated by using the alkaline comet assay. The percentage of EAT cell apoptosis was quantified by flow cytometry. Groups of EAT-bearing mice were (i) treated intraperitoneally with cisplatin, (ii) exposed to repeated anaesthesia with inhalation anaesthetic, and (iii) subjected to combined treatment of exposure to anaesthetics after cisplatin for 3 days. Sevoflurane, halothane and isoflurane caused strong genotoxic effects on tumour cells in vivo. The tested anaesthetics alone showed no direct effect on programmed cell death although sevoflurane and especially halothane decreased the number of living EAT cells in peritoneal cavity lavage. Repeated anaesthesia with isoflurane had stimulatory effects on EAT cell proliferation and inhibited tumour cell apoptosis (6.11%), compared to the control group (10.26%). Cisplatin caused massive apoptosis of EAT cells (41.14%) and decreased the number of living EAT cells in the peritoneal cavity. Combined cisplatin and isoflurane treatment additionally increased EAT cell apoptosis to 51.32%. Combined treatment of mice with cisplatin and all anaesthetics increased the number of living tumour cells in the peritoneal cavity compared to cisplatin treatment of mice alone. These results suggest that the inhalation of anaesthetics may protect tumour cells from the cisplatin-induced genotoxic and cytotoxic effects.

  12. Investigating the embryo/larval toxic and genotoxic effects of {gamma} irradiation on zebrafish eggs

    Energy Technology Data Exchange (ETDEWEB)

    Simon, O., E-mail: olivier.simon@irsn.fr [Laboratoire de Radioecologie et d' Ecotoxicologie, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat 186, BP3, 13115 Saint-Paul-lez-Durance Cedex (France); Massarin, S. [Laboratoire de Modelisation Environnementale, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat 159, BP3, 13115 Saint-Paul-lez-Durance Cedex (France); Coppin, F. [Laboratoire de Radioecologie et d' Ecotoxicologie, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat 186, BP3, 13115 Saint-Paul-lez-Durance Cedex (France); Hinton, T.G. [Service d' Etude du Comportement des Radionucleides dans les Ecosystemes, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat 159, BP3, 13115 Saint-Paul-lez-Durance Cedex (France); Gilbin, R. [Laboratoire de Radioecologie et d' Ecotoxicologie, Institut de Radioprotection et de Surete Nucleaire, Cadarache, Bat 186, BP3, 13115 Saint-Paul-lez-Durance Cedex (France)

    2011-11-15

    Eggs/larval of freshwater fish (Danio rerio) were exposed to low dose rates of external gamma radiation (from 1 to 1000 mGy d{sup -1}) over a 20-day period, with the objective of testing the appropriateness of the 10 mGy d{sup -1} guideline suggested by the IAEA. The present study examines different endpoints, mortality and hatching time and success of embryos as well as the genotoxicity of {gamma}-irradiations (after 48 h). The 20-day embryo-larval bioassay showed an enhanced larval resistance to starvation after chronic exposure to {gamma} irradiation (from low 1 mGy d{sup -1} to high dose rate 1000 mGy d{sup -1}) and an acceleration in hatching time. Gamma irradiation led to increased genotoxic damage Ito zebrafish egg (40-50% DNA in tail in Comet assay) from the lowest dose rate (1 mGy d{sup -1}). Possible mechanisms of {gamma} radiotoxicity and implications for radioprotection are discussed. - Highlights: > Relevant information on the {gamma} radiation impact on early life stage biota is scarce. > The eggs of zebrafish Danio rerio were selected as biological model. > We test the appropriateness of the 10 mGy d{sup -1} guideline (IAEA). > We observed effects measured at individual levels (starvation, hatching time). > Chronic gamma irradiation led to increased genotoxic damage to zebrafish egg. > {gamma} radiotoxicity mechanisms and implications for radioprotection are discussed.

  13. Genotoxic Effects of PAH Containing Sludge Extracts in Chinese Hamster Ovary Cell Cultures

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective Many studies have been conducted in order to evaluate the genotoxicity of chemicals and waste materials, which utilized in vivo test protocols. The use of animals for routine toxicity testing is now questioned by a growing segment of society[1]. Methods Keeping the above fact in mind, we have conducted in the present study the genotoxicity evaluation of oily sludge samples generated from a petroleum refinery and petrochemical industry and ETP sludge from petroleum refinery using DNA damage, chromosomal aberration, p53 protein induction and apoptosis in short term in vitro mammalian Chinese Hamster Ovary cell cultures. Results It is evident from the results that the oily sludge compounds derived from petroleum refinery and petrochemical industry could cause DNA damage, chromosomal aberration, p53 protein accumulation and apoptotic cell death on exposure to oily sludge extracts in the presence of metabolic activation system (S-9 mix), however, ETP sludge extract could not cause significant genotoxicity in comparison to oily sludge extract and negative control. Conclusion The effect may be attributed to polycyclic aromatic hydrocarbons present in the samples as evidenced from GC-MS.

  14. Protective effect of bixin on cisplatin-induced genotoxicity in PC12 cells.

    Science.gov (United States)

    Dos Santos, Graciela Cristina; Mendonça, Leonardo Meneghin; Antonucci, Gilmara Ausech; Dos Santos, Antonio Cardozo; Antunes, Lusânia Maria Greggi; Bianchi, Maria de Lourdes Pires

    2012-02-01

    Bixin is the main carotenoid found in annatto seeds (Bixa orellana L.) and is responsible for their reddish-orange color. The antioxidant properties of this compound are associated with its ability to scavenge free radicals, which may reduce damage and protect tissues against toxicity caused by anticancer drugs such as cisplatin. In this study, the genotoxicity and antigenotoxicity of bixin on cisplatin-induced toxicity in PC12 cells was assessed. Cytotoxicity was evaluated using the MTT assay, mutagenicity, genotoxicity, and protective effect of bixin were evaluated using the micronucleus test and comet assay. PC12 cells were treated with bixin (0.05, 0.08, and 0.10μg/mL), cisplatin (0.1μg/mL) or a combination of both bixin and cisplatin. Bixin was neither cytotoxic nor genotoxic compared to the controls. In the combined treatment bixin significantly reduced the percentage of DNA in tail and the frequency of micronuclei induced by cisplatin. This result suggests that bixin can function as a protective agent, reducing cisplatin-induced DNA damage in PC12 cells, and it is possible that this protection could also extend to neuronal cells. Further studies are being conducted to better understand the mechanisms involved in the activity of this protective agent prior to using it therapeutically. PMID:22019694

  15. Protective role of Lactobacillus plantarum A7 against irinotecan-induced genotoxicity

    Directory of Open Access Journals (Sweden)

    Soheila Sepahi

    2016-04-01

    Full Text Available Objective: Irinotecan is a botanical derivative and an anti-cancer drug with cytotoxic and genotoxic effects. The present study evaluated the effect of Lactobacillus plantarum A7 on the genotoxic activity of irinotecan in a hepatocellular carcinoma cell line (HepG2 by comet assay. Materials and Methods: HepG2 were incubated with irinotecan (100 µM, heat-killed cells (0.025 µg/ml + irinotecan (100 µM, and cell-free supernatants (0.5 and 1 µg/ml of L. plantarum A7 + irinotecan (100 µM. Phosphate buffered saline (PBS was used as negative control. Results: Irinotecan was shown to induce DNA damage in HepG2 cells. The results showed that heat-killed cells (0.025 µg/ml and cell-free supernatants (0.5 and 1 µg/ml of L. plantarum significantly reduce irinotecan- induced DNA damage. Conclusion: Our results indicate that L. plantarum A7 can decrease the genotoxic effects of irinotecan in HepG2 cells, in vitro. This finding may be supportive for the optimization of therapeutic efficacy in irinotecan treatment.

  16. Grape seed extract prevents gentamicin-induced nephrotoxicity and genotoxicity in bone marrow cells of mice.

    Science.gov (United States)

    El-Ashmawy, Ibrahim M; El-Nahas, Abeer F; Salama, Osama M

    2006-09-01

    The protection conferred by grape seed extract against gentamicin-induced nephrotoxicity and bone marrow chromosomal aberrations have been evaluated in adult Swiss albino mice. The activity of reduced glutathione peroxidase (GSH peroxidase), the levels of glutathione (GSH) and lipid peroxidation as malondialdehyde (MDA) in the kidneys homogenates, serum urea and creatinine were measured, and in addition the changes in kidney histology and bone marrow chromosomes were investigated. Gentamicin (80 mg/kg b.wt. intraperitoneally for 2 weeks) induced kidney damage as indicated from a pronounced changes in kidney histology, a significant increase in serum urea and creatinine and MDA content in the kidney homogenate. While the activity of the antioxidant enzyme GSH peroxidase and the level of GSH were significantly decreased. Gentamicin induced genotoxicity indicated by increased the number of aberrant cells and different types of structural chromosomal aberrations (fragment, deletion and ring chromosome) and showed no effect on mitotic activity of the cell. Pretreatment with grape seed extract (7 days) and simultaneously (14 days) with gentamicin significantly protected the kidney tissue by ameliorating its antioxidant activity. Moreover, grape seed extract significantly protected bone marrow chromosomes from gentamicin induced genotoxicity by reducing the total number of aberrant cells, and different types of structural chromosomal aberrations. It could be concluded that grape seed extract acts as a potent antioxidant prevented kidney damage and genotoxicity of bone marrow cells.

  17. Genotoxic potential of BM-21, an aqueous-ethanolic extract from Thalassia testudinum marine plant.

    Directory of Open Access Journals (Sweden)

    Yadira Ansoar

    2014-12-01

    Full Text Available Context: BM-21 is a hydro-ethanolic extract obtained from the leaves of Thalassia testudinum marine plant, which is rich in polyphenols, and it has demonstrated antioxidant, anti-inflammatory, cytoprotective and neuroprotective properties. Aims: To investigate the genotoxicity potential of BM-21. Methods: Salmonella typhimurium Hist. – strains were used in the pointmutation test and Escherichia coli cells were used in SOS response test. DNA primary damage was tested in hepatocytes of mice treated with oral dose of the extract (2000 mg/kg. Bone marrow micronucleus assay was used in mice to detect clastogenic damage while serum from the same animals was used to determine MDA levels in order to find out the influence of BM-21 on lipid peroxidation. Positive and negative controls were included in all experimental series. Results: BM-21 did not increase the frequency of reverse mutations in the Ames test, and it did not induce primary damage in E. coli. Comet assay showed that 2 000 mg/kg of BM-21 induced single strand breaks or alkali-labile sites in the hepatocytes from the treated mice. However, no increase in the micronucleus frequency was observed in mice polychromatic erythrocytes and significantly reduced MDA levels were detected. Conclusions: BM-21 was neither mutagenic nor induces DNA damage to prokaryotic cells. Although, it increased DNA strand breaks in vivo, this one was not translated into clastogenic damage to the whole organism. Results suggested that BM-21 was not mutagenic or genotoxic under our experimental conditions.

  18. Acute effects of a prooxidant herbicide on the microalga Chlamydomonas reinhardtii: Screening cytotoxicity and genotoxicity endpoints

    International Nuclear Information System (INIS)

    Highlights: • Mitochondrial membrane potential constituted the most sensitive parameter assayed. • Several genotoxicity methods were applied for first time in ecotoxicological studies. • Oxidative DNA base damage (8-OHdG) was induced by paraquat exposure. • Cells with DNA strand breakage and subG1-nuclei increased in treated cultures. • Typical apoptosis hallmarks were observed in microalgal cells exposed to paraquat. - Abstract: Since recent evidence has demonstrated that many types of chemicals exhibit oxidative and/or genotoxic potential on living organisms, reactive oxygen species (ROS) formation and DNA damage are currently the best accepted paradigms to assess the potential hazardous biological effects of a wide range of contaminants. The goal of this study was to evaluate the sensitivity of different cytotoxicity and genotoxicity responses on the model microalga Chlamydomonas reinhardtii exposed to the prooxidant herbicide paraquat. In addition to the growth endpoint, cell viability, mitochondrial membrane potential and presence of reactive oxygen species (ROS) were assayed as potential markers of cytotoxicity using flow cytometry (FCM). To study the effects of paraquat on C. reinhardtii DNA, several genotoxicity approaches were implemented for the first time in an ecotoxicological study on microalgae. Oxidative DNA base damage was analysed by measuring the oxidative DNA lesion 8-OHdG by FCM. DNA fragmentation was analysed by different methods: comet assay, and cell cycle analysis by FCM, with a particular focus on the presence of subG1-nuclei. Finally, effects on morphology of nuclei were monitored through DAPI staining. The evaluation of these endpoints showed that several physiological and biochemical parameters reacted to oxidative stress disturbances with greater sensitivity than integrative parameters such as growth rates or cell viability. The experiments revealed concentration-dependent cytotoxicity (ROS formation, depolarization of

  19. Acute effects of a prooxidant herbicide on the microalga Chlamydomonas reinhardtii: Screening cytotoxicity and genotoxicity endpoints

    Energy Technology Data Exchange (ETDEWEB)

    Esperanza, Marta; Cid, Ángeles; Herrero, Concepción; Rioboo, Carmen, E-mail: carmen.rioboo@udc.es

    2015-08-15

    Highlights: • Mitochondrial membrane potential constituted the most sensitive parameter assayed. • Several genotoxicity methods were applied for first time in ecotoxicological studies. • Oxidative DNA base damage (8-OHdG) was induced by paraquat exposure. • Cells with DNA strand breakage and subG1-nuclei increased in treated cultures. • Typical apoptosis hallmarks were observed in microalgal cells exposed to paraquat. - Abstract: Since recent evidence has demonstrated that many types of chemicals exhibit oxidative and/or genotoxic potential on living organisms, reactive oxygen species (ROS) formation and DNA damage are currently the best accepted paradigms to assess the potential hazardous biological effects of a wide range of contaminants. The goal of this study was to evaluate the sensitivity of different cytotoxicity and genotoxicity responses on the model microalga Chlamydomonas reinhardtii exposed to the prooxidant herbicide paraquat. In addition to the growth endpoint, cell viability, mitochondrial membrane potential and presence of reactive oxygen species (ROS) were assayed as potential markers of cytotoxicity using flow cytometry (FCM). To study the effects of paraquat on C. reinhardtii DNA, several genotoxicity approaches were implemented for the first time in an ecotoxicological study on microalgae. Oxidative DNA base damage was analysed by measuring the oxidative DNA lesion 8-OHdG by FCM. DNA fragmentation was analysed by different methods: comet assay, and cell cycle analysis by FCM, with a particular focus on the presence of subG1-nuclei. Finally, effects on morphology of nuclei were monitored through DAPI staining. The evaluation of these endpoints showed that several physiological and biochemical parameters reacted to oxidative stress disturbances with greater sensitivity than integrative parameters such as growth rates or cell viability. The experiments revealed concentration-dependent cytotoxicity (ROS formation, depolarization of

  20. Evaluation of the genotoxic and mutagenic potentials of phytotherapic and homeopathic solutions of Euphorbia tirucalli Lineu (Aveloz

    Directory of Open Access Journals (Sweden)

    Carla Holandino

    2011-07-01

    Full Text Available Introduction: Euphorbia tirucalli Lineu, commonly known as Aveloz, is a very common plant found in tropical regions [1]. The ingestion or contact with its latex causes symptoms such as vomiting and diarrhea, pallor, skin irritation, hepatotoxicity as well as carcinogenesis [2]. Moreover, the Aveloz latex is also responsible for a few important activities against some infectious and neoplastic diseases. Aveloz latex phytochemical composition may vary according to seasonal aspects and geographic location [3], and it is used either orally or topically in traditional medicine. Popularly known as an antitumoral agent (breast, prostate, lung, kidney, it is used not only in Brazil, but in several other countries. According to the literature, the latex could have a dual behaviour, activating or inhibiting tumoral events [3-6]. However, there are few reports discussing these mechanisms. Besides, the mutagenic and genotoxic potentials of phytochemical and homeopathic Aveloz have not yet been described. Several experimental methods have been used to evaluate the mutagenic and genotoxic effects, such as Inductest, the Ames test and the chromotest. Objective: This study aims to evaluate the genotoxic and mutagenic potentials of Aveloz latex and Aveloz phytotherapic and homeopathic solutions. Methodology: In this study, Aveloz 5 and 30cH are prepared according to Brazilian Homeopathic Pharmacopoeia [7], from Aveloz latex collected in the Center for Natural Products Research (NPPN at the Universidade Federal do Rio de Janeiro [8]. The Aveloz phytochemical solution was prepared following the doses used in folk medicine: 2 drops diluted in 250ml of water and 2 drops diluted in 25 ml of water. All test solutions were submitted to the following methodologies: (a Inductest: assesses the ability of physical or chemical agents to promote lysogenic induction as a response to DNA damage in lysogenic bacteria; (b The Ames test: uses indicator strains of Salmonella

  1. Cytotoxicity and genotoxicity of urban particulate matter in mammalian cells.

    Science.gov (United States)

    Dumax-Vorzet, Audrey F; Tate, M; Walmsley, Richard; Elder, Rhod H; Povey, Andrew C

    2015-09-01

    Ambient air particulate matter (PM)-associated reactive oxygen species (ROS) have been linked to a variety of altered cellular outcomes. In this study, three different PM samples from diesel exhaust particles (DEPs), urban dust standard reference material SRM1649a and air collected in Manchester have been tested for their ability to oxidise DNA in a cell-free assay, to increase intracellular ROS levels and to induce CYP1A1 gene expression in mammalian cells. In addition, the cytotoxicity and genotoxicity of PM were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and alkaline comet assay, respectively. All PM samples catalysed the Fenton reaction in a cell-free assay, but only DEP resulted in the generation of ROS as measured by dichlorodihydrofluorescein diacetate oxidation in mammalian cells. However, there was no evidence that increased ROS was a consequence of polycyclic aromatic hydrocarbon metabolism via CYP1A1 induction as urban dust, the Manchester dust samples but not DEP-induced CYP1A1 expression. Urban dust was more cytotoxic in murine embryonic fibroblasts (MEFs) than the other PM samples and also induced expression of GADD45a in the GreenScreen Human Cell assay without S9 activation suggesting the presence of a direct-acting genotoxicant. Urban dust and DEP produced comparable levels of DNA damage, as assessed by the alkaline comet assay, in MEFs at higher levels than those induced by Manchester PM. In conclusion, results from the cytotoxic and genotoxic assays are not consistent with ROS production being the sole determinant of PM-induced toxicity. This suggests that the organic component can contribute significantly to this toxicity and that further work is required to better characterise the extent to which ROS and organic components contribute to PM-induced toxicity.

  2. In Vitro Analysis of Early Genotoxic and Cytotoxic Effects of Okadaic Acid in Different Cell Types of the Mussel Mytilus galloprovincialis.

    Science.gov (United States)

    Prego-Faraldo, María Verónica; Valdiglesias, Vanessa; Laffon, Blanca; Eirín-López, José M; Méndez, Josefina

    2015-01-01

    Okadaic acid (OA) is the predominant biotoxin responsible for diarrhetic shellfish poisoning (DSP) syndrome in humans. While its harmful effects have been extensively studied in mammalian cell lines, the impact on marine organisms routinely exposed to OA is still not fully known. Few investigations available on bivalve molluscs suggest less genotoxic and cytotoxic effects of OA at high concentrations during long exposure times. In contrast, no apparent information is available on how sublethal concentrations of OA affect these organisms over short exposure times. In order to fill this gap, this study addressed for the first time in vitro analysis of early genotoxic and cytotoxic effects attributed to OA in two cell types of the mussel Mytilus galloprovincialis. Accordingly, hemocytes and gill cells were exposed to low OA concentrations (10, 50, 100, 200, or 500 nM) for short periods of time (1 or 2 h). The resulting DNA damage, as apoptosis and necrosis, was subsequently quantified using the comet assay and flow cytometry, respectively. Data demonstrated that (1) mussel hemocytes seem to display a resistance mechanism against early genotoxic and cytotoxic OA-induced effects, (2) mussel gill cells display higher sensitivity to early OA-mediated genotoxicity than hemocytes, and (3) mussel gill cells constitute more suitable systems to evaluate the genotoxic effect of low OA concentrations in short exposure studies. Taken together, this investigation provides evidence supporting the more reliable suitability of mussel gill cells compared to hemocytes to evaluate the genotoxic effect of low short-duration exposure to OA.

  3. Comparative evaluation of genotoxicity of captan in amphibian larvae (Xenopus laevis and Pleurodeles waltl) using the comet assay and the micronucleus test.

    Science.gov (United States)

    Mouchet, F; Gauthier, L; Mailhes, C; Ferrier, V; Devaux, A

    2006-06-01

    Captan (N-trichloromethylthio-4-cyclohexene-1,2-dicarboximide) is a fungicide used to inhibit the growth of many types of fungi on plants used as foodstuffs. The toxic and genotoxic potentials of captan were evaluated with the micronucleus test (MNT; AFNOR,2000) and the comet assay (CA) using amphibian larvae (Xenopus laevis and Pleurodeles waltl). Acute toxicity results showed that captan was toxic (1) to Xenopus larvae exposed to from 2 mg/L to 125 or 62.5 microg/L, depending on the nature of the water [reconstituted water containing mineral salts or mineral water (MW; Volvic, Danone, France)] and (2) to Pleurodeles exposed to from 2 mg/L to 125 microg/L in both types of water. The MNT results obtained in MW showed that captan (62.5 microg/L) was genotoxic to Xenopus but not genotoxic to Pleurodeles at all concentrations tested. CA established that the genotoxicity of captan to Xenopus and Pleurodeles larvae depended on the concentration, the exposure times, and the comet parameters (tail DNA, TEM, OTM, and TL). The CA and MNT results were compared for their ability to detect DNA damage at the concentrations of captan and the exposure times applied. CA showed captan to be genotoxic from the first day of exposure. In amphibians, CA appears to be a sensitive and suitable method for detecting genotoxicity such as that caused by captan.

  4. GENOTOXICITY OF SHALLOW WATERS NEAR THE BRAZILIAN ANTARCTIC STATION "COMANDANTE FERRAZ" (EACF, ADMIRALTY BAY, KING GEORGE ISLAND, ANTARCTICA

    Directory of Open Access Journals (Sweden)

    Arthur José da Silva Rocha

    2015-03-01

    Full Text Available Series of biomonitoring surveys were undertaken weekly in February 2012 to investigate the genotoxicity of the shallow waters around the Brazilian Antarctic Station "Comandante Ferraz" (EACF. The comet assay was applied to assess the damage to the DNA of hemocytes of the crustacean amphipods Gondogeneia antarctica collected from shallow waters near the Fuel Tanks (FT and Sewage Treatment Outflow (STO of the research station, and compare it to the DNA damage of animals from Punta Plaza (PPL and Yellow Point (YP, natural sites far from the EACF defined as experimental controls. The damage to the DNA of hemocytes of G. antarctica was not significantly different between sites in the biomonitoring surveys I and II. In survey III, the damage to the DNA of animals captured in shallow waters near the Fuel Tanks (FT and Sewage Treatment Outflow (STO was significantly higher than that of the control site of Punta Plaza (PPL. In biomonitoring survey IV, a significant difference was detected only between the FT and PPL sites. Results demonstrated that the shallow waters in front of the station may be genotoxic and that the comet assay and hemocytes of G. antarctica are useful tools for assessing genotoxicity in biomonitoring studies of Antarctic marine coastal habitats.

  5. Genotoxicity in earthworm after combined treatment of ionising radiation and mercury

    International Nuclear Information System (INIS)

    This study was performed to investigate the acute genotoxic effects of mercury and radiation on earthworms (Eisenia fetida). The levels of DNA damage and the repair kinetics in the coelomocytes of E. fetida treated with mercuric chloride (HgCl2) and ionising radiation (gamma rays) were analysed by means of the comet assay. For detection of DNA damage and repair, E. fetida was exposed to HgCl2 (0-160 mg kg-1) and irradiated with gamma rays (0-50 Gy) in vivo. The increase in DNA damage depended on the concentration of mercury or dose of radiation. The results showed that the more the oxidative stress induced by mercury and radiation the longer the repair time that was required. When a combination of HgCl2 and gamma rays was applied, the cell damage was much higher than those treated with HgCl2 or radiation alone, which indicated that the genotoxic effects were increased after the combined treatment of mercury and radiation. (authors)

  6. Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes.

    Science.gov (United States)

    Cho, Yoon Hee; Lee, Joong Won; Woo, Hae Dong; Lee, Sunyeong; Kim, Yang Jee; Lee, Younghyun; Shin, Sangah; Joung, Hyojee; Chung, Hai Won

    2016-02-01

    Following one of the world's largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM), a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN) and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 μL/mL), the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 μg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes. PMID:26907305

  7. Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes

    Directory of Open Access Journals (Sweden)

    Yoon Hee Cho

    2016-02-01

    Full Text Available Following one of the world’s largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM, a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 μL/mL, the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 μg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes.

  8. Application of the Single Cell Gel Electrophoresis (SCGE) Assay to Genotoxicity Evaluation in Plants and Animals

    International Nuclear Information System (INIS)

    Application of the Single Cell Gel Electrophoresis (SCGE) Assay to Genotoxicity Evaluation in Plants and Animals. Recently, the importance of ionizing radiation and chemicals has been recognized since radio- and chemical therapy is directly related to the control of various diseases such as cancer. Radiation and the chemicals can cause biological damages while they have great applicability. It is of necessity to analyze rapidly, easily and accurately the biological effects, especially DNA damage due to those factors. Recently SCGE (single cell gel electrophoresis assay, alias comet assay) has been developed for the efficient evaluation of DNA damage. In this report, the comprehensive review will be given on the rationale, the technical applications and the advantages and shortcomings of SCGE assay. This method can be directly applied to study on toxicity, cancer, and aging in terms of the evaluation of DNA damages due to radiation and chemicals on human cellular level. It is also suggested that comet assay be used for testing genotoxicity of suspected substances, detecting irradiated foods, screening radioprotective candidates, and studying DNA repair process in various biological systems

  9. Application of the Single Cell Gel Electrophoresis (SCGE) Assay to Genotoxicity Evaluation in Plants and Animals

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Kyu

    2007-10-15

    Application of the Single Cell Gel Electrophoresis (SCGE) Assay to Genotoxicity Evaluation in Plants and Animals. Recently, the importance of ionizing radiation and chemicals has been recognized since radio- and chemical therapy is directly related to the control of various diseases such as cancer. Radiation and the chemicals can cause biological damages while they have great applicability. It is of necessity to analyze rapidly, easily and accurately the biological effects, especially DNA damage due to those factors. Recently SCGE (single cell gel electrophoresis assay, alias comet assay) has been developed for the efficient evaluation of DNA damage. In this report, the comprehensive review will be given on the rationale, the technical applications and the advantages and shortcomings of SCGE assay. This method can be directly applied to study on toxicity, cancer, and aging in terms of the evaluation of DNA damages due to radiation and chemicals on human cellular level. It is also suggested that comet assay be used for testing genotoxicity of suspected substances, detecting irradiated foods, screening radioprotective candidates, and studying DNA repair process in various biological systems.

  10. The yeast mitogen-activated protein kinase Slt2 is involved in the cellular response to genotoxic stress

    Directory of Open Access Journals (Sweden)

    Soriano-Carot María

    2012-02-01

    Full Text Available Abstract Background The maintenance of genomic integrity is essential for cell viability. Complex signalling pathways (DNA integrity checkpoints mediate the response to genotoxic stresses. Identifying new functions involved in the cellular response to DNA-damage is crucial. The Saccharomyces cerevisiae SLT2 gene encodes a member of the mitogen-activated protein kinase (MAPK cascade whose main function is the maintenance of the cell wall integrity. However, different observations suggest that SLT2 may also have a role related to DNA metabolism. Results This work consisted in a comprehensive study to connect the Slt2 protein to genome integrity maintenance in response to genotoxic stresses. The slt2 mutant strain was hypersensitive to a variety of genotoxic treatments, including incubation with hydroxyurea (HU, methylmetanosulfonate (MMS, phleomycin or UV irradiation. Furthermore, Slt2 was activated by all these treatments, which suggests that Slt2 plays a central role in the cellular response to genotoxic stresses. Activation of Slt2 was not dependent on the DNA integrity checkpoint. For MMS and UV, Slt2 activation required progression through the cell cycle. In contrast, HU also activated Slt2 in nocodazol-arrested cells, which suggests that Slt2 may respond to dNTP pools alterations. However, neither the protein level of the distinct ribonucleotide reductase subunits nor the dNTP pools were affected in a slt2 mutant strain. An analysis of the checkpoint function revealed that Slt2 was not required for either cell cycle arrest or the activation of the Rad53 checkpoint kinase in response to DNA damage. However, slt2 mutant cells showed an elongated bud and partially impaired Swe1 degradation after replicative stress, indicating that Slt2 could contribute, in parallel with Rad53, to bud morphogenesis control after genotoxic stresses. Conclusions Slt2 is activated by several genotoxic treatments and is required to properly cope with DNA damage. Slt

  11. Genotoxic assessment in different exposure groups working with antineoplastic agents

    OpenAIRE

    Ladeira, Carina; Viegas, Susana; Pádua, Mário; Carolino, Elisabete; Gomes, Manuel C.; Brito, Miguel

    2015-01-01

    Antioneoplastic drugs are widely used in treatment of cancer, and several studies suggest acute and long-term effects associated to antineoplastic drug exposures, namely associating workplace exposure with health effects. Cytokinesis blocked micronucleus (CBMN) assay is one promising short-term genotoxicity assays for human risk assessment and their combination is recommended to monitor populations chronically exposed to genotoxic agents. The aim of this investigation is the genotoxicity asse...

  12. Mechanisms of genotoxic effects of hormones

    OpenAIRE

    Đelić Ninoslav J.

    2002-01-01

    A concept that compounds commonly present in biological systems lack genotoxic and mutagenic activities is generally in use, hence a low number of endogenous substances have ever been tested to mutagenicity. Epidemiological and experimental analyses indicated, however, that sexual steroids could contribute to initiation and/or continuation of malign diseases. Detailed studies using methods of biochemistry, molecular biology, cytogenetics and other branches, showed that not only epigenetic mec...

  13. Mechanisms of genotoxic effects of hormones

    Directory of Open Access Journals (Sweden)

    Đelić Ninoslav J.

    2002-01-01

    Full Text Available A concept that compounds commonly present in biological systems lack genotoxic and mutagenic activities is generally in use, hence a low number of endogenous substances have ever been tested to mutagenicity. Epidemiological and experimental analyses indicated, however, that sexual steroids could contribute to initiation and/or continuation of malign diseases. Detailed studies using methods of biochemistry, molecular biology, cytogenetics and other branches, showed that not only epigenetic mechanisms, such as a stimulation of cell proliferation, but also certain hormones, that can express genotoxic effects, such as covalent DNA modification, then chromosomal lesions and chromosomal aberrations, are in the background of malign transformation under activities of hormones. In the case of oestrogens, it was shown that excessive hormonal stimulation led to a metabolic conversion of these hormones to reactive intermediates with formation of reactive oxygenic derivates, so that cells were virtually under conditions of oxidative stress. Individual and tissue susceptibility to occurrence of deterioration of DNA and other cell components generally results from the differences in efficiency of enzymic and non-enzymic mechanisms of resistance against oxidative stress. Besides, steroid thyeroid hormones and catecholamine (dopamine, noradrenaline/norepinephrine and adrenaline can express genotoxic effects in some test-systems. It is interesting that all above mentioned hormones have a phenolic group. Data on possible genotoxic effects of peptide and protein hormones are very scarce, but based on the available literature it is considered that this group of hormones probably lacks mutagenic activities. The possibility that hormones, as endogenous substances, express mutagenic activities results from the fact that DNA is, regardless of chemical and metabolic stability susceptible, to a certain extent, to changeability compatible with the processes of the

  14. Overestimation of nanoparticles-induced DNA damage determined by the comet assay.

    Science.gov (United States)

    Ferraro, Daniela; Anselmi-Tamburini, Umberto; Tredici, Ilenia Giuseppina; Ricci, Vittorio; Sommi, Patrizia

    2016-09-01

    The increasing use of engineered nanoparticles (NPs) in a wide range of commercial products raises concern about the possible risks that NPs pose to human health. Many aspects of the interaction between living cells and NPs are still unclear, and a reliable assessment of NP genotoxicity would be important. One of the most common tests used for genotoxicity is the comet assay, a sensitive method measuring DNA damage in individual cells. The assay was originally developed for soluble molecules, but it is also used in the assessment of genotoxicity of NPs. However, concerns have been raised recently about the reliability of this test in the case of NPs, but no conclusive results have been presented. Using nuclei isolated from human epithelial cells incubated with NPs, we obtained clear evidence of overestimation of NP genotoxicity by the comet assay in the case of CeO2, TiO2, SiO2, and polystyrene NPs. Removal of the NPs in the cytoplasm was effective in eliminating this genotoxicity overestimation (ex post damage) and determining the actual damage produced by the NPs during incubation with the cells (ex ante damage). This method could improve significantly the determination of NP genotoxicity in eukaryotic cells. PMID:26812144

  15. Cytotoxicity and genotoxicity of biogenic silver nanoparticles

    Science.gov (United States)

    Lima, R.; Feitosa, L. O.; Ballottin, D.; Marcato, P. D.; Tasic, L.; Durán, N.

    2013-04-01

    Biogenic silver nanoparticles with 40.3 ± 3.5 nm size and negative surface charge (- 40 mV) were prepared with Fusarium oxysporum. The cytotoxicity of 3T3 cell and human lymphocyte were studied by a TaliTM image-based cytometer and the genotoxicity through Allium cepa and comet assay. The results of BioAg-w (washed) and BioAg-nw (unwashed) biogenic silver nanoparticles showed cytotoxicity exceeding 50 μg/mL with no significant differences of response in 5 and 10 μg/mL regarding viability. Results of genotoxicity at concentrations 5.0 and 10.0 ug/mL show some response, but at concentrations 0.5 and 1.0 μg/mL the washed and unwashed silver nanoparticles did not present any effect. This in an important result since in tests with different bacteria species and strains, including resistant, MIC (minimal inhibitory concentration) had good answers at concentrations less than 1.9 μg/mL. This work concludes that biogenic silver nanoparticles may be a promising option for antimicrobial use in the range where no cyto or genotoxic effect were observed. Furthermore, human cells were found to have a greater resistance to the toxic effects of silver nanoparticles in comparison with other cells.

  16. Bioavailability of genotoxic mixtures in soil

    Energy Technology Data Exchange (ETDEWEB)

    Bordelon, N.; Washburn, K.; He, L.Y.; Donnelly, K.C. [Texas A and M Univ., College Station, TX (United States). Dept. of Veterinary Anatomy and Public Health

    1996-12-31

    Contaminated media at Superfund sites typically consist of complex mixtures of organic and inorganic chemicals which are difficult to characterize, both analytically and toxicologically. The current EPA approach to risk assessment uses solvent extraction to remove chemicals from the soil as a basis for estimating risk to the human population. However, contaminants that can be recovered with a solvent extract may not represent the mixture of chemicals that are available for human exposure. A procedure using an aqueous extraction was investigated to provide a more realistic estimate of what chemicals are bioavailable. A study was conducted with two soil types: creosote-contaminated sandy soil and coal tar-contaminated clay soil spiked with benzo(a)pyrene [B(a)P], and trinitrotoluene (TNT). Samples were extracted with hexane:acetone and water titrated to pH2 and pH7. HPLC analysis demonstrated up to 35% and 29% recovery of contaminants using the aqueous extracts. The estimated cancer risk for the aqueous extract was one order of magnitude less than that for solvent extracts. Analysis using the Salmonella/microsome assay demonstrated that solvent extracts were genotoxic (133 revertants/mg) with metabolic activation while aqueous extracts of clay soil were not genotoxic. Sandy soil showed genotoxicity both with and without metabolic activation. These results suggest that solvent extraction techniques may overestimate the concentration of contaminants that are available for human exposure and, hence, the risk associated with the presence of the contaminants in soil.

  17. Genotoxic effects of copper sulfate in rabbits

    Directory of Open Access Journals (Sweden)

    Georgieva S.

    2013-01-01

    Full Text Available This study was carried out to determine the genotoxic effects of oral application of CuSO4 in rabbits by the chromosome aberration (CA and sister chromatid exchange (SCE tests. Ten male New Zealand rabbits (5 months old, weighing 3.5-4.0 kg were allocated into two groups. The first group received CuSO4 (5H2O in drinking water for 6 consecutive days. The second group was used as a control. On the 7th day, blood samples were taken from the ear marginal vein and the SCE and CA tests in peripheral lymphocytes were used as genotoxicity and mutagenicity endpoints, respectively. Results showed a significant increase in the frequencies of the aberrant cells (7.4±0.24, P<0.001 and CA (chromatid fragments 3.2±0.37, chromosome fragments 4.2±0.37, P<0.001, and total aberrations (7.4±0.24, P<0.001 after the treatment with CuSO4 when compared with the control group. The level of SCE per cell in the CuSO4-treated rabbits (9.66±0.062 was significantly higher than in rabbits from the control group. These findings show that copper exhibits a genotoxic and mutagenic potential in rabbits.

  18. From nanotechnology to nanogenotoxicology: genotoxic effect of cobalt-chromium nanoparticles

    Directory of Open Access Journals (Sweden)

    Zülal Atlı Şekeroğlu

    2013-03-01

    Full Text Available Nanotechnology is a multi-disciplinary technology that processes the materials that can be measured with nanometer-level and combines many research field or discipline. Nanomaterials (NMs are widely used in the fields of science, technology, communication, electronics, industry, pharmacy, medicine, environment, consumer products and military. Until recently little has been known about whether or not nanomaterials have the toxic or hazardous effects on human health and the environment. However, several studies have indicated that exposure to some nanomaterials, e.g. nanoparticles, can cause some adverse effects in humans and animals. Over the last years the number of publications focusing on nanotoxicology has gained momentum, but, there is still a gap about the genotoxicity of nanomaterials.Metal nanoparticles and their alloys with excellent mechanical properties are the materials which can be easily adapted to the mechanical conditions of the musculoskeletal system. Cobalt-chromium alloys are widely used in orthopedic applications as joint prosthesis and bone regeneration material, fillings and dental implants in jaw surgery, and in cardiovascular surgery, especially stent applications. Studies about cytotoxicity and genotoxicity of metal nanoparticles on human indicate that some metal nanoparticles have cytotoxic and genotoxic effects and they may be hazardous for humans. However, a few studies have been reported concerning the genotoxic effects of cobalt-chromium nanoparticles. The data from these studies indicate that cobalt-chromium nanoparticles have cytotoxic and genotoxic effects. It has been stated that the wear debris from implants cause DNA and chromosome damage in patients with cobalt-chromium replacements. It was also found that the risk of urinary cancers such as bladder, ureter, kidney and prostate in patients after hip replacement than among the wider population.Because there are very little biocompatibility and toxicity tests on

  19. Evaluation of genotoxic effect of silver nanoparticles (Ag-Nps) in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Tavares, Priscila; Balbinot, Fernanda; Martins de Oliveira, Hugo; Elibio Fagundes, Gabriela [PPGCS, Universidade do Extremo Sul Catarinense, Laboratorio de Biologia Celular e Molecular (Brazil); Venancio, Mireli; Vieira Ronconi, Joao Vitor; Merlini, Aline [Universidade do Extremo Sul Catarinense, Laboratorio de Sintese de Complexos Multifuncionais (Brazil); Streck, Emilio L. [Programa de Pos-Graduacao em Ciencias da Saude, Unidade Academica de Ciencias da Saude, Universidade do Extremo Sul Catarinense, Laboratorio de Fisiopatologia Experimental (Brazil); Marques da Silva, Paula [Universidade do Extremo Sul Catarinense, Laboratorio de Sintese de Complexos Multifuncionais (Brazil); Moraes de Andrade, Vanessa, E-mail: vmoraesdeandrade@yahoo.com.br [PPGCS, Universidade do Extremo Sul Catarinense, Laboratorio de Biologia Celular e Molecular (Brazil)

    2012-03-15

    Silver nanoparticles (Ag-NPs) are the most prominent nanoproducts. Due to their antimicrobial activity, they have been incorporated in different materials, such as catheters, clothes, electric home appliance, and many others. The genotoxicity of Ag-NPs (5-45 nm), in different concentrations and times of exposure, was evaluated by the comet assay in in vitro and in vivo conditions, respectively, using human peripheral blood and Swiss mice. The results showed the genotoxic effect of Ag-NPs in vitro, in all the doses tested in the initial hour of exposure, possibly through the reactive oxygen species generation. Nevertheless, the values for this damage decrease with time, indicating that the DNA may have been restored by the repair system. In the in vivo conditions, we found no genotoxicity of Ag-NPs in any hour of exposure and any dose investigated, which can be attributed to the activation of a cellular antioxidant network and the hydrophobic nature of Ag-NPs. Now, it is absolutely necessary to investigate the role of Ag-NPs in different cell lines in vivo.

  20. Evaluation of genotoxicity induced by repetitive administration of local anaesthetics: an experimental study in rats

    Directory of Open Access Journals (Sweden)

    Gisele Alborghetti Nai

    2015-02-01

    Full Text Available BACKGROUND AND OBJECTIVE: Previous studies regarding the effects of some local anaesthetics have suggested that these agents can cause genetic damage. However, they have not been tested for genotoxicity related to repetitive administration. The aim of this study was to evaluate the genotoxic potential of local anaesthetics upon repetitive administration. METHODS: 80 male Wistar rats were divided into: group A - 16 rats intraperitoneally injected with lidocaine hydrochloride 2%; group B - 16 rats IP injected with mepivacaine 2%; group C - 16 rats intraperitoneally injected with articaine 4%; group D - 16 rats IP injected with prilocaine 3% (6.0 mg/kg; group E - 8 rats subcutaneously injected with a single dose of cyclophosphamide; and group F - 8 rats intraperitoneally injected with saline. Eight rats from groups A to D received a single dose of anaesthetic on Day 1 of the experiment; the remaining rats were dosed once a day for 5 days. RESULTS: The median number of micronuclei in the local anaesthetics groups exposed for 1 or 5 days ranged from 0.00 to 1.00, in the cyclophosphamide-exposed group was 10.00, and the negative control group for 1 and 5 days was 1.00 and 0.00, respectively (p 0.05. CONCLUSION: No genotoxicity effect was observed upon repetitive exposure to any of the local anaesthetics evaluated.

  1. Evaluation of genotoxic effect of silver nanoparticles (Ag-Nps) in vitro and in vivo

    International Nuclear Information System (INIS)

    Silver nanoparticles (Ag-NPs) are the most prominent nanoproducts. Due to their antimicrobial activity, they have been incorporated in different materials, such as catheters, clothes, electric home appliance, and many others. The genotoxicity of Ag-NPs (5–45 nm), in different concentrations and times of exposure, was evaluated by the comet assay in in vitro and in vivo conditions, respectively, using human peripheral blood and Swiss mice. The results showed the genotoxic effect of Ag-NPs in vitro, in all the doses tested in the initial hour of exposure, possibly through the reactive oxygen species generation. Nevertheless, the values for this damage decrease with time, indicating that the DNA may have been restored by the repair system. In the in vivo conditions, we found no genotoxicity of Ag-NPs in any hour of exposure and any dose investigated, which can be attributed to the activation of a cellular antioxidant network and the hydrophobic nature of Ag-NPs. Now, it is absolutely necessary to investigate the role of Ag-NPs in different cell lines in vivo.

  2. The cyto- and genotoxicity of organotin compounds is dependent on the cellular uptake capability

    International Nuclear Information System (INIS)

    Organotin compounds have been widely used as stabilizers and anti-fouling agents with the result that they are ubiquitously distributed in the environment. Organotins accumulate in the food chain and potential effects on human health are disquieting. It is not known as yet whether cell surface adsorption or accumulation within the cell, or indeed both is a prerequisite for the toxicity of organotin compounds. In this study, the alkylated tin derivatives monomethyltin trichloride (MMT), dimethyltin dichloride (DMT), trimethyltin chloride (TMT) and tetramethyltin (TetraMT) were investigated for cyto- and genotoxic effects in CHO-9 cells in relation to the cellular uptake. To identify genotoxic effects, induction of micronuclei (MN), chromosome aberrations (CA) and sister chromatid exchanges (SCE) were analyzed and the nuclear division index (NDI) was calculated. The cellular uptake was assessed using ICP-MS analysis. The toxicity of the tin compounds was also evaluated after forced uptake by electroporation. Our results show that uptake of the organotin compounds was generally low but dose-dependent. Only weak genotoxic effects were observed after exposure of cells to DMT and TMT. MMT and TetraMT were negative in the test systems. After forced uptake by electroporation MMT, DMT and TMT induced significant DNA damage at non-cytotoxic concentrations. The results presented here indicate a considerable toxicological potential of some organotin species but demonstrate clearly that the toxicity is modulated by the cellular uptake capability

  3. Zebrafish as an in vivo high-throughput model for genotoxicity.

    Science.gov (United States)

    Chakravarthy, Sridhara; Sadagopan, Sathish; Nair, Ayyappan; Sukumaran, Sunil Kumar

    2014-04-01

    Compounds routinely used to increase the quality of life and combat disease undergo stringent potency and biosafety tests before approval. However, based on the outcome of ongoing research, new norms need to be effected to ensure that the compounds conform to biosafety at all target levels of activity. Whereas in vitro tests used to assess biosafety lack the potency and the translational attribute of a whole animal, mammalian preclinical models are expensive and time exhaustive. Zebrafish (Danio rerio) has emerged as an attractive alternative for biosafety studies due to its small size, genetics, breeding capabilities, and most importantly, similarity at the molecular and physiological levels with humans. It has been used extensively for testing various forms of toxicity, including developmental toxicity, cardiotoxicity, nephrotoxicity, and hepatotoxicity. We review here the utility of zebrafish as a powerful, sensitive, quantitative, noninvasive, and high-throughput whole-animal assay to screen for toxicity. Different forms of toxicity will be discussed briefly before we highlight the present state of genotoxicity study in zebrafish. This review, a first in this research area, will serve as a comprehensive introduction to the field of genotoxicity assay using zebrafish, a nascent but promising field that assays compounds for DNA damage. We also discuss possible approaches that could potentially be pursued to overcome some of the shortcomings in current genotoxic studies.

  4. Evaluation of Genotoxic and Cytotoxic Effects in Human Peripheral Blood Lymphocytes Exposed In Vitro to Neonicotinoid Insecticides News

    Science.gov (United States)

    Calderón-Segura, María Elena; Gómez-Arroyo, Sandra; Villalobos-Pietrini, Rafael; Martínez-Valenzuela, Carmen; Carbajal-López, Yolanda; Calderón-Ezquerro, María del Carmen; Cortés-Eslava, Josefina; García-Martínez, Rocío; Flores-Ramírez, Diana; Rodríguez-Romero, María Isabel; Méndez-Pérez, Patricia; Bañuelos-Ruíz, Enrique

    2012-01-01

    Calypso (thiacloprid), Poncho (clothianidin), Gaucho (imidacloprid), and Jade (imidacloprid) are commercial neonicotinoid insecticides, a new class of agrochemicals in México. However, genotoxic and cytotoxic studies have not been performed. In the present study, human peripheral blood lymphocytes (PBL) were exposed in vitro to different concentrations of the four insecticides. The genotoxic and cytotoxic effects were evaluated using the alkaline comet and trypan blue dye exclusion assays. DNA damage was evaluated using two genotoxicity parameters: tail length and comet frequency. Exposure to 9.5 × 10−6 to 5.7 × 10−5 M Jade; 2.8 × 10−4 to 1.7 × 10−3 M Gaucho; 0.6 × 10−1 to 1.4 × 10−1 M Calypso; 1.2 × 10−1 to 9.5 × 10−1 M Poncho for 2 h induced a significant increase DNA damage with a concentration-dependent relationship. Jade was the most genotoxic of the four insecticides studied. Cytotoxicity was observed in cells exposed to 18 × 10−3 M Jade, 2.0 × 10−3 M Gaucho, 2.0 × 10−1 M Calypso, 1.07 M Poncho, and cell death occurred at 30 × 10−3 M Jade, 3.3 × 10−3 M Gaucho, 2.8 × 10−1 M Calypso, and 1.42 M Poncho. This study provides the first report of genotoxic and cytotoxic effects in PBL following in vitro exposure to commercial neonicotinoid insecticides. PMID:22545045

  5. Evaluation of Genotoxic and Cytotoxic Effects in Human Peripheral Blood Lymphocytes Exposed In Vitro to Neonicotinoid Insecticides News

    Directory of Open Access Journals (Sweden)

    María Elena Calderón-Segura

    2012-01-01

    Full Text Available Calypso (thiacloprid, Poncho (clothianidin, Gaucho (imidacloprid, and Jade (imidacloprid are commercial neonicotinoid insecticides, a new class of agrochemicals in México. However, genotoxic and cytotoxic studies have not been performed. In the present study, human peripheral blood lymphocytes (PBL were exposed in vitro to different concentrations of the four insecticides. The genotoxic and cytotoxic effects were evaluated using the alkaline comet and trypan blue dye exclusion assays. DNA damage was evaluated using two genotoxicity parameters: tail length and comet frequency. Exposure to 9.5×10-6 to 5.7×10-5 M Jade; 2.8×10-4 to 1.7×10-3 M Gaucho; 0.6×10-1 to 1.4×10-1 M Calypso; 1.2×10-1 to 9.5×10-1 M Poncho for 2 h induced a significant increase DNA damage with a concentration-dependent relationship. Jade was the most genotoxic of the four insecticides studied. Cytotoxicity was observed in cells exposed to 18×10-3 M Jade, 2.0×10-3 M Gaucho, 2.0×10-1 M Calypso, 1.07 M Poncho, and cell death occurred at 30×10-3 M Jade, 3.3×10-3 M Gaucho, 2.8×10-1 M Calypso, and 1.42 M Poncho. This study provides the first report of genotoxic and cytotoxic effects in PBL following in vitro exposure to commercial neonicotinoid insecticides.

  6. Genotoxicity analysis of two halonitromethanes, a novel group of disinfection by-products (DBPs), in human cells treated in vitro

    International Nuclear Information System (INIS)

    Halonitromethanes (HNMs) constitute an emerging class of disinfection by-products (DBPs) produced when chlorine and/or ozone are used for water treatment. The HNMs are structurally similar to halomethanes, but have a nitro-group in place of hydrogen bonded to the central carbon atom. Since little information exists on the genotoxic potential of HNMs, a study has been carried out with two HNM compounds, namely trichloronitromethane (TCNM) and bromonitromethane (BNM) by using human cells. Primary damage induction has been measured with the Comet assay, which is used to determine both the repair kinetics of the induced damage and the proportion of induced oxidative damage. In addition, the fixed DNA damage has been evaluated by using the micronucleus (MN) assay. The results obtained indicate that both compounds are genotoxic, inducing high levels of DNA breaks in the Comet assay, and that this DNA damage repairs well over time. In addition, oxidized bases constitute a high proportion of DNA-induced damage (50-75%). Contrarily, no positive effects were observed in the frequency of micronucleus, which measures both clastogenic and aneugenic effects, neither using TK6 cells nor peripheral blood lymphocytes. This lack of fixed genetic damage would minimize the potential mutagenic risk associated with HNMs exposure

  7. An integrative assessment to determine the genotoxic hazard of estuarine sediments: combining cell and whole-organism responses

    OpenAIRE

    Costa, Pedro M; Pinto, Miguel; Vicente, Ana M.; Gonçalves, Cátia; Rodrigo, Ana P.; Louro, Henriqueta; MARIA H. COSTA; Caeiro, Sandra; Silva, Maria J.

    2014-01-01

    The application of the Comet assay in environmental monitoring remains challenging in face of the complexity of environmental stressors, e.g., when dealing with estuarine sediments, that hampers the drawing of cause-effect relationships. Although the in vitro Comet assay may circumvent confounding factors, its application in environmental risk assessment (ERA) still needs validation. As such, the present work aims at integrating genotoxicity and oxidative DNA damage induced by sediment-bound ...

  8. Hexavalent chromium is cytotoxic and genotoxic to hawksbill sea turtle cells

    International Nuclear Information System (INIS)

    Sea turtles are a charismatic and ancient ocean species and can serve as key indicators for ocean ecosystems, including coral reefs and sea grass beds as well as coastal beaches. Genotoxicity studies in the species are absent, limiting our understanding of the impact of environmental toxicants on sea turtles. Hexavalent chromium (Cr(VI)) is a ubiquitous environmental problem worldwide, and recent studies show it is a global marine pollutant of concern. Thus, we evaluated the cytotoxicity and genotoxicity of soluble and particulate Cr(VI) in hawksbill sea turtle cells. Particulate Cr(VI) was both cytotoxic and genotoxic to sea turtle cells. Concentrations of 0.1, 0.5, 1, and 5 μg/cm2 lead chromate induced 108, 79, 54, and 7% relative survival, respectively. Additionally, concentrations of 0, 0.1, 0.5, 1, and 5 μg/cm2 lead chromate induced damage in 4, 10, 15, 26, and 36% of cells and caused 4, 11, 17, 30, and 56 chromosome aberrations in 100 metaphases, respectively. For soluble Cr, concentrations of 0.25, 0.5, 1, 2.5, and 5 μM sodium chromate induced 84, 69, 46, 25, and 3% relative survival, respectively. Sodium chromate induced 3, 9, 9, 14, 21, and 29% of metaphases with damage, and caused 3, 10, 10, 16, 26, and 39 damaged chromosomes in 100 metaphases at concentrations of 0, 0.25, 0.5, 1, 2.5, and 5 μM sodium chromate, respectively. These data suggest that Cr(VI) may be a concern for hawksbill sea turtles and sea turtles in general. - Highlights: • Particulate Cr(VI) is cytotoxic and clastogenic to hawksbill sea turtle cells. • Soluble Cr(VI) is cytotoxic and clastogenic to hawksbill sea turtle cells. • Cr(VI) may be a risk factor for hawksbill sea turtle health

  9. Hexavalent chromium is cytotoxic and genotoxic to hawksbill sea turtle cells

    Energy Technology Data Exchange (ETDEWEB)

    Wise, Sandra S., E-mail: sandra.wise@maine.edu [Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States); Maine Center for Toxicology and Environmental Health, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States); Department of Applied Medical Science, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States); Xie, Hong, E-mail: hongxie@usm.maine.edu [Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States); Maine Center for Toxicology and Environmental Health, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States); Department of Applied Medical Science, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States); Fukuda, Tomokazu, E-mail: tomofukuda009@gmail.com [Graduate School of Agricultural Sciences, Tohoku University, Laboratory of Animal Breeding and Genetics, Second Research Building, Rm 112, 1-1 Amamiyamachi, Aoba-ku, Sendai 981-8555 (Japan); Douglas Thompson, W., E-mail: dougt@usm.maine.edu [Maine Center for Toxicology and Environmental Health, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States); Department of Applied Medical Science, University of Southern Maine, Science Building, 96 Falmouth Street, Portland, ME 04103 (United States); and others

    2014-09-01

    Sea turtles are a charismatic and ancient ocean species and can serve as key indicators for ocean ecosystems, including coral reefs and sea grass beds as well as coastal beaches. Genotoxicity studies in the species are absent, limiting our understanding of the impact of environmental toxicants on sea turtles. Hexavalent chromium (Cr(VI)) is a ubiquitous environmental problem worldwide, and recent studies show it is a global marine pollutant of concern. Thus, we evaluated the cytotoxicity and genotoxicity of soluble and particulate Cr(VI) in hawksbill sea turtle cells. Particulate Cr(VI) was both cytotoxic and genotoxic to sea turtle cells. Concentrations of 0.1, 0.5, 1, and 5 μg/cm{sup 2} lead chromate induced 108, 79, 54, and 7% relative survival, respectively. Additionally, concentrations of 0, 0.1, 0.5, 1, and 5 μg/cm{sup 2} lead chromate induced damage in 4, 10, 15, 26, and 36% of cells and caused 4, 11, 17, 30, and 56 chromosome aberrations in 100 metaphases, respectively. For soluble Cr, concentrations of 0.25, 0.5, 1, 2.5, and 5 μM sodium chromate induced 84, 69, 46, 25, and 3% relative survival, respectively. Sodium chromate induced 3, 9, 9, 14, 21, and 29% of metaphases with damage, and caused 3, 10, 10, 16, 26, and 39 damaged chromosomes in 100 metaphases at concentrations of 0, 0.25, 0.5, 1, 2.5, and 5 μM sodium chromate, respectively. These data suggest that Cr(VI) may be a concern for hawksbill sea turtles and sea turtles in general. - Highlights: • Particulate Cr(VI) is cytotoxic and clastogenic to hawksbill sea turtle cells. • Soluble Cr(VI) is cytotoxic and clastogenic to hawksbill sea turtle cells. • Cr(VI) may be a risk factor for hawksbill sea turtle health.

  10. Genotoxicity biomarkers for airborne particulate matter (PM2.5) in an area under petrochemical influence.

    Science.gov (United States)

    Lemos, Andréia Torres; Lemos, Clarice Torres de; Flores, Andressa Negreiros; Pantoja, Eduarda Ozório; Rocha, Jocelita Aparecida Vaz; Vargas, Vera Maria Ferrão

    2016-09-01

    The effects of fine inhalable particles (PM2.5) were evaluated in an area under the influence of a petrochemical industry, investigating the sensitivity of different genotoxicity biomarkers. Organic extracts were obtained from PM2.5 samples at two sites, positioned in the first and second preferential wind direction in the area. The extracts were evaluated with Salmonella/microsome assay, microsuspension method, strains TA98, YG1021 and YG1024. The mammalian metabolization fraction (S9) was used to evaluate metabolite mutagenicity. The Comet Assay (CA) and Micronuclei Test were used in a Chinese hamster lung cell line (V79). All extracts showed mutagenicity in Salmonella, and nitrogenated compounds were strongly present. Genotoxicity were found in CA in almost all extracts and the micronuclei induction at the Site in the first (Autumn 1, Winter 1), and in the second (Spring 2) wind direction. V79 showed cytotoxicity in all samples. The three biomarkers were concordant in characterization Site NO with worse quality, compatible with the greater pollutants dispersion in the first wind direction. All PM2.5 concentrations were lower than those recommended by air quality standards but genotoxic effects were detected in all samples, corroborating that these standards are inadequate as quality indicators. The Salmonella/microsome assay proved sensitive to PM2.5 mutagenicity, with an outstanding influence of nitroarenes and aromatic amines. Analyses using CA and the micronucleus test broadened the levels of response that involve different damage induction mechanisms. Results show that the complex PM2.5 composition can provoke various genotoxic effects and the use of different bioassays is essential to understand its effects. PMID:27343868

  11. Genotoxic evaluation of infusions of Urera baccifera leaves and roots in Allium cepa cells

    Directory of Open Access Journals (Sweden)

    Amanda L. Gindri

    2015-04-01

    Full Text Available Context: The aqueous extracts of Urera baccifera Wedd. leaves and roots are used to inflammatory and infectious diseases in Brazilian folk medicine. Oxalic acid, a substance co-related with toxicity and stinging, was already quantified in this plant. Aims: To evaluate the action of leaves and roots infusions (1, 30, 75 g/L and the oxalic acid standard on mitosis as indicative of presumably antimitotic and genotoxic actions, using the Allium cepa test. Methods: Oxalic acid was quantified in the roots and leaves infusions by High-performance liquid chromatography (HPLC-DAD, with the mobile phase of 25 mM phosphate buffer (pH 2.5: acetonitrile at 95:5 (v/v. To the genotoxicity test, onion bulbs were used. After the rootlets germination, each bulb was submitted for 24 h of the individual treatments. Were analyzed 1000 cells per bulb, in a total of 5000 cells per treatment. Results: Results showed that all concentrations of roots infusions induced chromosomes abnormalities, except for the highest, that caused a substantial inhibition in the mitosis, precluding to be observed abnormalities. In the leaves infusions, only the two higher concentrations caused the highest values of damage in the cellular cycle. The oxalic acid also caused abnormalities in the mitosis, and may be considered responsible by part of the genotoxic action of U. baccifera. Conclusions: Oxalic acid can be responsible by part of the chromosomal abnormalities caused by U. baccifera, although, there must have more metabolites that evoke the same effect promoting the genotoxic effect of this nettle.

  12. Genotoxicity assessments of alluvial soil irrigated with wastewater from a pesticide manufacturing industry.

    Science.gov (United States)

    Anjum, Reshma; Krakat, Niclas

    2015-10-01

    In this study, organochlorine pesticides (OCP) and heavy metals were analyzed from wastewater- and groundwater- irrigated soils (control samples) by gas chromatography (GC) and atomic absorption spectrophotometry (AAS), respectively. Gas chromatographic analysis revealed the presence of high concentration of pesticides in soil irrigated with wastewater (WWS). These concentrations were far above the maximum residue permissible limits indicating that alluvial soils have high binding capacity of OCP. AAS analyses revealed higher concentration of heavy metals in WWS as compared to groundwater (GWS). Also, the DNA repair (SOS)-defective Escherichia coli K-12 mutant assay and the bacteriophage lambda system were employed to estimate the genotoxicity of soils. Therefore, soil samples were extracted by hexane, acetonitrile, methanol, chloroform, and acetone. Both bioassays revealed that hexane-extracted soils from WWS were most genotoxic. A maximum survival of 15.2% and decline of colony-forming units (CFUs) was observed in polA mutants of DNA repair-defective E. coli K-12 strains when hexane was used as solvent. However, the damage of polA (-) mutants triggered by acetonitrile, methanol, chloroform, and acetone extracts was 80.0, 69.8, 65.0, and 60.7%, respectively. These results were also confirmed by the bacteriophage λ test system as hexane extracts of WWS exhibited a maximum decline of plaque-forming units for lexA mutants of E. coli K-12 pointing to an elevated genotoxic potential. The lowest survival was observed for lexA (12%) treated with hexane extracts while the percentage of survival was 25, 49.2, 55, and 78% with acetonitrile, methanol, chloroform, and acetone, respectively, after 6 h of treatment. Thus, our results suggest that agricultural soils irrigated with wastewater from pesticide industries have a notably high genotoxic potential. PMID:26394621

  13. Qualitative and quantitative approaches in the dose-response assessment of genotoxic carcinogens.

    Science.gov (United States)

    Fukushima, Shoji; Gi, Min; Kakehashi, Anna; Wanibuchi, Hideki; Matsumoto, Michiharu

    2016-05-01

    Qualitative and quantitative approaches are important issues in field of carcinogenic risk assessment of the genotoxic carcinogens. Herein, we provide quantitative data on low-dose hepatocarcinogenicity studies for three genotoxic hepatocarcinogens: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and N-nitrosodiethylamine (DEN). Hepatocarcinogenicity was examined by quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci, which are the preneoplastic lesions in rat hepatocarcinogenesis and the endpoint carcinogenic marker in the rat liver medium-term carcinogenicity bioassay. We also examined DNA damage and gene mutations which occurred through the initiation stage of carcinogenesis. For the establishment of points of departure (PoD) from which the cancer-related risk can be estimated, we analyzed the above events by quantitative no-observed-effect level and benchmark dose approaches. MeIQx at low doses induced formation of DNA-MeIQx adducts; somewhat higher doses caused elevation of 8-hydroxy-2'-deoxyquanosine levels; at still higher doses gene mutations occurred; and the highest dose induced formation of GST-P positive foci. These data indicate that early genotoxic events in the pathway to carcinogenesis showed the expected trend of lower PoDs for earlier events in the carcinogenic process. Similarly, only the highest dose of IQ caused an increase in the number of GST-P positive foci in the liver, while IQ-DNA adduct formation was observed with low doses. Moreover, treatment with DEN at low doses had no effect on development of GST-P positive foci in the liver. These data on PoDs for the markers contribute to understand whether genotoxic carcinogens have a threshold for their carcinogenicity. The most appropriate approach to use in low dose-response assessment must be approved on the basis of scientific judgment.

  14. The Genotoxic and Cytotoxic Effects of Bisphenol-A (BPA) in MCF-7 Cell Line and Amniocytes.

    Science.gov (United States)

    Aghajanpour-Mir, Seyed Mohsen; Zabihi, Ebrahim; Akhavan-Niaki, Haleh; Keyhani, Elahe; Bagherizadeh, Iman; Biglari, Sajjad; Behjati, Farkhondeh

    2016-01-01

    Bisphenol-A (BPA) is an industrial xenoestrogen used widely in our living environment. Recently, several studies suggested that BPA has destructive effects on DNA and chromosomes in normal body cells via estrogen receptors (ER). Therefore, BPA could be considered as an important mediator in many diseases such as cancer. However, there are still many controversial issues which need clarification. In this study, we investigated the BPA-induced chromosomal damages in MCF-7 cell line, ER-positive and negative amniocyte cells. Cytotoxicity and genotoxicity effects of BPA were also compared between these three cell groups. Expression of estrogen receptors was determined using immunocytochemistry technique. The cell cytotoxicity of BPA was measured by MTT assay. Classic cytogenetic technique was carried out for the investigation of chromosome damage. BPA, in addition to cytotoxicity, had remarkable genotoxicity at concentrations close to the traceable levels in tissues or biological fluids. Although some differences were observed in the amount of damages between ER-positive and negative fetal cells, interestingly, these differences were not significant. The present study showed that BPA could lead to chromosomal aberrations in both ER-dependent and independent pathways at some concentrations or in cell types yet not reported. Also, BPA could probably be considered as a facilitator for some predisposed cells to be cancerous by raising the chromosome instability levels. Finally, estrogen receptor seems to have a different role in cytotoxicity and genotoxicity effects. PMID:27386435

  15. Antiproliferative, genotoxic and oxidant activities of cyclosativene in rat neuron and neuroblastoma cell lines

    Directory of Open Access Journals (Sweden)

    Toğar Başak

    2014-01-01

    Full Text Available Cyclosativene (CSV is a tetracyclic sesquiterpene found in the essential oils of Centaurea cineraria (Asteraceae and Abies magnifica A. Murray (Pinaceae plants. To the best of our knowledge, its cytotoxic, genotoxic and oxidant effects have never been studied on any cell lines. Therefore, we aimed to investigate the in vitro antiproliferative and/or cytotoxic properties, antioxidant/oxidant activity and genotoxic damage potential of CSV in healthy neurons and N2a neuroblastoma (N2a-NB cell cultures. After treatment with 10-400 μg/ml of CSV for 24 h, cell proliferation was measured by the MTT (3,(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. The antioxidant activity was assessed by the total antioxidant capacity (TAC and total oxidative stress (TOS assays. To evaluate the level of DNA damage, single cell gel alkaline electrophoresis (SCGE was used. The MTT assay showed that the application of CSV significantly reduced cell viability in both cell types. CSV treatments at higher doses led to decreases of TAC levels and increases of TOS levels in neuron and N2a-NB cells. The mean values of the total scores of cells showing DNA damage were not found to be significantly different from the control values in both cells. In conclusion, this study suggests that CSV has weak anticancer potential.

  16. Micronuclei as biomarkers of genotoxicity of gamma radiation in aquatic environments

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Luanna R.S.; Silva, Edvane B.; Melo, Ana M.M.A. [Universidade Federal de Pernambuco (GERAR/DEN/UFPE), Recife, PE (Brazil). Dept. de Energia Nuclear. Grupo de Estudos em Radioprotecao e Radioecologia; Silva, Ronaldo C. da [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Genetica; Amancio, Francisco F. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Biofisica e Radiobiologia. Lab. de Radiobiologia

    2011-07-01

    Ionizing radiation is a genotoxic agent, inducing gene mutations and cellular death. Several efforts have been defendants in the development of techniques for measurement of radiation damage in biological systems. Among these techniques, micronuclei test has been showing as a great bio marker of DNA damage, being used in environmental monitoring to detect genotoxic agents in the environment. Additionally, organisms as Biomphalaria glabrata, freshwater molluscs, presents itself as an excellent model to assess damage caused by physical and chemical agents, due their biological and environmental characteristics. The snails were divided into groups of 5 individuals exposed to doses of 0 (control), 25, 35, 45 and 55 Gy of {sup 60}Co. After 48 hours of irradiation, the hemo lymph was collected and prepared the slides, which were stained with Giemsa and analyzed the cellular changes in haemocytes Statistical analysis was accomplished through chi-square test, ANOVA and Tukey test (p< 0,05). The results indicated that B. glabrata showed to be sensitive to gamma radiation. The snails irradiated with 35 Gy showed a decrease of haemocytes, while that of 55 Gy increased. Cellular and morphological changes were observed at doses of 35, 45 and 55 Gy and the dose of 55 Gy, the most radiotoxic. (author)

  17. Evaluation of genotoxicity of combined soil pollution by cadmium and phenanthrene on earthworm

    Institute of Scientific and Technical Information of China (English)

    ZHU Jiang; ZHAO Zuo-yuan; LU Yi-tong

    2006-01-01

    The DNA-damaging effects of the combined pollution of heavy metal and organic contamination on earthworms were evaluated by single cell gel electrophoresis (SCGE) assay. Earthworms Eisenia andrei were exposed to single or combined test compounds in different doses of cadmium (Cd) 5, 10, 50 mg/kg and phenanthrene (Phe) 0.5, 2.5, 12.5 mg/kg with a treatment of 14 d.In SCGE assay, isolated coelomcytes and electrophoresis were employed to determine DNA damage degree after a 14-d treatment by test compounds. The results showed that there was a significant statistical difference between earthworms treated with Cd combined Phe with them treated alone with Cd or Phe. The Olive tail moment (OTM) of SCGE assay using earthworm coelomcytes appears to be a sensitive biomarker for evaluating exposure to genotoxic compounds. These tests also revealed that the interaction between Cd and Phe to DNA damaging effects was negative, and was strongly dependent on the concentration of pollution. This study corresponds to exploratory phase in order to reveal interaction effects of heavy metal and organic contamination on earthworms and then to set up more in-depth analysis to increase progressively the understanding of the genotoxicity mechanisms involved.

  18. Micronuclei as biomarkers of genotoxicity of gamma radiation in aquatic environments

    International Nuclear Information System (INIS)

    Ionizing radiation is a genotoxic agent, inducing gene mutations and cellular death. Several efforts have been defendants in the development of techniques for measurement of radiation damage in biological systems. Among these techniques, micronuclei test has been showing as a great bio marker of DNA damage, being used in environmental monitoring to detect genotoxic agents in the environment. Additionally, organisms as Biomphalaria glabrata, freshwater molluscs, presents itself as an excellent model to assess damage caused by physical and chemical agents, due their biological and environmental characteristics. The snails were divided into groups of 5 individuals exposed to doses of 0 (control), 25, 35, 45 and 55 Gy of 60Co. After 48 hours of irradiation, the hemo lymph was collected and prepared the slides, which were stained with Giemsa and analyzed the cellular changes in haemocytes Statistical analysis was accomplished through chi-square test, ANOVA and Tukey test (p< 0,05). The results indicated that B. glabrata showed to be sensitive to gamma radiation. The snails irradiated with 35 Gy showed a decrease of haemocytes, while that of 55 Gy increased. Cellular and morphological changes were observed at doses of 35, 45 and 55 Gy and the dose of 55 Gy, the most radiotoxic. (author)

  19. Evaluation of genotoxic effects of the herbicide dicamba using in vivo and in vitro test systems

    International Nuclear Information System (INIS)

    The genotoxic effects of the herbicide dicamba have been studied by measuring (1) the unwinding rate of liver DNA from intraperitoneally treated rats (fluorimetric assay); (2) DNA repair as unscheduled DNA synthesis (UDS) induced in cultured human peripheral blood lymphocytes (HPBL); and (3) sister chromatid exchanges (SCE) in HPBL. Results show that dicamba is capable of inducing DNA damage since it significantly increases the unwinding rate of rat liver DNA in vivo and also induces UDS in HPBL in vitro in the presence of exogenous metabolic activation (S-9 mix). Furthermore, dicamba causes a very slight increase in SCE frequency in HPBL in vitro

  20. Comet assay to assess the genotoxicity of Persian walnut (Juglans regia L.) husks with statistical evaluation.

    Science.gov (United States)

    Petriccione, Milena; Ciniglia, Claudia

    2012-07-01

    The aim of this study was to confirm the utility of the Comet assay as a genotoxicity screening test for evaluating the impact of walnut husk aqueous extract. Phytotoxicity assays using diluted and undiluted walnut husk aqueous extracts were performed on young roots of Raphanus sativus (radish), and the Comet assay was used to evaluate DNA integrity in isolated radish radicle nuclei. The results reveal a dose-dependent accumulation of DNA damage in radish radicles treated with walnut husks water extract and that the Kolmogorov-Smirnov test combined with Johnson SB distribution was the best approach for describing Comet assay data.

  1. Genotoxic monitoring of workers at a hazardous waste disposal site in Mexico.

    Science.gov (United States)

    Gonsebatt, M E; Salazar, A M; Montero, R; Díaz Barriga, F; Yáñez, L; Gómez, H; Ostrosky-Wegman, P

    1995-01-01

    Chromosomal aberration and sister chromatid exchange (SCE) frequencies were determined in lymphocytes cultured from 12 high-risk individuals working at a landfill for hazardous waste disposal. Cell proliferation kinetics (CPK) was also determined. Compared with 7 control individuals, no effects were observed with respect to SCE nor on CPK. However, the workers exhibited significantly higher frequencies of chromatid and chromosomal deletions, the magnitude of which was related with exposure time. This study suggests that when high-risk exposure is suspected, determining biomarkers of genotoxic damage (e.g., chromosomal aberrations), is useful for risk assessments. PMID:7621789

  2. DNA damage and oxidative stress in marine gastropod Morula granulata exposed to phenanthrene

    Digital Repository Service at National Institute of Oceanography (India)

    Bhagat, J.; Sarkar, A.; Ingole, B.S.

    and DNA damage (TDNA) were the most sensitive in response to phenanthrene exposure. Our results clearly showed that phenanthrene is genotoxic to gastropods and also causes oxidative stress. Keywords: Gastropods; genotoxicity; biomarker; antioxidant... around the world (Souid et al., 2013; Regoli and Giuliani, 2014). Antioxidant enzymatic defences are useful biomarkers of pollution by PAH that generate oxidative stress in marine organisms (Niyogi et al., 2001a, b; Pan et al., 2006). Phenanthrene...

  3. Genotoxicity of Thermopsis turcica on Allium cepa L. roots revealed by alkaline comet and random amplified polymorphic DNA assays.

    Science.gov (United States)

    Ciğerci, İbrahim Hakkı; Cenkci, Süleyman; Kargıoğlu, Mustafa; Konuk, Muhsin

    2016-08-01

    This study was undertaken to evaluate genotoxic potential of Thermopsis turcica aqueous extracts on the roots of onion bulb (Allium cepa L.) by comet assay and random amplified polymorphic DNA technique. The Allium root growth inhibition test indicated that the EC50 and 2×EC50 values were 8 and 16 mg/ml concentrations of T. turcica aqueous extracts, respectively. The negative control (distilled water), positive control (methyl methane sulfonate, 10 mg/l) and 8 and 16 mg/ml concentrations of T. turcica extracts were introduced to the roots of onion bulbs for 24 and 96 h. The root growth, DNA damage in root cells and randomly amplified polymorphic DNA (RAPD) profiles of root tissue were used as endpoints of the genotoxicity. The comet assay clearly indicated that dose-dependent single strand DNA breaks in the root nuclei of onions were determined for the treatment concentrations of T. turcica extracts. In comparison to RAPD profile of negative control group, RAPD polymorphisms became evident as disappearance and/or appearance of RAPD bands in treated roots. The diagnostic and phenetic numerical analyses of RAPD profiles obviously indicated dose-dependent genotoxicity induced by Thermopsis extracts. In conclusion, the results clearly indicated that water extract of T. turcica has genotoxic potential on the roots of onion bulbs as shown by comet assay and RAPD technique. PMID:25550040

  4. Embryotoxic and genotoxic effects of heavy metals and pesticides on early life stages of Pacific oyster (Crassostrea gigas)

    International Nuclear Information System (INIS)

    Highlights: ► Impact of pesticides and heavy metals on early life stage of Pacific oyster. ► Toxicity investigated using embryolarvae and comet assays. ► Relationship between embryotoxicity and genotoxicty. ► Genotoxic and embryotoxic effects at enviromnental pollutant concentrations. - Abstract: This study evaluated embryotoxicity and genotoxicity of two dissolved metals copper and cadmium (Cu and Cd) and two pesticides (metolachlor and irgarol) occurring in Arcachon Bay (SW France) in Pacific oyster (Crassostrea gigas) larvae and investigated the relationship between those two endpoints. Embryotoxicity was measured by calculating the percentage of abnormal D-shaped larvae and genotoxicity was evaluated with DNA strand breaks using the comet assay. After 24 h exposure, significant increases of the percentage of abnormal D-larvae and the DNA strand breaks were observed from 0.1 μg L−1 for Cu, 10 μg L−1 for Cd and 0.01 μg L−1 for both irgarol and metolachlor in comparison with the controls. A strong positive relationship between embryotoxicity and genotoxicity was recorded for Cu, Cd and metolachlor. The current study suggests that copper, irgarol and metolachlor can induce larval abnormalities and DNA damage in a population of exposed oysters at environmentally relevant concentrations.

  5. In vivo studies on genotoxicity of a soil fumigant, dazomet.

    Science.gov (United States)

    Peluso, M; Bolognesi, C; Munnia, A; Landini, E; Parodi, S

    1998-01-01

    Dazomet is a soil fumigant effective against germinating weed seeds, nematodes, soil fungi, and soil insects. Dazomet is primarily used for preplanting control in tobacco and forest nursery crops and is now marketed for a wider range of open field and greenhouse crops (e.g., vegetables, fruits, ornamental plants, lawns, and turfs). Swiss CD1 male and female mice were intraperitoneally treated with dazomet in order to evaluate its potential genotoxicity. DNA damage activity, namely, DNA single-strand breaks, DNA adducts, and increased micronuclei frequency due to treatment with the soil fumigant was observed in the experimental animals. Dose-dependent DNA adduct formation was detected in the liver, kidneys, and lungs of mice. DNA adduct levels in these three organs were 6.0 +/- 0.4 (SD), 4.8 +/- 0.1 (SD), and 2.2 +/- 0.4 (SD) adducts/10(8) nucleotides, respectively, at the highest dose of the soil fumigant tested (90 mg/kg). No adduct formation was observed in control mice. A significant increase in DNA single-strand breaks was detected in the liver and kidneys of mice treated with 100 mg/kg of dazomet (P dazomet (P < 0.05). PMID:9776181

  6. Effect of the nano-bio interface on the genotoxicity of titanium dioxide nanoparticles and associated cellular responses

    Science.gov (United States)

    Prasad, Raju Yashaswi

    Several toxicological studies have shown that titanium dioxide nanoparticles (nano-TiO2), one of the most widely produced engineered nanoparticles, can induce genotoxicity; however, potential adverse health effects associated with their physicochemical properties are not fully understood. Proteins in a biological medium can adsorb to the surface of the nanoparticle resulting in the formation of a protein corona that can alter the physicochemical properties of the particle. Furthermore, the protein corona may impact the interaction between nanoparticles and cells, referred to as the nano-bio interface, effecting the uptake, distribution, and toxicity of the particles. Despite the potential influence of the composition of the biological medium on the physicochemical properties and genotoxicity of titanium dioxide nanoparticles, the majority of studies have not examined systematically the influence of medium composition on protein corona, genotoxicity, and cellular responses. In this dissertation we tested the overall hypothesis that titanium dioxide nanoparticles in medium that produces the smallest agglomerates would be taken up into cells and induce genotoxicity, and that exposure would initiate the signaling of key mediators of a DNA damage and inflammation response. Three major findings were shown in this study: 1) Protein corona formation on the surface of nano-TiO2 can impact the nano-bio interface and change cellular interaction. 2) Smaller agglomerates of nano-TiO2 are taken up more by cells without inducing cell cycle arrest, thereby allowing induced DNA damage to be processed into micronuclei in BEAS-2B cells. 3) Nano-TiO 2 in medium that facilitates increased cellular interaction induces the upregulation of the ATM-Chk2 DNA damage response (similar to ionizing radiation) and NF-kappaB inflammation pathways. Taken together, our research provides a systematic examination of the physicochemical properties, genotoxicity, and cellular responses induced by

  7. Carbon black nanoparticle instillation induces sustained inflammation and genotoxicity in mouse lung and liver

    DEFF Research Database (Denmark)

    Bourdon, Julie A; Saber, Anne T; Jacobsen, Nicklas R;

    2012-01-01

    Widespread occupational exposure to carbon black nanoparticles (CBNPs) raises concerns over their safety. CBNPs are genotoxic in vitro but less is known about their genotoxicity in various organs in vivo.......Widespread occupational exposure to carbon black nanoparticles (CBNPs) raises concerns over their safety. CBNPs are genotoxic in vitro but less is known about their genotoxicity in various organs in vivo....

  8. Mechanistic evaluation of Ginkgo biloba leaf extract-induced genotoxicity in L5178Y cells.

    Science.gov (United States)

    Lin, Haixia; Guo, Xiaoqing; Zhang, Suhui; Dial, Stacey L; Guo, Lei; Manjanatha, Mugimane G; Moore, Martha M; Mei, Nan

    2014-06-01

    Ginkgo biloba has been used for many thousand years as a traditional herbal remedy and its extract has been consumed for many decades as a dietary supplement. Ginkgo biloba leaf extract is a complex mixture with many constituents, including flavonol glycosides and terpene lactones. The National Toxicology Program 2-year cancer bioassay found that G. biloba leaf extract targets the liver, thyroid gland, and nose of rodents; however, the mechanism of G. biloba leaf extract-associated carcinogenicity remains unclear. In the current study, the in vitro genotoxicity of G. biloba leaf extract and its eight constituents was evaluated using the mouse lymphoma assay (MLA) and Comet assay. The underlying mechanisms of G. biloba leaf extract-associated genotoxicity were explored. Ginkgo biloba leaf extract, quercetin, and kaempferol resulted in a dose-dependent increase in the mutant frequency and DNA double-strand breaks (DSBs). Western blot analysis confirmed that G. biloba leaf extract, quercetin, and kaempferol activated the DNA damage signaling pathway with increased expression of γ-H2AX and phosphorylated Chk2 and Chk1. In addition, G. biloba leaf extract produced reactive oxygen species and decreased glutathione levels in L5178Y cells. Loss of heterozygosity analysis of mutants indicated that G. biloba leaf extract, quercetin, and kaempferol treatments resulted in extensive chromosomal damage. These results indicate that G. biloba leaf extract and its two constituents, quercetin and kaempferol, are mutagenic to the mouse L5178Y cells and induce DSBs. Quercetin and kaempferol likely are major contributors to G. biloba leaf extract-induced genotoxicity.

  9. Cytotoxicity and Genotoxicity of Ceria Nanoparticles on Different Cell Lines in Vitro

    Directory of Open Access Journals (Sweden)

    Sandro Santucci

    2013-02-01

    Full Text Available Owing to their radical scavenging and UV-filtering properties, ceria nanoparticles (CeO2-NPs are currently used for various applications, including as catalysts in diesel particulate filters. Because of their ability to filter UV light, CeO2-NPs have garnered significant interest in the medical field and, consequently, are poised for use in various applications. The aim of this work was to investigate the effects of short-term (24 h and long-term (10 days CeO2-NP exposure to A549, CaCo2 and HepG2 cell lines. Cytotoxicity assays tested CeO2-NPs over a concentration range of 0.5 μg/mL to 5000 μg/mL, whereas genotoxicity assays tested CeO2-NPs over a concentration range of 0.5 μg/mL to 5000 μg/mL. In vitro assays showed almost no short-term exposure toxicity on any of the tested cell lines. Conversely, long-term CeO2-NP exposure proved toxic for all tested cell lines. NP genotoxicity was detectable even at 24-h exposure. HepG2 was the most sensitive cell line overall; however, the A549 line was most sensitive to the lowest concentration tested. Moreover, the results confirmed the ceria nanoparticles’ capacity to protect cells when they are exposed to well-known oxidants such as H2O2. A Comet assay was performed in the presence of both H2O2 and CeO2-NPs. When hydrogen peroxide was maintained at 25 μM, NPs at 0.5 μg/mL, 50 μg/mL, and 500 μg/mL protected the cells from oxidative damage. Thus, the NPs prevented H2O2-induced genotoxic damage.

  10. Beryllium metal I. experimental results on acute oral toxicity, local skin and eye effects, and genotoxicity.

    Science.gov (United States)

    Strupp, Christian

    2011-01-01

    The toxicity of soluble metal compounds is often different from that of the parent metal. Since no reliable data on acute toxicity, local effects, and mutagenicity of beryllium metal have ever been generated, beryllium metal powder was tested according to the respective Organisation for Economical Co-Operation and Development (OECD) guidelines. Acute oral toxicity of beryllium metal was investigated in rats and local effects on skin and eye in rabbits. Skin-sensitizing properties were investigated in guinea pigs (maximization method). Basic knowledge about systemic bioavailability is important for the design of genotoxicity tests on poorly soluble substances. Therefore, it was necessary to experimentally compare the capacities of beryllium chloride and beryllium metal to form ions under simulated human lung conditions. Solubility of beryllium metal in artificial lung fluid was low, while solubility in artificial lysosomal fluid was moderate. Beryllium chloride dissolution kinetics were largely different, and thus, metal extracts were used in the in vitro genotoxicity tests. Genotoxicity was investigated in vitro in a bacterial reverse mutagenicity assay, a mammalian cell gene mutation assay, a mammalian cell chromosome aberration assay, and an unscheduled DNA synthesis (UDS) assay. In addition, cell transformation was tested in a Syrian hamster embryo cell assay, and potential inhibition of DNA repair was tested by modification of the UDS assay. Beryllium metal was found not to be mutagenic or clastogenic based on the experimental in vitro results. Furthermore, treatment with beryllium metal extracts did not induce DNA repair synthesis, indicative of no DNA-damaging potential of beryllium metal. A cell-transforming potential and a tendency to inhibit DNA repair when the cell is severely damaged by an external stimulus were observed. Beryllium metal was also found not to be a skin or eye irritant, not to be a skin sensitizer, and not to have relevant acute oral

  11. Genotoxicity of nano/microparticles in in vitro micronuclei, in vivo comet and mutation assay systems

    Directory of Open Access Journals (Sweden)

    Fukumori Nobutaka

    2009-09-01

    Full Text Available Abstract Background Recently, manufactured nano/microparticles such as fullerenes (C60, carbon black (CB and ceramic fiber are being widely used because of their desirable properties in industrial, medical and cosmetic fields. However, there are few data on these particles in mammalian mutagenesis and carcinogenesis. To examine genotoxic effects by C60, CB and kaolin, an in vitro micronuclei (MN test was conducted with human lung cancer cell line, A549 cells. In addition, DNA damage and mutations were analyzed by in vivo assay systems using male C57BL/6J or gpt delta transgenic mice which were intratracheally instilled with single or multiple doses of 0.2 mg per animal of particles. Results In in vitro genotoxic analysis, increased MN frequencies were observed in A549 cells treated with C60, CB and kaolin in a dose-dependent manner. These three nano/microparticles also induced DNA damage in the lungs of C57BL/6J mice measured by comet assay. Moreover, single or multiple instillations of C60 and kaolin, increased either or both of gpt and Spi- mutant frequencies in the lungs of gpt delta transgenic mice. Mutation spectra analysis showed transversions were predominant, and more than 60% of the base substitutions occurred at G:C base pairs in the gpt genes. The G:C to C:G transversion was commonly increased by these particle instillations. Conclusion Manufactured nano/microparticles, CB, C60 and kaolin, were shown to be genotoxic in in vitro and in vivo assay systems.

  12. Epidermal stem cells response to radiative genotoxic stress

    International Nuclear Information System (INIS)

    Human skin is the first organ exposed to various environmental stresses, which requires the development by skin stem cells of specific mechanisms to protect themselves and to ensure tissue homeostasis. As stem cells are responsible for the maintenance of epidermis during individual lifetime, the preservation of genomic integrity in these cells is essential. My PhD aimed at exploring the mechanisms set up by epidermal stem cells in order to protect themselves from two genotoxic stresses, ionizing radiation (Gamma Rays) and ultraviolet radiation (UVB). To begin my PhD, I have taken part of the demonstration of protective mechanisms used by keratinocyte stem cells after ionizing radiation. It has been shown that these cells are able to rapidly repair most types of radiation-induced DNA damage. Furthermore, we demonstrated that this repair is activated by the fibroblast growth factor 2 (FGF2). In order to know if this protective mechanism is also operating in cutaneous carcinoma stem cells, we investigated the response to gamma Rays of carcinoma stem cells isolated from a human carcinoma cell line. As in normal keratinocyte stem cells, we demonstrated that cancer stem cells could rapidly repair radio-induced DNA damage. Furthermore, fibroblast growth factor 2 also mediates this repair, notably thanks to its nuclear isoforms. The second project of my PhD was to study human epidermal stem cells and progenitors responses to UVB radiation. Once cytometry and irradiation conditions were set up, the toxicity of UVB radiation has been evaluate in the primary cell model. We then characterized UVB photons effects on cell viability, proliferation and repair of DNA damage. This study allowed us to bring out that responses of stem cells and their progeny to UVB are different, notably at the level of part of their repair activity of DNA damage. Moreover, progenitors and stem cells transcriptomic responses after UVB irradiation have been study in order to analyze the global

  13. In-Vitro Carbofuran Induced Genotoxicity in Human Lymphocytes and Its Mitigation by Vitamins C and E

    Directory of Open Access Journals (Sweden)

    Ratnesh Kumar Sharma

    2012-01-01

    Full Text Available Various efforts have been made in past in order to predict the underlying mechanism of pesticide-induced toxicity using in vitro and animal models, however, these predictions may or may not be directly correlated with humans. The present study was designed to investigate the carbofuran induced genotoxicity and its amelioration by vitamins C and E by treating human peripheral blood lymphocytes (PBLs with different concentrations (0, 0.5, 1.25, 2.5, 3.75 and 5.0 μM of this compound. The treatment of PBLs with carbofuran displayed significant DNA damage in concentration dependent manner. The carbofuran induced genotoxicity could be ameliorated to considerable extent by pretreatment of PBLs with equimolar (10 μM concentration of each of the vitamins C and E; the magnitude of protection by vitamin E being higher than by vitamin C. Also, it was found that the level of protection by these vitamins was higher when PBLs were treated with lower concentrations of pesticide. The significant DNA damage as observed by H2O2, a positive control in the present study, and its amelioration by natural antioxidants (vitamins C and E lend an evidence to suggest that carbofuran would have caused genotoxicity via pesticide induced oxidative stress.

  14. In-vitro carbofuran induced genotoxicity in human lymphocytes and its mitigation by vitamins C and E.

    Science.gov (United States)

    Sharma, Ratnesh Kumar; Sharma, Bechan

    2012-01-01

    Various efforts have been made in past in order to predict the underlying mechanism of pesticide-induced toxicity using in vitro and animal models, however, these predictions may or may not be directly correlated with humans. The present study was designed to investigate the carbofuran induced genotoxicity and its amelioration by vitamins C and E by treating human peripheral blood lymphocytes (PBLs) with different concentrations (0, 0.5, 1.25, 2.5, 3.75 and 5.0 μM) of this compound. The treatment of PBLs with carbofuran displayed significant DNA damage in concentration dependent manner. The carbofuran induced genotoxicity could be ameliorated to considerable extent by pretreatment of PBLs with equimolar (10 μM) concentration of each of the vitamins C and E; the magnitude of protection by vitamin E being higher than by vitamin C. Also, it was found that the level of protection by these vitamins was higher when PBLs were treated with lower concentrations of pesticide. The significant DNA damage as observed by H_{2}O_{2}, a positive control in the present study, and its amelioration by natural antioxidants (vitamins C and E) lend an evidence to suggest that carbofuran would have caused genotoxicity via pesticide induced oxidative stress.

  15. A study assessing the genotoxicity in rats after chronic oral exposure to a low dose of depleted uranium

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate the potential genotoxicity induced by chronic oral exposure to depleted uranium (DU). Weanling Wistar rats (F0), 50/sex/group, were exposed to DU in food at doses of 0, 4, or 40 mg kg-1 day-1 for four months. They were subsequently mated, resulting in the birth of F1 rats. Fifty F1 weanlings/sex/group were exposed for four months to the same dose levels as their parents. After four months, the uranium content in the tissues, the potential damage to the genetic material, and pathomorphological changes of the testicles were observed in both F0 and F1 rats. The genotoxicity of DU was evaluated by the following methods: sperm abnormality assessment, the bone-marrow micronucleus test, and the comet assay. Uranium content in F1 rats was significantly higher than that in F0 rats in both the kidney and ovary (p1 with F0 rats, significant differences were detected for most of the indicators, with F1 rats always exhibiting more damage (p1 rats. Genotoxicity may be induced in rats after chronic oral exposure to a low dose of DU. (author)

  16. What the Erythrocytic Nuclear Alteration Frequencies Could Tell Us about Genotoxicity and Macrophage Iron Storage?

    Science.gov (United States)

    Gomes, Juliana M. M.; Ribeiro, Heder J.; Procópio, Marcela S.; Alvarenga, Betânia M.; Castro, Antônio C. S.; Dutra, Walderez O.; da Silva, José B. B.; Corrêa Junior, José D.

    2015-01-01

    Erythrocytic nuclear alterations have been considered as an indicative of organism’s exposure to genotoxic agents. Due to their close relationship among their frequencies and DNA damages, they are considered excellent markers of exposure in eukaryotes. However, poor data has been found in literature concerning their genesis, differential occurrence and their life span. In this study, we use markers of cell viability; genotoxicity and cellular turn over in order to shed light to these events. Tilapia and their blood were exposed to cadmium in acute exposure and in vitro assays. They were analyzed using flow cytometry for oxidative stress and membrane disruption, optical microscopy for erythrocytic nuclear alteration, graphite furnace atomic absorption spectrometry for cadmium content in aquaria water, blood and cytochemical and analytical electron microscopy techniques for the hemocateretic aspects. The results showed a close relationship among the total nuclear alterations and cadmium content in the total blood and melanomacrophage centres area, mismatching reactive oxygen species and membrane damages. Moreover, nuclear alterations frequencies (vacuolated, condensed and blebbed) showed to be associated to cadmium exposure whereas others (lobed and bud) were associated to depuration period. Decrease on nuclear alterations frequencies was also associated with hemosiderin increase inside spleen and head kidney macrophages mainly during depurative processes. These data disclosure in temporal fashion the main processes that drive the nuclear alterations frequencies and their relationship with some cellular and systemic biomarkers. PMID:26619141

  17. Evaluation of cold shock-induced cytotoxicity and genotoxicity in the house fly Musca domestica

    Directory of Open Access Journals (Sweden)

    Nidhi Mishra

    2014-05-01

    Full Text Available Background: Low temperature affects the survival, growth and development of invertebrates, especially insects, based on the severity of cold and the duration of exposure. Although the effects of cold shock or direct chilling were previously analysed in terms of development patterns and defects, morphological changes, cold hardiness, cryopreservation and diapause in insects, very little information is available regarding the effects of cold shock at the chromosomal level. Material and Methods: Late third instar larvae of the house fly Musca domestica were exposed to low temperatures (10, 4, 0 and -5°C for different durations, in order to assess genotoxicity and cytotoxicity in the present study. The chromosomal aberration assay and micronucleus test were used as genotoxic end points. Cytotoxicity was evaluated by the mitotic index and the extent of tissue damage was observed using the Trypan blue staining method. Results: A significant (P<0.05, P<0.01 and P<0.001 increase in chromosome aberrations and micronucleus frequency was observed in all of the exposed groups compared to the control. The mitotic index showed a dose-dependent increase; however, it was lower in comparison to the control. The developmental patterns in exposed larvae exhibited an increase in larval mortality and a delay in adult emergence. Extensive tissue damage was observed at -5°C by Trypan blue staining. Conclusions: The present work suggests that cold shock induces chromosome aberrations and cytotoxicity and affects the developmental pattern in house fly, M. domestica.

  18. Protective effects of acerola juice on genotoxicity induced by iron in vivo

    Directory of Open Access Journals (Sweden)

    Roberta Nunes Horta

    2016-03-01

    Full Text Available Abstract Metal ions such as iron can induce DNA damage by inducing reactive oxygen species (ROS and oxidative stress. Vitamin C is one of the most widely consumed antioxidants worldwide, present in many fruits and vegetables, especially inMalpighia glabra L., popularly known as acerola, native to Brazil. Acerola is considered a functional fruit due to its high antioxidant properties and phenolic contents, and therefore is consumed to prevent diseases or as adjuvant in treatment strategies. Here, the influence of ripe and unripe acerola juices on iron genotoxicity was analyzed in vivo using the comet assay and micronucleus test. The comet assay results showed that acerola juice exerted no genotoxic or antigenotoxic activity. Neither ripe nor unripe acerola juices were mutagenic to animals treated with juices, in micronucleus test. However, when compared to iron group, the pre-treatment with acerola juices exerted antimutagenic activity, decreasing significantly micronucleus mean values in bone marrow. Stage of ripeness did not influence the interaction of acerola compounds with DNA, and both ripe and unripe acerola juices exerted protective effect over DNA damage generated by iron.

  19. In vitro genotoxicity of fipronil sister chromatid exchange, cytokinesis block micronucleus test, and comet assay.

    Science.gov (United States)

    Çelik, Ayla; Ekinci, Seda Yaprak; Güler, Gizem; Yildirim, Seda

    2014-03-01

    Fipronil (FP) is a phenylpyrazole pesticide developed by the transnational company Rhône-Poulenc Agro in 1987. Data on the genotoxicity and toxicity of FP are rather inadequate. In this study, we aimed to evaluate the potential genotoxic activity of FP using the single-cell microgel electrophoresis or comet assay, sister chromatid exchanges (SCEs), and micronuclei (MN) in human peripheral blood lymphocytes. In addition, the cytokinesis block proliferation index (CBPI) and proliferation index (PRI) were measured for cytotoxicity. In this study, three different doses of FP were used (0.7, 0.3, 0.1 μg/mL). Mitomycin C (2 μg/mL) and hydrogen peroxide were used as positive controls for SCE MN test systems, and comet assay, respectively. FP induced a statistically significant increase in the MN and SCE frequency and DNA damage in a dose-dependent manner in human peripheral blood lymphocytes (pcomet assay, we showed that all the doses of the FP induced DNA damage in human peripheral blood lymphocytes in vitro (p<0.05).

  20. ATM and ATR:Sensing DNA damage

    Institute of Scientific and Technical Information of China (English)

    Jun Yang; Zheng-Ping Xu; Yun Huang; Hope E. Hamrick; Penelope J. Duerksen-Hughes; Ying-Nian Yu

    2004-01-01

    Cellular response to genotoxic stress is a very complex process, and it usually starts with the "sensing" or "detection" of the DNA damage, followed by a series of events that include signal transduction and activation of transcription factors. The activated transcription factors induce expressions of many genes which are involved in cellular functions such as DNA repair, cell cycle arrest, and cell death. There have been extensive studies from multiple disciplines exploring the mechanisms of cellular genotoxic responses, which have resulted in the identification of many cellular components involved in this process, including the mitogen-activated protein kinases (MAPKs) cascade. Although the initial activation of protein kinase cascade is not fully understood,human protein kinases ATM (ataxia-telangiectasia, mutated) and ATR (ATM and Rad3-related) are emerging as potential sensors of DNA damage. Current progresses in ATM/ATR research and related signaling pathways are discussed in this review, in an effort to facilitate a better understanding of genotoxic stress response.

  1. Dietary elevated sucrose modulation of diesel-induced genotoxicity in the colon and liver of Big Blue rats

    DEFF Research Database (Denmark)

    Risom, L.; Moller, P.; Hansen, Max;

    2003-01-01

    . The mRNA expression levels of the DNA repair enzymes N-methylpurine DNA glycosylase (MPG), 8-oxoguanine DNA glycosylase (OGG1) and ERCC1 (part of the nucleotide excision repair complex) measured by reverse transcription-polymerase chain reaction were increased in liver by DEP feeding. In colon......Earlier studies have indicated that sucrose possesses either co-carcinogenic or tumor-promoter effects in colon carcinogenesis induced by genotoxic carcinogens. In this study we investigated the role of sucrose on diesel exhaust particle (DEP)-induced genotoxicity in the colonic mucosa and liver......-breaks and DNA adducts in liver. DEP and sucrose treatment did not have any effect on mutation frequency in colon and liver. Oxidative DNA damage detected as 8-oxodG (8-oxo-7,8-dihydro-2'-deoxyguanosine) and endonuclease III or formamidopyrimidine DNA glycosylase sensitive sites was unaltered in colon and liver...

  2. Effect ofBuchanania lanzan Spreng. bark extract on cyclophosphamide induced genotoxicity and oxidative stress in mice

    Institute of Scientific and Technical Information of China (English)

    Ritesh Jain; Sanmati Kumar Jain

    2012-01-01

    Objective:To elucidate the effect of ethanolic extract ofBuchanania lanzan Spreng. (B. lanan) bark against cyclophosphamide induced genotoxicity and oxidative stress in mice.Methods:The prevalence of micronuclei in bone marrow, the extent of lipid peroxidation, reduced glutathione and the status of the antioxidant enzymes, superoxide dismutase and catalase in liver of mice were used as intermediate biomarkers for chemoprotection. Lipid peroxidation and associated compromised antioxidant defenses in cyclophosphamide treated mice were observed in the liver.Results: Pre-treatment withB. lanzan250, 500 and1 000mg/ kg,p.o., daily for7 days significantly reduced the chromosomal damage and lipid peroxidation with concomitant changes in antioxidants and detoxification systems.Conclusions: These results point out the presence of chemopreventive phytoconstituents in the crude extract offering protection against cyclophosphamide induced genotoxicity and oxidative stress in mice.

  3. Anemia and genotoxicity induced by sub-chronic intragastric treatment of rats with titanium dioxide nanoparticles.

    Science.gov (United States)

    Grissa, Intissar; Elghoul, Jaber; Ezzi, Lobna; Chakroun, Sana; Kerkeni, Emna; Hassine, Mohsen; El Mir, Lassaad; Mehdi, Meriem; Ben Cheikh, Hassen; Haouas, Zohra

    2015-12-01

    Titanium dioxide nanoparticles (TiO2 NPs) are widely used for their whiteness and opacity. We investigated the hematological effects and genotoxicity of anatase TiO2 NPs following sub-chronic oral gavage treatment. TiO2-NPs were characterized by X-ray diffractometry (XRD), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). Wistar rats were treated with anatase TiO2 NPs by intragastric administration for 60 days. Hematological analysis showed a significant decrease in RBC and HCT and a significant increase in MCV, PLT, MPV and WBC at higher doses. Furthermore, abnormally shaped red cells, sometimes containing micronuclei, and hyper-segmented neutrophil nuclei were observed with TiO2 NPs treatment. The micronucleus test revealed damage to chromosomes in rat bone marrow at 100 and 200mg/kg bw; the comet assay showed significant DNA damage at the same doses.

  4. Genotoxic responses of juvenile tilapia (Oreochromis niloticus) exposed to florfenicol and oxytetracycline.

    Science.gov (United States)

    Botelho, R G; Christofoletti, C A; Correia, J E; Ansoar, Y; Olinda, R A; Tornisielo, V L

    2015-08-01

    Florfenicol (FLC) and oxytetracycline (OTC) are the two most commonly used antibiotics for bacterial treatment in fish farming in Brazil, and because of their intensive use, the potential harmful effects on aquatic organisms are of great concern. This study evaluated the effects of environmental concentrations of FLC and OTC on the genetic material of juvenile tilapia (Oreochromis niloticus) erythrocytes by using the comet assay and the occurrence of micronuclei (MN) and other erythrocytic nuclear abnormalities (ENAs) after exposure to 96hour. The comet assay showed that fish erythrocytes exhibited significantly higher DNA damage after exposure to environmental concentrations of FLC and OTC. Although MN was not observed, ENAs were significantly higher after exposure to FLC, indicating that ENAs are a better biomarker for FLC than MN. The results showed that environmental concentrations of FLC and OTC were genotoxic to erythrocytes of O. niloticus; however, future studies on DNA damage recovery are needed. PMID:25898970

  5. Application of the micronucleus test and comet assay in Trachemys callirostris erythrocytes as a model for in situ genotoxic monitoring.

    Science.gov (United States)

    Zapata, Lina M; Bock, Brian C; Orozco, Luz Yaneth; Palacio, Jaime A

    2016-05-01

    Trachemys callirostris is a turtle species endemic to northern South America. In northern Colombia it occurs in the middle and lower Magdalena River drainage and its principal tributaries (lower Cauca and San Jorge rivers) and in other minor drainages such as the lower Sinú River. In recent years, industrial, agricultural, and mining activities have altered natural habitats in Colombia where this species occurs, and many of the pollutants released there are known to induce genetic alterations in wildlife species. The micronucleus test and comet assay are two of the most widely used methods to characterize DNA damage induced by physical and chemical agents in wildlife species, but have not been employed previously for genotoxic evaluations in T. callirostris. The goal of this study was to optimize these genotoxic biomarkers for T. callirostris erythrocytes in order to establish levels of DNA damage in this species and thereby evaluate its potential as a sentinel species for monitoring genotoxic effects in freshwater environments in northern Colombia. Both genotoxic techniques were applied on peripheral blood erythrocytes from 20 captive-reared T. callirostris individuals as a negative control, as well as from samples obtained from 49 individuals collected in Magangué (Magdalena River drainage) and 24 individuals collected in Lorica (Sinú River drainage) in northern Colombia. Negative control individuals exhibited a baseline frequency of micronuclei of 0.78±0.58 and baseline values for comet tail length and tail moment of 3.34±0.24µm and 10.70±5.5, respectively. In contrast, samples from both field sites exhibited significantly greater evidence of genotoxic effects for both tests. The mean MN frequencies in the samples from Magangué and Lorica were 8.04±7.08 and 12.19±12.94, respectively. The mean tail length for samples from Magangué and Lorica were 5.78±3.18 and 15.46±7.39, respectively. Finally, the mean tail moment for samples from Magangué and

  6. The genotoxic effects of DNA lesions induced by artificial UV-radiation and sunlight.

    Science.gov (United States)

    Schuch, André Passaglia; Menck, Carlos Frederico Martins

    2010-06-01

    Solar radiation sustains and affects all life forms on Earth. The increase in solar UV-radiation at environmental levels, due to depletion of the stratospheric ozone layer, highlights serious issues of social concern. This becomes still more dramatic in tropical and subtropical regions where radiation-intensity is still higher. Thus, there is the need to evaluate the harmful effects of solar UV-radiation on the DNA molecule as a basis for assessing the risks involved for human health, biological productivity and ecosystems. In order to evaluate the profile of DNA damage induced by this form of radiation and its genotoxic effects, plasmid DNA samples were exposed to artificial-UV lamps and directly to sunlight. The induction of cyclobutane pyrimidine dimer photoproducts (CPDs) and oxidative DNA damage in these molecules were evaluated by means of specific DNA repair enzymes. On the other hand, the biological effects of such lesions were determined through the analysis of the DNA inactivation rate and mutation frequency, after replication of the damaged pCMUT vector in an Escherichia coliMBL50 strain. The results indicated the induction of a significant number of CPDs after exposure to increasing doses of UVC, UVB, UVA radiation and sunlight. Interestingly, these photoproducts are those lesions that better correlate with plasmid inactivation as well as mutagenesis, and the oxidative DNA damages induced present very low correlation with these effects. The results indicated that DNA photoproducts play the main role in the induction of genotoxic effects by artificial UV-radiation sources and sunlight.

  7. Comparison of the expression profiles induced by genotoxic and nongenotoxic carcinogens in rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Ellinger-Ziegelbauer, Heidrun [Bayer Healthcare AG, Department of Molecular and Genetic Toxicology, Aprather Weg 18a, 42096 Wuppertal (Germany)]. E-mail: heidrun.ellinger-ziegelbauer@bayerhealthcare.com; Stuart, Barry [Bayer Crop Science, Department of Toxicology, Stilwell, KS (United States); Wahle, Brad [Bayer Crop Science, Department of Toxicology, Stilwell, KS (United States); Bomann, Werner [Bayer Crop Science, Department of Toxicology, Stilwell, KS (United States); Ahr, Hans Juergen [Bayer Healthcare AG, Department of Molecular and Genetic Toxicology, Aprather Weg 18a, 42096 Wuppertal (Germany)

    2005-08-04

    Application of recently developed gene expression techniques using microarrays in toxicological studies (toxicogenomics) facilitate the interpretation of a toxic compound's mode of action and may also allow the prediction of selected toxic effects based on gene expression changes. In order to test this hypothesis, we investigated whether carcinogens at doses known to induce liver tumors in the 2-year rat bioassay deregulate characteristic sets of genes in a short term in vivo study and whether these deregulated genes represent defined biological pathways. Male Wistar rats were dosed with the four nongenotoxic hepatocarcinogens methapyrilene (MPy, 60 mg/kg/day), diethylstilbestrol (DES, 10 mg/kg/day), Wy-14643 (Wy, 60 mg/kg/day), and piperonylbutoxide (PBO, 1200 mg/kg/day). After 1, 3, 7, and 14 days, the livers were taken for histopathological evaluation and for analysis of the gene expression profiles on Affymetrix RG{sub U}34A arrays. The expression profile of the four nongenotoxic carcinogens were compared to the profiles of the four genotoxic carcinogens 2-nitrofluorene (2-NF), dimethylnitrosamine (DMN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and aflatoxin B1 (AB1) from a similar study reported previously. By using statistical and clustering tools characteristically deregulated genes were extracted and functionally classified. Distinct cellular pathways were affected by the nongenotoxic carcinogens compared to the genotoxic carcinogens which at least partly correlated with the two-stage model of carcinogenesis. Characteristic to genotoxic carcinogens were a DNA damage response and the activation of proliferative and survival signaling. Nongenotoxic carcinogens showed responses to oxidative DNA or protein damage, as well as cell cycle progression and signs of regeneration. Many of the gene alterations found with the nongenotoxic carcinogens imply compound-specific mechanisms. Although neither a single gene nor a single pathway will be

  8. Assessment of status of three water bodies in Serbia based on tissue metal and metalloid concentration (ICP-OES) and genotoxicity (comet assay).

    Science.gov (United States)

    Sunjog, Karolina; Kolarević, Stoimir; Kračun-Kolarević, Margareta; Višnjić-Jeftić, Željka; Skorić, Stefan; Gačić, Zoran; Lenhardt, Mirjana; Vasić, Nebojša; Vuković-Gačić, Branka

    2016-06-01

    Metals and metalloids are natural components of the biosphere, which are not produced per se by human beings, but whose form and distribution can be affected by human activities. Like all substances, they are a contaminant if present in excess compared to background levels and/or in a form that would not normally occur in the environment. Samples of liver, gills, gonads and muscle from European chub, Squalius cephalus, were analyzed for Al, As, B, Ba, Cr, Cu, Fe, Hg, Mn, Mo, Sr and Zn using inductively coupled plasma optical emission spectrometry (ICP-OES) to highlight the importance of tissue selection in monitoring research. The comet assay or single cell gel electrophoresis (SCGE) was selected as an in vivo genotoxicity assay, a rapid and sensitive method for measuring genotoxic effects in blood, liver and gills of the European chub. Microscopic images of comets were scored using Comet IV Computer Software (Perceptive Instruments, UK). The objective of our study was to investigate two reservoirs, Zlatar and Garasi, and one river, Pestan by: (i) determining and comparing metal and metalloid concentrations in sediment, water and tissues of European chub: liver, gills, muscle and gonads (ii) comparing these findings with genotoxicity of water expressed through DNA damage of fish tissues. A clear link between the level of metals in water, sediment and tissues and between metal and genotoxicity levels at examined sites was not found. This suggests that other xenobiotics (possibly the organic compounds), contribute to DNA damage. PMID:27016612

  9. Monitoring genotoxic exposure in uranium mines

    International Nuclear Information System (INIS)

    Recent data from deep uranium mines in Czechoslovakia indicated that miners are exposed to other mutagenic factors in addition to radon daughter products. Mycotoxins were identified as a possible source of mutagens in these mines. Mycotoxins were examined in 38 samples from mines and in throat swabs taken from 116 miners and 78 controls. The following mycotoxins were identified from mines samples: aflatoxins B1 and G1, citrinin, citreoviridin, mycophenolic acid, and sterigmatocystin. Some mold strains isolated from mines and throat swabs were investigated for mutagenic activity by the SOS chromotest and Salmonella assay with strains TA100 and TA98. Mutagenicity was observed, especially with metabolic activation in citro. These data suggest that mycotoxins produced by molds in uranium mines are a new genotoxic factor im uranium miners. 17 refs., 4 tabs

  10. Monitoring genotoxic exposure in uranium mines

    Energy Technology Data Exchange (ETDEWEB)

    Sram, R.J.; Vesela, D.; Vesely, D. [Institute of Experimental Medicine, Prague (Czech Republic)] [and others

    1993-10-01

    Recent data from deep uranium mines in Czechoslovakia indicated that miners are exposed to other mutagenic factors in addition to radon daughter products. Mycotoxins were identified as a possible source of mutagens in these mines. Mycotoxins were examined in 38 samples from mines and in throat swabs taken from 116 miners and 78 controls. The following mycotoxins were identified from mines samples: aflatoxins B{sub 1} and G1, citrinin, citreoviridin, mycophenolic acid, and sterigmatocystin. Some mold strains isolated from mines and throat swabs were investigated for mutagenic activity by the SOS chromotest and Salmonella assay with strains TA100 and TA98. Mutagenicity was observed, especially with metabolic activation in citro. These data suggest that mycotoxins produced by molds in uranium mines are a new genotoxic factor im uranium miners. 17 refs., 4 tabs.

  11. DNA Damage Caused By Pesticide-contaminated Soil

    Institute of Scientific and Technical Information of China (English)

    K.KRISHNAMURTHI; S. SARAVANA DEVI; T. CHAKRABARTI

    2006-01-01

    Objective To determine the DNA damaging potential and the genotoxicity of individual compounds in pesticide contaminated soil. Methods In the present study, DNA damaging potential of pesticide-contaminated soil and the genotoxicity of individual compounds present in the soil were assessed using fluorimetric analysis of DNA unwinding assay. Results The contaminated soil sample showed 79% (P<0.001) of DNA strand break, whereas technical grade of major carbaryl and α-naphthol constituents of the contaminated soil showed 64% (P<0.01) and 60% (P<0.02) damage respectively. Conclusion Our results indicate that the toxicity caused by contaminated soil is mainly due to carbaryl and α -napthol, which are the major constituents of the soil sample analyzed by GC-MS.

  12. Evaluation of protective effect of amifostine on dacarbazine induced genotoxicity

    OpenAIRE

    Etebari, M.; Jafarian-Dehkordi, A.; Lame, V.

    2015-01-01

    Anticancer therapy with alkylating agents has been used for many years. Dacarbazine (DTIC) as an alkylating agent is used alone or in combination with other chemotherapy drugs. In order to inhibit the formation of secondary cancers resulting from chemotherapy with DTIC, preventional strategies is necessary. The present study was undertaken to evaluate the genoprotective effect of amifostine on the genotoxic effects of DTIC in cell culture condition. To determine the optimum genotoxic concentr...

  13. Non—Genotoxic Carcinogens.Approaches to Their Rish Assessment

    Institute of Scientific and Technical Information of China (English)

    J.A.CASTRO; M.I.DiazGomez; 等

    1993-01-01

    Epidemiological studies support the idea that most human cancers are related to chemicals present in the human environment.In turn,chemicals are believed to cause cancer via either genotoxic or non-genotoxic mechanisms.There were described in literature several simple rapid and inexpensive short term ests to reasonably predict the genotoxic nature of chemicals but in contrast,there is no reliable test or battery of tests available to predict the carcinogenicity of non-genotoxic compounds and this poses a major problem to their rish assessment.In addition,there are conflictive opinions about rish assessment needs for both classes of carcinogens.Some workers elieve that for non-genotoxic carcinogens,thresholds for exposure can be drawn while others do not.In this review,the reasons behind both of these opinions and the present hypotheses about the mechanism of action of non-genotoxic carcinogens are described and analyzed in relation to future needs.

  14. Genotoxicity of carbon nanofibers: Are they potentially more or less dangerous than carbon nanotubes or asbestos?

    International Nuclear Information System (INIS)

    The production of carbon nanofibers and nanotubes (CNF/CNT) and their composite products is increasing globally. CNF are generating great interest in industrial sectors such as energy production and electronics, where alternative materials may have limited performance or are produced at a much higher cost. However, despite the increasing industrial use of carbon nanofibers, information on their potential adverse health effects is limited. In the current study, we examine the cytotoxic and genotoxic potential of carbon-based nanofibers (Pyrograf (registered) -III) and compare this material with the effects of asbestos fibers (crocidolite) or single-walled carbon nanotubes (SWCNT). The genotoxic effects in the lung fibroblast (V79) cell line were examined using two complementary assays: the comet assay and micronucleus (MN) test. In addition, we utilized fluorescence in situ hybridization to detect the chromatin pan-centromeric signals within the MN indicating their origin by aneugenic (chromosomal malsegregation) or clastogenic (chromosome breakage) mechanisms. Cytotoxicity tests revealed a concentration- and time-dependent loss of V79 cell viability after exposure to all tested materials in the following sequence: asbestos > CNF > SWCNT. Additionally, cellular uptake and generation of oxygen radicals was seen in the murine RAW264.7 macrophages following exposure to CNF or asbestos but not after administration of SWCNT. DNA damage and MN induction were found after exposure to all tested materials with the strongest effect seen for CNF. Finally, we demonstrated that CNF induced predominately centromere-positive MN in primary human small airway epithelial cells (SAEC) indicating aneugenic events. Further investigations are warranted to elucidate the possible mechanisms involved in CNF-induced genotoxicity.

  15. Genotoxicity of carbon nanofibers: are they potentially more or less dangerous than carbon nanotubes or asbestos?

    Science.gov (United States)

    Kisin, E. R.; Murray, A.R.; Sargent, L.; Lowry, D.; Chirila, M.; Siegrist, K.J.; Schwegler-Berry, D.; Leonard, S.; Castranova, V.; Fadeel, B.; Kagan, V.E.; Shvedova, A.A.

    2011-01-01

    The production of carbon nanofibers and nanotubes (CNF/CNT) and their composite products is increasing globally. CNF are generating great interest in industrial sectors such as energy production and electronics, where alternative materials may have limited performance or are produced at a much higher cost. However, despite the increasing industrial use of carbon nanofibers, information on their potential adverse health effects is limited. In the current study, we examine the cytotoxic and genotoxic potential of carbon-based nanofibers (Pyrograf®-III) and compare this material with the effects of asbestos fibers (crocidolite) or single-walled carbon nanotubes (SWCNT). The genotoxic effects in the lung fibroblast (V79) cell line were examined using two complementary assays: the comet assay and micronucleus (MN) test. In addition, we utilized fluorescence in situ hybridization to detect the chromatin pan-centromeric signals within the MN indicating their origin by aneugenic (chromosomal malsegregation) or clastogenic (chromosome breakage) mechanisms. Cytotoxicity tests revealed a concentration- and time-dependent loss of V79 cell viability after exposure to all tested materials in the following sequence: asbestos>CNF>SWCNT. Additionally, cellular uptake and generation of oxygen radicals was seen in the murine RAW264.7 macrophages following exposure to CNF or asbestos but not after administration of SWCNT. DNA damage and MN induction were found after exposure to all tested materials with the strongest effect seen for CNF. Finally, we demonstrated that CNF induced predominately centromere-positive MN in primary human small airway epithelial cells (SAEC) indicating aneugenic events. Further investigations are warranted to elucidate the possible mechanisms involved in CNF-induced genotoxicity. PMID:21310169

  16. Genotoxicity of agricultural soils in the vicinity of industrial area.

    Science.gov (United States)

    Ansari, Mohd Ikram; Malik, Abdul

    2009-03-17

    Soil samples from agricultural fields (cultivated) in the vicinity of industrial area of Ghaziabad City (India) were collected. In this city, wastewater coming from both industrial and domestic sources and without any treatment is used to irrigate the food crops. This practice has been polluting the soil and pollutants might reach the food chain. Gas chromatographic analysis show the presence of certain organochlorine (DDE, DDT, dieldrin, aldrin and endosulfan) and organophosphorus (dimethoate, malathion, methylparathion and chlorpyrifos) pesticides in soil samples. Samples were extracted using different solvents, i.e. methanol, chloroform, acetonitrile, hexane and acetone (all were HPLC-grade, SRL, India), and the extracts were assayed for genotoxic potential using Ames Salmonella/microsome test, DNA repair defective mutants and bacteriophage lambda systems. TA98 and TA100 were found to be the most sensitive strains to all the soil extracts tested. Methanol extracts exhibited a maximum mutagenicity with TA98 strain {540 (-S9) and 638 (+S9) revertants/g of soil} and 938 (-S9) and 1008 (+S9) revertants/g of soil with TA100 strain. The damage in the DNA repair defective mutants was found maximum with methanolic extract followed by acetonitrile, chloroform, hexane and acetone at the dose level of 40 microl/ml culture after 6h of treatment. The survival was 25, 30, 32, 33 and 35% in polA strain after 6h of treatment when tested with wastewater irrigated soil extracts of methanol, acetonitrile, chloroform, hexane and acetone, respectively. A significant decrease in the plaque forming units of bacteriophage lambda was also observed when treated with 40 microl of test samples. Present results showed that methanolic extracts of soil were more toxic than other soil extracts. The soil is accumulating a large number of pollutants due to wastewater irrigation and this practice of accumulation has an impact on soil health.

  17. Evaluation of smoking genotoxicity in Turkish young adults

    Science.gov (United States)

    Zamani, Ayse G.; Durakbasi-Dursun, H. Gul; Demirel, Sennur; Acar, Aynur

    2011-01-01

    BACKGROUND: For the past few decades, it has been widely known in developed countries that tobacco is dangerous, but it is still insufficiently realized how big these dangers really are. AIMS: To determine and evaluate micronuclei (MN) frequencies of young smokers and nonsmokers in three different tissues (peripheric blood lymphoctes, buccal mucosa, and exfoliative urothelial cells) at the same time. MATERIALS AND METHODS: MN assay was performed on buccal mucosa, urothelial cells, and peripheric blood lymphocyte samples obtained from 15 healthy male smokers (>5 pack-years) and 15 healthy male nonsmoker controls who had not been exposed to any known genotoxic agent. STATISTICAL ANALYSIS USED: The statistical differences between smoker and nonsmoker groups were calculated by using student t test. The differences between smoker-group tissues were compared by ANOVA. RESULTS: It was found that MN frequency (mean value ± standard deviation) in oral mucosa cells from smokers and controls were 1.20 ± 0.22% and 0.26 ± 0.10%; in urothelial exfoliative cells, 1.29 ± 0.28% and 0.12 ± 0.08%; in peripheric blood lymphocytes, 1.53 ± 0.23% and 0.38 ± 0.12%, respectively. The mean MN frequencies in buccal mucosa, urothelial exfoliative cells, and peripheric blood lymphocytes were significantly higher in smokers than in those of controls (P<0.05). All tissues were affected from smoking, but the most destructive effect was seen in urothelial cells of smokers (P<0.05). CONCLUSIONS: Our data showed that cigarette smoke is a DNA damage causitive agent on exfoliative buccal mucosa and urothelial cells and peripheric blood lymphocytes of young smokers, but it has most destructive effect on urothelial cells. PMID:21814336

  18. Genotoxicity Evaluation of Irrigative Wastewater from Shijiazhuang City in China.

    Directory of Open Access Journals (Sweden)

    Xuehui Liu

    Full Text Available In the present study, the wastewater sample collected from the Dongming discharging river in Shijiazhuang city was analysed using both chemical analysis and biological assays including the Salmonella mutagenicity test, micronucleus test and single-cell gel electrophoresis. Chemical analysis of the sample was performed using gas chromatography mass spectrometry and inductively coupled plasma mass spectrometry. The Salmonella mutagenicity test was performed on Salmonella typhimurium TA97, TA98, TA100 and TA102 strains with and without S9 mixture. The mice received the wastewater in natura through drinking water at concentrations of 25%, 50%, and 100%. One group of mice was exposed for 2 consecutive days, and the other group of mice was exposed for 15 consecutive days. To establish the levels of primary DNA damage, single-cell gel electrophoresis was performed on treated mouse liver cell. The concentrations of chromium and lead in the sample exceeded the national standard (GB20922-2007 by 0.78 and 0.43-fold, respectively. More than 30 organic compounds were detected, and some of the detected compounds were mutagens, carcinogens and environmental endocrine disrupters. A positive response for Salmonella typhimurium TA98 strain was observed. Mouse exposure via drinking water containing 50% and 100% of wastewater for 15 consecutive days caused a significant increase of MN frequencies in a dose-response manner. Mouse exposure via drinking water containing 50% and 100% of wastewater for 15 consecutive days caused a significant increase of the Olive tail moments in a dose-response manner. All the results indicated that the sample from the Dongming discharging river in Shijiazhuang city exhibited genotoxicity and might pose harmful effects on the local residents.

  19. Identification of early target genes of aflatoxin B1 in human hepatocytes, inter-individual variability and comparison with other genotoxic compounds.

    Science.gov (United States)

    Josse, Rozenn; Dumont, Julie; Fautrel, Alain; Robin, Marie-Anne; Guillouzo, André

    2012-01-15

    Gene expression profiling has recently emerged as a promising approach to identify early target genes and discriminate genotoxic carcinogens from non-genotoxic carcinogens and non-carcinogens. However, early gene changes induced by genotoxic compounds in human liver remain largely unknown. Primary human hepatocytes and differentiated HepaRG cells were exposed to aflatoxin B1 (AFB1) that induces DNA damage following enzyme-mediated bioactivation. Gene expression profile changes induced by a 24h exposure of these hepatocyte models to 0.05 and 0.25μM AFB1 were analyzed by using oligonucleotide pangenomic microarrays. The main altered signaling pathway was the p53 pathway and related functions such as cell cycle, apoptosis and DNA repair. Direct involvement of the p53 protein in response to AFB1 was verified by using siRNA directed against p53. Among the 83 well-annotated genes commonly modulated in two pools of three human hepatocyte populations and HepaRG cells, several genes were identified as altered by AFB1 for the first time. In addition, a subset of 10 AFB1-altered genes, selected upon basis of their function or tumor suppressor role, was tested in four human hepatocyte populations and in response to other chemicals. Although they exhibited large variable inter-donor fold-changes, several of these genes, particularly FHIT, BCAS3 and SMYD3, were found to be altered by various direct and other indirect genotoxic compounds and unaffected by non-genotoxic compounds. Overall, this comprehensive analysis of early gene expression changes induced by AFB1 in human hepatocytes identified a gene subset that included several genes representing potential biomarkers of genotoxic compounds. PMID:22100608

  20. DNA damage activates a spatially distinct late cytoplasmic cell-cycle checkpoint network controlled by MK2-mediated RNA stabilization

    DEFF Research Database (Denmark)

    Reinhardt, H Christian; Hasskamp, Pia; Schmedding, Ingolf;

    2010-01-01

    Following genotoxic stress, cells activate a complex kinase-based signaling network to arrest the cell cycle and initiate DNA repair. p53-defective tumor cells rewire their checkpoint response and become dependent on the p38/MK2 pathway for survival after DNA damage, despite a functional ATR-Chk1...... expression as part of the DNA damage response in cancer cells....

  1. Assessment of Cr(VI-induced cytotoxicity and genotoxicity using high content analysis.

    Directory of Open Access Journals (Sweden)

    Chad M Thompson

    Full Text Available Oral exposure to high concentrations of hexavalent chromium [Cr(VI] induces intestinal redox changes, villus cytotoxicity, crypt hyperplasia, and intestinal tumors in mice. To assess the effects of Cr(VI in a cell model relevant to the intestine, undifferentiated (proliferating and differentiated (confluent Caco-2 cells were treated with Cr(VI, hydrogen peroxide or rotenone for 2-24 hours. DNA damage was then assessed by nuclear staining intensity of 8-hydroxydeoxyguanosine (8-OHdG and phosphorylated histone variant H2AX (γ-H2AX measured by high content analysis methods. In undifferentiated Caco-2, all three chemicals increased 8-OHdG and γ-H2AX staining at cytotoxic concentrations, whereas only 8-OHdG was elevated at non-cytotoxic concentrations at 24 hr. Differentiated Caco-2 were more resistant to cytotoxicity and DNA damage than undifferentiated cells, and there were no changes in apoptotic markers p53 or annexin-V. However, Cr(VI induced a dose-dependent translocation of the unfolded protein response transcription factor ATF6 into the nucleus. Micronucleus (MN formation was assessed in CHO-K1 and A549 cell lines. Cr(VI increased MN frequency in CHO-K1 only at highly cytotoxic concentrations. Relative to the positive control Mitomycin-C, Cr(VI only slightly increased MN frequency in A549 at mildly cytotoxic concentrations. The results demonstrate that Cr(VI genotoxicity correlates with cytotoxic concentrations, and that H2AX phosphorylation occurs at higher concentrations than oxidative DNA damage in proliferating Caco-2 cells. The findings suggest that in vitro genotoxicity of Cr(VI is primarily oxidative in nature at low concentrations. Implications for in vivo intestinal toxicity of Cr(VI will be discussed.

  2. Extract of Lillium candidum L. Can Modulate the Genotoxicity of the Antibiotic Zeocin

    Directory of Open Access Journals (Sweden)

    Peter Bryant

    2011-12-01

    Full Text Available Lilium candidum L. extract (LE is well known in folk medicine for the treatment of burns, ulcers, inflammations and for healing wounds. This work aims to clarify whether the genotoxic potential of the radiomimetic antibiotic zeocin (Zeo could be modulated by LE. Our results indicate that LE exerts no cytotoxic, DNA-damaging and clastogenic activity in in Chlamydomonas reinhardtii, Pisum sativum L. and Hordeum vulgare L. test systems over a broad concentration range. Weak but statistically significant clastogenic effects due to the induction of micronuclei and chromosome aberrations have been observed in H. vulgare L. after treatment with 200 and 300 μg/mL LE. To discriminate protective from adverse action of LE different experimental designs have been used. Our results demonstrate that the treatment with mixtures of LE and Zeo causes an increase in the level of DNA damage, micronuclei and “metaphases with chromatid aberrations” (MwA. Clear evidence has been also obtained indicating that pretreatment with LE given 4 h before the treatment with Zeo accelerates the rejoining kinetics of Zeo-induced DNA damage in P. sativum L. and C. reinhardtii, and can decrease clastogenic effect of Zeo measured as frequencies of micronuclei and MwA in H. vulgare L. Here, we show for the first time that LE can modulate the genotoxic effects of zeocin. The molecular mode of action strongly depends on the experimental design and varies from synergistic to protective effect (adaptive response–AR. Our results also revealed that LE-induced AR to zeocin involves up-regulation of DSB rejoining in C. reinhardtii and P. sativum L. cells.

  3. Genotoxicity in child populations exposed to Polycyclic Aromatic Hydrocarbons (PAHs in the air from Tabasco, Mexico

    Directory of Open Access Journals (Sweden)

    Aldeco R. Gamboa

    2008-12-01

    Full Text Available The economy of the state of Tabasco is based on oil extraction. However, this imposes major effects to the environment and communities. Examples are the Polycyclic Aromatic Hydrocarbons (PAHs that may be found in the soil, water and sediment of the region. Their volatility makes them available to living beings and results in genotoxic activity. The purpose of this study was to quantify the levels of PAHs in the air at several points in the state, and to analyze their relationship with possible damage to DNA on local inhabitants. Single Cell Gel Electrophoresis Assay (Comet Assay was applied to peripheral blood lymphocytes of five groups of children between six and 15 years of age. PAH samples were analyzed following US/EPA TO-13-A method. Results indicated the presence in the air of most of the 16 PAHs considered as high priority by EPA, some of which have been reported with carcinogenic activity. Differences (p<0.05 were found between PAHs concentration in the gaseous component and in the particulate component of air samples, with the greatest values for the gaseous component. Greatest PAH concentrations were detected in areas with high oil extraction activities. Children groups from high oil activity areas presented genotoxic damage labeled from moderate to high according to DNA migration from nuclei (Tail Length: 14.2 - 42.14 mm and Tail/Head: 0.97 - 2.83 mm compared with control group (12.25 and 0.63 mm, respectively. The group with greatest cell damage was located in the area with the greatest oil activity. We conclude that the presence of PAHs in the air may represent a health risk to populations that are chronically exposed to them at high oil activity regions.

  4. Genotoxicity assessment of propyl thiosulfinate oxide, an organosulfur compound from Allium extract, intended to food active packaging.

    Science.gov (United States)

    Mellado-García, P; Maisanaba, S; Puerto, M; Llana-Ruiz-Cabello, M; Prieto, A I; Marcos, R; Pichardo, S; Cameán, A M

    2015-12-01

    Essential oils from onion (Allium cepa L.), garlic (Allium sativum L.), and their main components, such as propyl thiosulfinate oxide (PTSO) are being intended for active packaging with the purpose of maintaining and extending food product quality and shelf life. The present work aims to assess for the first time the potential mutagenicity/genotoxicity of PTSO (0-50 µM) using the following battery of genotoxicity tests: (1) the bacterial reverse-mutation assay in Salmonella typhimurium (Ames test, OECD 471); (2) the micronucleus test (OECD 487) (MN) and (3) the mouse lymphoma thymidine-kinase assay (OECD 476) (MLA) on L5178YTk(+/-), cells; and (4) the comet assay (with and without Endo III and FPG enzymes) on Caco-2 cells. The results revealed that PTSO was not mutagenic in the Ames test, however it was mutagenic in the MLA assay after 24 h of treatment (2.5-20 µM). The parent compound did not induce MN on mammalian cells; however, its metabolites (in the presence S9) produced positive results (from 15 µM). Data from the comet assay indicated that PTSO did not induce DNA breaks or oxidative DNA damage. Further in vivo genotoxicity tests are needed to confirm its safety before it is used as active additive in food packaging. PMID:26607106

  5. Genotoxicity assessment of propyl thiosulfinate oxide, an organosulfur compound from Allium extract, intended to food active packaging.

    Science.gov (United States)

    Mellado-García, P; Maisanaba, S; Puerto, M; Llana-Ruiz-Cabello, M; Prieto, A I; Marcos, R; Pichardo, S; Cameán, A M

    2015-12-01

    Essential oils from onion (Allium cepa L.), garlic (Allium sativum L.), and their main components, such as propyl thiosulfinate oxide (PTSO) are being intended for active packaging with the purpose of maintaining and extending food product quality and shelf life. The present work aims to assess for the first time the potential mutagenicity/genotoxicity of PTSO (0-50 µM) using the following battery of genotoxicity tests: (1) the bacterial reverse-mutation assay in Salmonella typhimurium (Ames test, OECD 471); (2) the micronucleus test (OECD 487) (MN) and (3) the mouse lymphoma thymidine-kinase assay (OECD 476) (MLA) on L5178YTk(+/-), cells; and (4) the comet assay (with and without Endo III and FPG enzymes) on Caco-2 cells. The results revealed that PTSO was not mutagenic in the Ames test, however it was mutagenic in the MLA assay after 24 h of treatment (2.5-20 µM). The parent compound did not induce MN on mammalian cells; however, its metabolites (in the presence S9) produced positive results (from 15 µM). Data from the comet assay indicated that PTSO did not induce DNA breaks or oxidative DNA damage. Further in vivo genotoxicity tests are needed to confirm its safety before it is used as active additive in food packaging.

  6. Genotoxicity test of propolis extract, mineral trioksida aggregat, and calcium hydroxide on fibroblast BHK-21 cell cultures

    Directory of Open Access Journals (Sweden)

    Ceples Dian Kartika W.P

    2015-03-01

    Full Text Available Background: Health industry has always used natural products as an alternative. Propolis, a natural antibiotic, is a resinous yellow brown or dark brown substance derived from honey bees (Apis mellifera. The main chemical compounds contained in propolis are flavonoids, phenolics and other various aromatic compounds. Flavonoids are well known plant compounds that have antibacterial, antifungal, antiviral, antioxidant and anti-inflammatory proprieties. Propolis is expected to be an alternative used for root canal treatment with lower toxicity compared to calcium hydroxide (Ca(OH2 . Over the last decade, a new material, mineral trioxide aggregate (MTA was developed, and has been used as the gold standard. All materials used in mouth should be biocompatible. The initial level of material biocompatibility evaluation involves toxicity and genotoxicity tests. Purpose: This research is aimed to conduct comparison test of genotoxicity effect of propolis extract, MTA and Ca(OH2 on fibroblast BHK-21 cell culture. Methods: This research was conducted with single-cell gel electrophoresis method. Results: The results indicate that propolis extract cannot cause DNA damage, while MTA can cause apoptosis and Ca(OH2 can cause neucrosis. Conclusion: It can be concluded that propolis extract has genotoxicity effect lower than MTA and Ca(OH2 , but MTA has lower effect on fibroblast BHK-21 cell culture.

  7. Molecular and structural changes induced by essential oils treatments in Vicia faba roots detected by genotoxicity testing.

    Science.gov (United States)

    Sturchio, Elena; Boccia, Priscilla; Zanellato, Miriam; Meconi, Claudia; Donnarumma, Lucia; Mercurio, Giuseppe; Mecozzi, Mauro

    2016-01-01

    Over the last few years, there has been an increased interest in exploiting allelopathy in organic agriculture. The aim of this investigation was to examine the effects of essential oil mixtures in order to establish their allelopathic use in agriculture. Two mixtures of essential oils consisting respectively of tea tree oil (TTO) and clove plus rosemary (C + R) oils were tested. Phytotoxicity and genotoxicity tests on the root meristems of Vicia faba minor were performed. A phytotoxic influence was particularly relevant for C + R mixture, while genotoxicity tests revealed significant results with both C + R oil mixture and TTO. Phenotypic analysis on Vicia faba minor primary roots following C + R oil mixture treatment resulted in callose production, an early symptom attributed to lipid peroxidation. The approach described in this study, based on genotoxicity bioassays, might identify specific DNA damage induced by essential oil treatments. These tests may represent a powerful method to evaluate potential adverse effects of different mixtures of essential oils that might be useful in alternative agriculture. Future studies are focusing on the positive synergism of more complex mixtures of essential oils in order to reduce concentrations of potentially toxic components while at the same time maintaining efficacy in antimicrobial and antifungal management. PMID:26914511

  8. Genotoxicity evaluation of metformin and glimepiride by micronucleus assay in exfoliated urothelial cells of type 2 diabetes mellitus patients.

    Science.gov (United States)

    Harishankar, M K; Logeshwaran, S; Sujeevan, S; Aruljothi, K N; Dannie, M A; Devi, A

    2015-09-01

    Micronucleus (MN) assay was performed on the exfoliated urothelial cells to detect the genotoxic effects of the anti-hyperglycemic drugs, metformin and glimepiride in T2DM patients and to use it as a biomarker for DNA damage by assessing the frequency of micronuclei in the exfoliated urothelial cells. A total of 201 subjects (147 T2DM patients & 54 Normal cases) were selected from diverse age groups (25-75 years) and the mean MN frequency was examined per 1000 cells in all the subjects. Relative to the control group (5.02 ± 1.01), an increased MN frequency was observed in females (26.15 ± 2.15) when compared to males (23.08 ± 2.09) in T2DM patients. Further analysis showed that there was a profound increase in the number of MN in the patients using metformin alone (23.02 ± 4.44), or combination of metformin & glimepiride (24.98 ± 2.87) than to the subjects using glimepiride alone (17.52 ± 3.28). It has been proven by this simple, reliable and non-invasive method that metformin has a potential role in causing genotoxicity and that the MN observed in exfoliated urothelial cells could be used as a reliable biomarker in monitoring the genotoxic risk of the anti-hyperglycemic drugs. PMID:26115598

  9. Patterns of scAAV vector insertion associated with oncogenic events in a mouse model for genotoxicity.

    Science.gov (United States)

    Rosas, Lucia E; Grieves, Jessica L; Zaraspe, Kimberly; La Perle, Krista Md; Fu, Haiyan; McCarty, Douglas M

    2012-11-01

    Recombinant adeno-associated virus (rAAV) vectors have gained an extensive record of safety and efficacy in animal models of human disease. Infrequent reports of genotoxicity have been limited to specific vectors associated with excess hepatocellular carcinomas (HCC) in mice. In order to understand potential mechanisms of genotoxicity, and identify patterns of insertion that could promote tumor formation, we compared a self-complementary AAV (scAAV) vector designed to promote insertional activation (scAAV-CBA-null) to a conventional scAAV-CMV-GFP vector. HCC-prone C3H/HeJ mice and severe combined immunodeficiency (SCID) mice were infected with vector plus secondary treatments including partial hepatectomy (HPX) and camptothecin (CPT) to determine the effects of cell cycling and DNA damage on tumor incidence. Infection with either vector led to a significant increase in HCC incidence in male C3H/HeJ mice. Partial HPX after infection reduced HCC incidence in the cytomegalovirus-green fluorescent protein (CMV-GFP)-infected mice, but not in the cognate chicken β-actin (CBA)-null infected group. Tumors from CBA-null infected, hepatectomized mice were more likely to contain significant levels of vector DNA than tumors from the corresponding CMV-GFP-infected group. Most CBA-null vector insertions recovered from tumors were associated with known proto-oncogenes or tumor suppressors. Specific patterns of insertion suggested read-through transcription, enhancer effects, and disruption of tumor suppressors as likely mechanisms for genotoxicity.

  10. GFP tracking transcriptional activity endogenous p53: vector construction and application in genotoxicity detection

    Institute of Scientific and Technical Information of China (English)

    ZENG Wei-sen; LUO Chen; XIE Wei-bing; CHEN Han-yuan

    2001-01-01

    To establish a sensitive.and specific system for genotoxicity detection in vivo. Methods: Endogenous p53 tracer vector p53RE was constructed by using green fluorescent protein (GFP) as a reporter to trace p53 transcriptional activity under the control of base SV40 early promoter. The tracer cells 3T3-REG were established by transfecting NIH3T3 cells with tracer vector and treated with ultraviolet, H202 and adriamycin to induce DNA damage and the subsequent endogenous p53 expression. The GFP expression and its green fluorescence in the tracer cells were observed and measured with fluorescent microscope and FACS. Results: The GFP expression increased rapidly after various treatment and reached the maximum 1 h later, and decreased gradually afterwards. FACS analysis showed that GFP expression in 3T3-REG tracer cells was consistent with the concentration of H202, while that in 3T3-SVG cells, which were transfected with control vector pSV-GFP, hardly increased in response to the treatment. Conclusion: GFP tracing p53 transcriptional activity is a sensitive and specific method for genotoxicity detection.

  11. Genotoxicity of food preservative sodium sorbate in human lymphocytes in vitro.

    Science.gov (United States)

    Mamur, Sevcan; Yüzbaşıoğlu, Deniz; Unal, Fatma; Aksoy, Hüseyin

    2012-10-01

    The genotoxic effects of antimicrobial food additive sodium sorbate (SS) was assessed by using chromosome aberrations (CAs), sister-chromatid exchanges (SCEs), and micronucleus (MN) in cultured human lymphocytes and comet assay in isolated human lymphocytes. Lymphocytes were treated with four concentrations (100, 200, 400 and 800 μg/ml) of SS as well as a negative (sterile distilled water) and a positive control (Mitomycin-C: MMC for cultured lymphocytes and H(2)O(2) for isolated lymphocytes). The result of this study indicated that SS increased the frequency of CAs at both 24 and 48 h period compared to control. When gaps were included, this increase was significant at 200, 400 and 800 μg/ml concentrations at 24 h and, at all concentrations at 48 h treatment time. When gaps were excluded, this increase was significant at only 800 μg/ml concentration at both 24 and 48 h treatments. In addition, SS increased SCEs/cell and MN frequency at 400 and 800 μg/ml concentrations at both 24 and 48 h compared to negative control. Furthermore, this additive caused DNA damage at all concentrations in isolated human lymphocytes after 1 h in vitro exposure. The present results show that SS is genotoxic to the human peripheral blood lymphocytes in vitro at the highest concentrations.

  12. Evaluation of genotoxic variations in plant model systems in a case of metal stressors.

    Science.gov (United States)

    Ackova, Darinka Gjorgieva; Kadifkova-Panovska, Tatjana; Andonovska, Katerina Bačeva; Stafilov, Trajče

    2016-01-01

    This study was designed to assess the effects of long term, high metal exposition (cadmium, lead, copper, nickel and zinc) on DNA damage in four plant model systems [Taraxacum officinale (Asteraceae), Matricaria recutita L. (Asteraceae), Robinia pseudoacacia L. (Fabaceae), and Urtica dioica (Urticaceae)]. DNA stability was investigated by a Random Amplified Polymorphic DNA (RAPD) technique. Agarose-gel electrophoresis revealed total of 37 bands with different molecular weights ranging from 1250 to 5000 bp. It generated distinctive polymorphism value of 72.97% (27 bands) total in four plant species investigated. The dendrogram constructed using NTSYSpc programme showed that there is grouping in separate clusters of the same plant model collected from two different areas (metal-exposed and control samples). The study concluded that the long term metal-exposing periods had genotoxic stress on macromolecules of plant model systems investigated and biomarkers used should be augmented for reliable estimates of genotoxicity after exposure of plants to metal stressors. PMID:26853058

  13. Genotoxic and Nongenotoxic Effects of Glycidyl Methacrylate on Human Lung Fibroblast Cells

    Institute of Scientific and Technical Information of China (English)

    XUE-JUN YIN; FU-DE FANG; JIAN-NING XU; CHANG-QI ZOU; FENG-SHENG HE

    2003-01-01

    To evaluate the genotoxic and nongenotoxic effects of short-term exposure to glycidyl mathacrylate (GMA) on human lung fibroblast cells (2BS cells) in vitro. Methods DNA strand breakage was determined by single cell gel electrophoresis, and DNA ladder formation assay and flow cytometric analysis were carried out to detect apoptic responses of cells to GMA exposure.The HPRT gene mutation assay was used to evaluate the mutagenicity, and the effect of GMA on gap junctional intercellular communication (GJIC) in the exposed cells was examined with the scrape loading/dye transfer technique. The ability of GMA to transform 2BS cells was also tested by an in vitro cell transformation assay. Results Exposure to GMA resulted in a dose-dependent increase in DNA strand breaks but not apoptic responses. GMA was also shown to significantly induce HPRT gene mutations and morphological transformation in 2BS cells in vitro. In contrast, GMA produced a concentration-dependent inhibition of GJIC. Conclusions GMA elicits both genotoxic and nongenotoxic effects on 2BS cells in vitro. The induction of DNA damage and gene mutations and inhibition of GJIC by GMA may casually contribute to GMA-induced cell transformation.

  14. Application of SOS umu-test for the detection of genotoxic volatile chemicals and air pollutants.

    Science.gov (United States)

    Ong, T M; Stewart, J; Wen, Y F; Whong, W Z

    1987-01-01

    The SOS umu-test has been used for the detection of DNA-damaging agents. In this system the plasmid pSK1002 carrying a fused gene umuC-lacZ was introduced into Salmonella typhimurium TA1535. The SOS function induced by genotoxic agents is detected by a colorimetric measurement of beta-galactosidase activity encoded by the lacZ gene, which is regulated by the Umu operon. This system was used with modifications to study the SOS function inducibility of volatile chemicals (propylene oxide, methyl bromide, and ethylene dibromide) and air pollutants (diesel emission, welding fumes, and cigarette smoke). Tester cells were exposed directly to the test material. The enzyme activity of the treated cells was measured according to the established procedure. Results of the study showed that all chemicals and pollutants tested induced SOS function in a dose-related manner. These results indicate that the SOS umu-test is potentially useful for the in situ detection of genotoxic agents in occupational settings.

  15. Benzophenone guttiferone A from Garcinia achachairu Rusby (Clusiaceae presents genotoxic effects in different cells of mice.

    Directory of Open Access Journals (Sweden)

    Peterson Menezes Terrazas

    Full Text Available Benzophenones from natural sources and those of synthetic analogues present several reports of potent biological properties, and Guttiferone A represents a promising medicinal natural compound with analgesic and gastroprotective profiles. Considering that there are no reports that assess the genetic toxicity of Guttiferone A, the present study was undertaken to investigate the genotoxic potential of this benzophenone isolated from seeds of Garcinia achachairu in terms of DNA damage in different cells of Swiss albino mice using the comet assay, and its clastogenic/aneugenic effects in bone marrow cells in vivo by the micronucleus test. Cytotoxicity was assessed by scoring polychromatic (PCE and normochromatic (NCE erythrocytes ratio. Guttiferone A was administered by oral gavage at doses of 15, 30 and 60 mg/kg. The results showed that Guttiferone A produced genotoxic effects in leukocytes, liver, bone marrow, brain and testicle cells and clastogenic/aneugenic effects in bone marrow erythrocytes of mice. The PCE/NCE ratio indicated no cytotoxicity. Since guttiferone A is harmful to the genetic material we suggest caution in its use by humans.

  16. Textile effluent induced genotoxic effects and oxidative stress in Clarias gariepinus.

    Science.gov (United States)

    Ayoola, S O; Bassey, B O; Alimba, C G; Ajani, E K

    2012-09-01

    Human and ecological disorder experienced in industrial settlements as a result of improper disposal of chemicals such as textile effluent calls for careful surveillance on the state of the environment. This study investigated the toxicity of textile effluent discharge using biochemical and cytogenetic responses to ascertain the acute and sub lethal effects on Clarias gariepinus. The 96 h LC50 of C. gariepinus exposed to the textile effluent was 8.203 ml L(-1). Fourteen day exposures to 1, 2, 4 and 6 ml L(-1) doses were conducted and several toxicological endpoints were evaluated. Sub lethal genotoxicity and biochemical study was also carried out for fourteen days. The genotoxicity studies utilized micronucleus test while the biochemical studies quantified serum anti-oxidant status Total Protein (TP), Catalase (CAT), Superoxide Dismutase (SOD) and Malondialdehyde (MDA) of the exposed fish. Toxicity factor indicates that the 96 h LC50 was significantly more toxic than the 24 h LC50 (p effluent at the tested concentrations induced micronucleus and nuclear abnormalities in the peripheral blood of exposed fish. Micronucleus, notch and binucleated cell formation were significant (p 0.05). The results obtained from this study showed that textile effluent increase cytogenetic damage and altered anti-oxidant status in C. gariepinus. Chemicals in the effluent can be bioaccumulated and biomagnified in the aquatic organism hence affecting man. PMID:24163963

  17. P53 alters the cytotoxicity and genotoxicity for oxidized graphene in human B-lymphoblastoid cells

    Science.gov (United States)

    Petibone, Dayton Matthew

    Widespread use of oxidized graphene nanomaterials in industry, medicine, and consumer products raises concern about potential adverse impacts on human health. The p53 tumor suppressor protein is crucial to maintaining cellular and genetic stability to prevent carcinogenesis. Here, we show that oxygen functionalized graphene (f-G) absorption and p53 functional status correlate with cytotoxicity and genotoxicity in human B-lymphoblastoid cells. Trends in f-G absorption by were dose-dependent. Cells with functional p53 exposed to f-G arrested in G0/G1 phase of the cell cycle, suppressed f-G induced reactive oxygen species (ROS), and had elevated apoptosis. While compared to p53 competent cells, the p53 deficient cells exposed to f-G accumulated in S-phase of the cell cycle, had elevated ROS levels, and evaded apoptosis. The f-G genotoxicity was evident as increased loss-of-heterozygosity mutants independent of p53 status, and structural chromosome damage in p53 deficient cells. These findings have broad implications for the safety and efficacy of oxidized graphene nanomaterials in industrial, consumer products and biomedical applications.

  18. Dynamically regulated sumoylation of HDAC2 controls p53 deacetylation and restricts apoptosis following genotoxic stress

    Institute of Scientific and Technical Information of China (English)

    André Brandl; Tobias Wagner; Katharina M. Uhlig; Shirley K. Knauer; Roland H. Stauber; Frauke Melchior; Günter Schneider; Thorsten Heinzel; Oliver H. Kr(a)mer

    2012-01-01

    Histone deacetylase 2 (HDAC2) is relevant for homeostasis and plays a critical role in gastrointestinal cancers.Here,we report that post-translational modification of endogenous HDAC2 with small ubiquitin-related modifier 1 (SUMO1) is a new regulatory switch for the tumor suppressor p53.Sumoylation of HDAC2 at lysine 462 allows binding of HDAC2 to p53.Moreover,sumoylated HDAC2 is a previously not recognized biologically relevant site-specific deacetylase for p53.Deacetylation of p53 at lysine 320 by sumoylated HDAC2 blocks recruitment of p53 into promoter-associated complexes and p53-dependent expression of genes for cell cycle control and apoptosis.Thereby,catalytically active sumoylated HDAC2 restricts p53 functions and attenuates DNA damage-induced apoptosis.Genotoxic stress evokes desumoylation of HDAC2,enabling p53-dependent gene expression,Our data show a new molecular mechanism involving a dynamically controlled HDAC2-sumoylation/p53-acetylation switch that regulates cell fate decisions following genotoxic stress.

  19. Chemopreventive effect of cactus Opuntia ficus indica on oxidative stress and genotoxicity of aflatoxin B1

    Directory of Open Access Journals (Sweden)

    Ben Mansour Hédi

    2011-10-01

    Full Text Available Abstract Background Aflatoxin B1 (AFB1 is potent hepatotoxic and hepatocarcinogenic agent. In aflatoxicosis, oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage. The aim of this work was to evaluate the hepatoprotective effect of cactus cladode extract (CCE on aflatoxin B1-induced liver damage in mice by measuring malondialdehyde (MDA level, the protein carbonyls generation and the heat shock proteins Hsp 70 and Hsp 27 expressions in liver. We also looked for an eventual protective effect against AFB1-induced genotoxicity as determined by chromosome aberrations test, SOS Chromotest and DNA fragmentation assay. We further evaluated the modulation of p53, bax and bcl2 protein expressions in liver. Methods Adult, healthy balbC (20-25 g male mice were pre-treated by intraperitonial administration of CCE (50 mg/Kg.b.w for 2 weeks. Control animals were treated 3 days a week for 4 weeks by intraperitonial administration of 250 μg/Kg.b.w AFB1. Animals treated by AFB1 and CCE were divided into two groups: the first group was administrated CCE 2 hours before each treatment with AFB1 3 days a week for 4 weeks. The second group was administrated without pre-treatment with CCE but this extract was administrated 24 hours after each treatment with AFB1 3 days a week for 4 weeks. Results Our results clearly showed that AFB1 induced significant alterations in oxidative stress markers. In addition, it has a genotoxic potential and it increased the expression of pro apoptotic proteins p53 and bax and decreased the expression of bcl2. The treatment of CCE before or after treatment with AFB1, showed (i a total reduction of AFB1 induced oxidative damage markers, (ii an anti-genotoxic effect resulting in an efficient prevention of chromosomal aberrations and DNA fragmentation compared to the group treated with AFB1 alone (iii restriction of the effect of AFB1 by differential modulation of the expression of p53 which

  20. Logical network of genotoxic stress-induced NF-kappaB signal transduction predicts putative target structures for therapeutic intervention strategies

    OpenAIRE

    Naumann, Michael

    2009-01-01

    Rainer Poltz1, Raimo Franke1,#, Katrin Schweitzer1, Steffen Klamt2, Ernst-Dieter Gilles2, Michael Naumann11Institute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg, Germany; 2Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany; #Present address: Department of Chemical Biology, Helmholtz Centre for Infection Research, Braunschweig, GermanyAbstract: Genotoxic stress is induced by a broad range of DNA-damaging agents and could lead to a ...

  1. Genotoxicity of Graphene in Escherichia coli

    Science.gov (United States)

    Sharma, Ananya

    Rapid advances in nanotechnology necessitate assessment of the safety of nanomaterials in the resulting products and applications. One key nanomaterial attracting much interest in many areas of science and technology is graphene. Graphene is a one atom thick carbon allotrope arranged in a two-dimensional honeycomb lattice. In addition to being extremely thin, graphene has several extraordinary physical properties such as its exceptional mechanical strength, thermal stability, and high electrical conductivity. Graphene itself is relatively chemically inert and therefore pristine graphene must undergo a process called functionalization, which is combination of chemical and physical treatments that change the properties of graphene, to make it chemically active. Functionalization of graphene is of crucial importance as the end application of graphene depends on proper functionalization. In the field of medicine, graphene is currently a nanomaterial of high interest for building biosensors, DNA transistors, and probes for cancer detection. Despite the promising applications of graphene in several areas of biomedicine, there have been only few studies in recent years that focus on evaluating cytotoxicity of graphene on cells, and almost no studies that investigate how graphene exposure affects cellular genetic material. Therefore, in this study we used a novel approach to evaluate the genotoxicity, i.e., the effects of graphene on DNA, using Escherichia coli as a prokaryotic model organism.

  2. Genotoxicity of drinking water from Chao Lake

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Q.; Jiao, Q.C. [Nanjing Univ. (China). Dept. of Biological Science and Technology; Huang, X.M.; Jiang, J.P.; Cui, S.Q.; Yao, G.H.; Jiang, Z.R.; Zhao, H.K.; Wang, N.Y. [Anhui Antiepidemic Station, Hefei (China)

    1999-02-01

    Genotoxic activity appears to originate primarily from reactions of chlorine with humic substances in the source waters. Comparisons of extracts of settled versus chlorinated water have confirmed that chlorinating during water treatment produces mutagenic activity in the mutagenicity tests. Present work on XAD-2 extracts of raw, chlorinated (treated), and settled water from the Chao Lake region of China has involved a battery of mutagenicity assays for various genetic endpoints: the Salmonella test, the sister-chromatid exchange (SCE) induction in Chinese hamster lung (CHL) cells, and the micronucleus (MN) induction in the peripheral blood erythrocytes of silver carp. Extracts of raw and treated water but not the settled water are mutagenic in the Salmonella assay. On the other hand, extracts of three water samples show activity in the SCE and MN assays, especially the raw and treated water. These data show that contamination and chlorinating contribute mutagens to drinking water and suggest that the mammalian assays may be more sensitive for detecting mutagenicity in aquatic environment than the Salmonella test.

  3. Effect of particle size and dispersion status on cytotoxicity and genotoxicity of zinc oxide in human bronchial epithelial cells.

    Science.gov (United States)

    Roszak, Joanna; Catalán, Julia; Järventaus, Hilkka; Lindberg, Hanna K; Suhonen, Satu; Vippola, Minnamari; Stępnik, Maciej; Norppa, Hannu

    2016-07-01

    Data available on the genotoxicity of zinc oxide (ZnO) nanoparticles (NPs) are controversial. Here, we examined the effects of particle size and dispersion status on the cytotoxicity and genotoxicity of nanosized and fine ZnO, in the presence and absence of bovine serum albumin (BSA; 0.06%) in human bronchial epithelial BEAS-2B cells. Dynamic light scattering analysis showed the most homogenous dispersions in water alone for nanosized ZnO and in water with BSA for fine ZnO. After a 48-h treatment, both types of ZnO were cytotoxic within a similar, narrow dose range (1.5-3.0μg/cm(2)) and induced micronuclei at a near toxic dose range (1.25-1.75μg/cm(2)), both with and without BSA. In the comet assay, nanosized ZnO (1.25-1.5μg/cm(2)), in the absence of BSA, caused a statistically significant increase in DNA damage after 3-h and 6-h treatments, while fine ZnO did not. Our findings may be explained by better uptake or faster intracellular dissolution of nanosized ZnO without BSA during short treatments (3-6h; the comet assay), with less differences between the two ZnO forms after longer treatments (>48h; the in vitro micronucleus test). As ZnO is genotoxic within a narrow dose range partly overlapping with cytotoxic doses, small experimental differences e.g. in the dispersion of ZnO particles may have a substantial effect on the genotoxicity of the nominal doses added to the cell culture. PMID:27402478

  4. Polyvinyl polypyrrolidone attenuates genotoxicity of silver nanoparticles synthesized via green route, tested in Lathyrus sativus L. root bioassay.

    Science.gov (United States)

    Panda, Kamal K; Achary, V Mohan M; Phaomie, Ganngam; Sahu, Hrushi K; Parinandi, Narasimham L; Panda, Brahma B

    2016-08-01

    The silver nanoparticles (AgNPs) were synthesized extracellularly from silver nitrate (AgNO3) using kernel extract from ripe mango Mengifera indica L. under four different reaction conditions of the synthesis media such as the (i) absence of the reducing agent, trisodium citrate (AgNPI), (ii) presence of the reducing agent (AgNPII), (iii) presence of the cleansing agent, polyvinyl polypyrrolidone, PVPP (AgNPIII), and (iv) presence of the capping agent, polyvinyl pyrrolidone, PVP (AgNPIV). The synthesis of the AgNPs was monitored by UV-vis spectrophotometry. The AgNPs were characterised by the energy-dispersive X-ray spectroscopy, transmission electron microscopy, X-ray diffraction, and small-angle X-ray scattering. Functional groups on the AgNPs were established by the Fourier transform infrared spectroscopy. The AgNPs (AgNPI, AgNPII, AgNPIII and AgNPIV) were spherical in shape with the diameters and size distribution-widths of 14.0±5.4, 19.2±6.6, 18.8±6.6 and 44.6±13.2nm, respectively. Genotoxicity of the AgNPs at concentrations ranging from 1 to 100mgL(-1) was determined by the Lathyrus sativus L. root bioassay and several endpoint assays including the generation of reactive oxygen species and cell death, lipid peroxidation, mitotic index, chromosome aberrations (CA), micronucleus formation (MN), and DNA damage as determined by the Comet assay. The dose-dependent induction of genotoxicity of the silver ion (Ag(+)) and AgNPs was in the order Ag(+)>AgNPII>AgNPI>AgNPIV>AgNPIII that corresponded with their relative potencies of induction of DNA damage and oxidative stress. Furthermore, the findings underscored the CA and MN endpoint-based genotoxicity assay which demonstrated the genotoxicity of AgNPs at concentrations (≤10mgL(-1)) lower than that (≥10mgL(-1)) tested in the Comet assay. This study demonstrated the protective action of PVPP against the genotoxicity of AgNPIII which was independent of the size of the AgNPs in the L. sativus L. root bioassay

  5. Genotoxic effect of gamma radiation in vivo rats as evaluated by comet assay and micronucleus assay

    International Nuclear Information System (INIS)

    DNA is one of the most critical site of damage induced by UV, gamma radiation and other the environmental chemical pollutants. Genotoxic evaluation of environmental agents is generally carried out using cytogenetic markers like chromosomal aberrations, sister chromatid exchanges and micronuclei formation. During the recent years Single Cell Gel Electrophoresis/Comet Assay, has emerged as one of the most powerful assays to detect DNA damage at molecular level in any eukaryotic cell. Present studies were undertaken to investigate the effect of gamma radiation at DNA and chromosomal level using comet assay and micronucleus test. Female Wistar rats were exposed to gamma radiation using 60Co Teletherapy machine; 0.125, 0.25, 0.5 and 1.0 Gy at a dose rate of 0.33 Gy/min. Blood and bone marrow samples were processed for comet assay using the standard protocol. Bone marrow cells from femur bone were also processed for micronucleus assay. Results of these studies indicated a dose dependent increase in DNA damage as indicated by increase in tail length (TL), tail moment (TM) and % DNA in tail (% DNA- T). Similarly, a dose dependent increase in the frequency of micronucleated polychromatic erythrocytes (mn-PCEs) was also observed. A good correlation between, DNA damage and the induction of micronucleated erythrocytes was observed. (author)

  6. genotoxicity of the pesticide dichlorvos and herbicide butachlor on rana zhenhaiensis tadpoles

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    genotoxicity of dichlorvos and butachlor on erythrocytes of rana zhenhaiensis tadpoles was investigated by the alkaline single-cell gel electrophoresis assay or comet assay.tadpoles were treated for 24 h in the laboratory with different concentrations of the testing agents,2.256,4.512,6.768,9.024,11.280 mg/l for dichlorvos and 0.292,0.584,0.876,1.168,1.460 mg/l for butachlor,to use the comet assay to test for the significance of dosage responsiveness to an increase in dna damage,as measured by the mean dna tail length-to-width ratio.the concentrations of 4.512 mg/l dichlorvos and 0.876 mg/l butachlor resulted in highly significant increases in dna damage of the tadpoles.there were linear correlations between the mean dna tail length-to-width ratio and the concentrations of the two test substances.our results showed that the two commonly used agricultural chemicals caused dose dependent dna damage of amphibians,and that comet assay might be a useful tool for measuring dna damage of tadpoles exposed in the field.

  7. Inhibition of TGFbeta1 Signaling Attenutates ATM Activity inResponse to Genotoxic Stress

    Energy Technology Data Exchange (ETDEWEB)

    Kirshner, Julia; Jobling, Michael F.; Pajares, Maria Jose; Ravani, Shraddha A.; Glick, Adam B.; Lavin, Martin J.; Koslov, Sergei; Shiloh, Yosef; Barcellos-Hoff, Mary Helen

    2006-09-15

    Ionizing radiation causes DNA damage that elicits a cellular program of damage control coordinated by the kinase activity of ataxia telangiectasia mutated protein (ATM). Transforming growth factor {beta}1 (TGF{beta}), which is activated by radiation, is a potent and pleiotropic mediator of physiological and pathological processes. Here we show that TGF{beta} inhibition impedes the canonical cellular DNA damage stress response. Irradiated Tgf{beta}1 null murine epithelial cells or human epithelial cells treated with a small molecule inhibitor of TGF{beta} type I receptor kinase exhibit decreased phosphorylation of Chk2, Rad17 and p53, reduced {gamma}H2AX radiation-induced foci, and increased radiosensitivity compared to TGF{beta} competent cells. We determined that loss of TGF{beta} signaling in epithelial cells truncated ATM autophosphorylation and significantly reduced its kinase activity, without affecting protein abundance. Addition of TGF{beta} restored functional ATM and downstream DNA damage responses. These data reveal a heretofore undetected critical link between the microenvironment and ATM that directs epithelial cell stress responses, cell fate and tissue integrity. Thus, TGF{beta}1, in addition to its role in homoeostatic growth control, plays a complex role in regulating responses to genotoxic stress, the failure of which would contribute to the development of cancer; conversely, inhibiting TGF{beta} may be used to advantage in cancer therapy.

  8. In vivo genotoxicity of furan in F344 rats at cancer bioassay doses

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Wei, E-mail: Wei.Ding@fda.hhs.gov [Division of Genetic and Molecular Toxicology, US FDA/National Center for Toxicological Research, Jefferson, AR 72079 (United States); Petibone, Dayton M. [Division of Genetic and Molecular Toxicology, US FDA/National Center for Toxicological Research, Jefferson, AR 72079 (United States); Latendresse, John R. [Toxicologic Pathology Associates, US FDA/National Center for Toxicological Research, Jefferson, AR 72079 (United States); Pearce, Mason G. [Division of Genetic and Molecular Toxicology, US FDA/National Center for Toxicological Research, Jefferson, AR 72079 (United States); Muskhelishvili, Levan; White, Gene A. [Toxicologic Pathology Associates, US FDA/National Center for Toxicological Research, Jefferson, AR 72079 (United States); Chang, Ching-Wei [Division of Personalized Nutrition and Medicine, US FDA/National Center for Toxicological Research, Jefferson, AR 72079 (United States); Mittelstaedt, Roberta A.; Shaddock, Joseph G.; McDaniel, Lea P. [Division of Genetic and Molecular Toxicology, US FDA/National Center for Toxicological Research, Jefferson, AR 72079 (United States); Doerge, Daniel R. [Division of Biochemical Toxicology, US FDA/National Center for Toxicological Research, Jefferson, AR 72079 (United States); Morris, Suzanne M.; Bishop, Michelle E.; Manjanatha, Mugimane G.; Aidoo, Anane; Heflich, Robert H. [Division of Genetic and Molecular Toxicology, US FDA/National Center for Toxicological Research, Jefferson, AR 72079 (United States)

    2012-06-01

    Furan, a potent rodent liver carcinogen, is found in many cooked food items and thus represents a human cancer risk. Mechanisms for furan carcinogenicity were investigated in male F344 rats using the in vivo Comet and micronucleus assays, combined with analysis of histopathological and gene expression changes. In addition, formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III (EndoIII)-sensitive DNA damage was monitored as a measure of oxidative DNA damage. Rats were treated by gavage on four consecutive days with 2, 4, and 8 mg/kg bw furan, doses that were tumorigenic in 2-year cancer bioassays, and with two higher doses, 12 and 16 mg/kg. Rats were killed 3 h after the last dose, a time established as producing maximum levels of DNA damage in livers of furan-treated rats. Liver Comet assays indicated that both DNA strand breaks and oxidized purines and pyrimidines increased in a near-linear dose-responsive fashion, with statistically significant increases detected at cancer bioassay doses. No DNA damage was detected in bone marrow, a non-target tissue for cancer, and peripheral blood micronucleus assays were negative. Histopathological evaluation of liver from furan-exposed animals produced evidence of inflammation, single-cell necrosis, apoptosis, and cell proliferation. In addition, genes related to apoptosis, cell-cycle checkpoints, and DNA-repair were expressed at a slightly lower level in the furan-treated livers. Although a mixed mode of action involving direct DNA binding cannot be ruled out, the data suggest that furan induces cancer in rat livers mainly through a secondary genotoxic mechanism involving oxidative stress, accompanied by inflammation, cell proliferation, and toxicity. -- Highlights: ► Furan is a potent rodent liver carcinogen and represents a human cancer risk. ► Furan induces DNA damage in rat liver at cancer bioassay doses. ► Furan induces oxidative stress, inflammation and cell proliferation in rat liver. ► Expression of

  9. Subchronic mycotoxicoses in Wistar rats: assessment of the in vivo and in vitro genotoxicity induced by fumonisins and aflatoxin B(1), and oxidative stress biomarkers status.

    Science.gov (United States)

    Theumer, M G; Cánepa, M C; López, A G; Mary, V S; Dambolena, J S; Rubinstein, H R

    2010-01-31

    Some evidence suggests that fumonisin B(1) (FB(1)), a worldwide toxic contaminant of grains produced by Fusarium verticillioides, exhibits an oxidative stress mediated genotoxicity. We studied the DNA damage (by the alkaline comet and the micronucleus tests) and biomarkers of cellular oxidative stress (malondialdehyde, MDA; catalase, CAT; and superoxide dismutase, SOD) in spleen mononuclear cells of male Wistar rats subchronically (90 days) fed on a control experimental diet (CED) or poisoned with experimental diets contaminated with a culture material containing 100 ppm of FB(1) (FED), with 40 ppb of aflatoxin B(1) (a common toxic co-contaminant in cereals, AFB(1)ED), and with a mixture of both toxins (MED). The DNA damage was found in 13.7%, 81.7%, 98.0% and 99.3% (comet assay) and in 2.8%, 7.0%, 10.8% and 8.8% (micronucleus technique) in groups CED, FED, AFB(1)ED and MED, respectively. The MDA levels as well as the CAT and SOD activities were increased in all the poisoned animals. A similar behavior was observed in cells exposed in vitro to the toxins. These data support the hypothesis of an oxidative stress mediated genotoxicity induced by FB(1). Furthermore, the extent of DNA damage assessed by the comet assay suggests a possible protective effect of the fumonisins-AFB(1) mixtures in vitro against the genotoxicity induced individually by the toxins.

  10. Red mud a byproduct of aluminum production contains soluble vanadium that causes genotoxic and cytotoxic effects in higher plants

    Energy Technology Data Exchange (ETDEWEB)

    Mišík, Miroslav [Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Burke, Ian T. [Earth Surface Science Institute, School of Earth and Environment, University of Leeds, Leeds LS2 9JT (United Kingdom); Reismüller, Matthias; Pichler, Clemens; Rainer, Bernhard [Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Mišíková, Katarina [Department of Botany, Faculty of Natural Sciences, Comenius University, Bratislava (Slovakia); Mayes, William M. [Centre for Environmental and Marine Sciences, University of Hull, Scarborough YO11 3AZ (United Kingdom); Knasmueller, Siegfried, E-mail: siegfried.knasmueller@meduniwien.ac.at [Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria)

    2014-09-15

    Red mud (RM) is a byproduct of aluminum production; worldwide between 70 and 120 million tons is produced annually. We analyzed RM which was released in the course of the Kolontar disaster in Hungary into the environment in acute and genotoxicity experiments with plants which are widely used for environmental monitoring. We detected induction of micronuclei which reflect chromosomal damage in tetrads of Tradescantia and in root cells of Allium as well as retardation of root growth with contaminated soils and leachates. Chemical analyses showed that RM contains metals, in particular high concentrations of vanadium. Follow-up experiments indicated that vanadate causes the effects in the plants. This compound causes also in humans DNA damage and positive results were obtained in carcinogenicity studies. Since it was found also in RM from other production sites our findings indicate that its release in the environment is a global problem which should be studied in more detail. Capsule abstract: Our findings indicate that the red mud causes genotoxic effect in plants probably due to the presence of vanadate which is contained at high concentrations in the residue. - Highlights: • Red mud, a by-product of aluminum production, causes DNA-damage in higher plants. • We showed that this effect is caused by vanadate a known carcinogenic genotoxin. • Vanadate is contained in high concentrations in the residue. • Release of red mud may cause adverse effects in ecosystems and affect human health.

  11. The application of the comet assay to assess the genotoxicity of environmental pollutants in the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Imanikia, Soudabeh; Galea, Francesca; Nagy, Eszter; Phillips, David H; Stürzenbaum, Stephen R; Arlt, Volker M

    2016-07-01

    This study aimed to establish a protocol for cell dissociation from the nematode Caenorhabditis elegans (C. elegans) to assess the genotoxicity of the environmental pollutant benzo[a]pyrene (BaP) using the alkaline version of the single cell electrophoresis assay (comet assay). BaP genotoxicity was assessed in C. elegans (wild-type [WT]; N2, Bristol) after 48h exposure (0-40μM). Induction of comets by BaP was concentration-dependent up to 20μM; comet% tail DNA was ∼30% at 20μM BaP and ∼10% in controls. Similarly, BaP-induced DNA damage was evaluated in C. elegans mutant strains deficient in DNA repair. In xpa-1 and apn-1 mutants BaP-induced comet formation was diminished to WT background levels suggesting that the damage formed by BaP that is detected in the comet assay is not recognised in cells deficient in nucleotide and base excision repair, respectively. In summary, our study provides a protocol to evaluate DNA damage of environmental pollutants in whole nematodes using the comet assay. PMID:27389785

  12. Studies on the genotoxicity of endosulfan in different tissues of fresh water fish Mystus vittatus using the comet assay.

    Science.gov (United States)

    Sharma, Shilpi; Nagpure, N S; Kumar, Ravindra; Pandey, Sanjay; Srivastava, Satish K; Singh, Poonam J; Mathur, P K

    2007-11-01

    Endosulfan, a widely used organochlorine pesticide, is readily bio-accumulative in fishes and can be indirectly harmful to human populations. Limited efforts have been made to study long-term genotoxic effects of endosulfan in different tissues of fish using gentoxicity biomarkers. Therefore, the current investigation was undertaken to detect single-cell DNA strand breaks induced by endosulfan in the fresh water teleost fish Mystus vittatus using the comet assay. The LC(50) value of technical grade endosulfan was first determined for the fish species in a semistatic system, and on the basis of the LC(50) value, the sublethal and nonlethal concentrations were determined. The DNA damage was measured in gill, kidney, and erythrocytes as the percentage of DNA in comet tails of fish specimens exposed to the sublethal and nonlethal concentrations of endosulfan. In general, significant effects (p < 0.01) from both concentration and time of exposure were observed in exposed fishes. It was found that all the tissues at all concentrations exhibited the highest DNA damage on day 1, after which there was a nonlinear decline in the percentage of tail DNA. The comparison of DNA damage among the tissues at different concentrations could not show the sensitivity of particular tissue to endosulfan. The current study explored the utility of the comet assay for in vivo laboratory studies using fish species to screen the genotoxic potential of chemical agents. PMID:17713809

  13. Red mud a byproduct of aluminum production contains soluble vanadium that causes genotoxic and cytotoxic effects in higher plants

    International Nuclear Information System (INIS)

    Red mud (RM) is a byproduct of aluminum production; worldwide between 70 and 120 million tons is produced annually. We analyzed RM which was released in the course of the Kolontar disaster in Hungary into the environment in acute and genotoxicity experiments with plants which are widely used for environmental monitoring. We detected induction of micronuclei which reflect chromosomal damage in tetrads of Tradescantia and in root cells of Allium as well as retardation of root growth with contaminated soils and leachates. Chemical analyses showed that RM contains metals, in particular high concentrations of vanadium. Follow-up experiments indicated that vanadate causes the effects in the plants. This compound causes also in humans DNA damage and positive results were obtained in carcinogenicity studies. Since it was found also in RM from other production sites our findings indicate that its release in the environment is a global problem which should be studied in more detail. Capsule abstract: Our findings indicate that the red mud causes genotoxic effect in plants probably due to the presence of vanadate which is contained at high concentrations in the residue. - Highlights: • Red mud, a by-product of aluminum production, causes DNA-damage in higher plants. • We showed that this effect is caused by vanadate a known carcinogenic genotoxin. • Vanadate is contained in high concentrations in the residue. • Release of red mud may cause adverse effects in ecosystems and affect human health

  14. Genotoxicity of Water Contaminants from the Basin of Lake Sevan, Armenia Evaluated by the Comet Assay in Gibel Carp (Carassius auratus gibelio) and Tradescantia Bioassays.

    Science.gov (United States)

    Simonyan, Anna; Gabrielyan, Barduch; Minasyan, Seyran; Hovhannisyan, Galina; Aroutiounian, Rouben

    2016-03-01

    Combination of bioassays and chemical analysis was applied to determine the genotoxic/mutagenic contamination in four different sites of the basin of Lake Sevan in Armenia. Water genotoxicity was evaluated using the single cell gel electrophoresis technique (comet assay) in erythrocytes of gibel carp (Carassius auratus gibelio), Tradescantia micronucleus (Trad-MCN) and Tradescantia stamen hair mutation (Trad-SHM) assays. Significant inter-site differences in the levels of water genotoxicity according to fish and Trad-MCN bioassays have been revealed. Two groups of locations with lower (south-southwest of the village Shorzha and Peninsula of Lake Sevan) and higher (estuaries of Gavaraget and Dzknaget rivers) levels of water genotoxicity were distinguished. Correlation analysis support the hypothesis that the observed genetic alterations in fish and plant may be a manifestation of the effects of water contamination by nitrate ions, Si, Al, Fe, Mn and Cu. Increase of DNA damage in fish also correlated with content of total phosphorus. PMID:26739952

  15. Genetic Damage Induced by Accidental Environmental Pollutants

    Directory of Open Access Journals (Sweden)

    Beatriz Pérez-Cadahía

    2006-01-01

    Full Text Available Petroleum is one of the main energy sources worldwide. Its transport is performed by big tankers following some established marine routes. In the last 50 years a total amount of 37 oil tankers have given rise to great spills in different parts of the world, Prestige being the last one. After the accident, a big human mobilisation took place in order to clean beaches, rocks and fauna, trying to reduce the environmental consequences of this serious catastrophe. These people were exposed to the complex mixture of compounds contained in the oil. This study aimed at determine the level of environmental exposure to volatile organic compounds (VOC, and the possible damage induced on the population involved in the different cleaning tasks by applying the genotoxicity tests sister chromatid exchanges (SCE, micronucleus (MN test, and comet assay. Four groups of individuals were included: volunteers (V, hired manual workers (MW, hired high-pressure cleaner workers (HPW and controls. The higher VOC levels were associated with V environment, followed by MW and lastly by HPW, probably due to the use of high-pressure cleaners. Oil exposure during the cleaning tasks has caused an increase in the genotoxic damage in individuals, the comet assay being the most sensitive biomarker to detect it. Sex, age and tobacco consumption have shown to influence the level of genetic damage, while the effect of using protective devices was less noticeable than expected, perhaps because the kind used was not the most adequate.

  16. Disperse Red 1 (textile dye) induces cytotoxic and genotoxic effects in mouse germ cells.

    Science.gov (United States)

    Fernandes, Fábio Henrique; Bustos-Obregon, Eduardo; Salvadori, Daisy Maria Fávero

    2015-06-01

    Disperse Red 1 (DR1), which is widely used in the textile industry, is an azo dye that contributes to the toxicity and pollution of wastewater. To assess the toxic effects of DR1 on reproduction, sexually mature male mice (Mus musculus, strain CF-1) were orally (gavage) treated with single doses of the compound at 20, 100 and 500 mg/kg body weight. Testicular features and sperm parameters were evaluated 8.3, 16.6 and 24.9 days after treatments. In addition to testicular toxicity caused by the dye, the data clearly showed an increased frequency of sperm with abnormal morphology and decreased fertility. An increased amount of DNA damage was also detected in testis cells 16.6 and 24.9 days after treatments with 100 and 500 mg/kg. This study demonstrated the toxic and genotoxic effects of DR1, indicating the harmful activity of this dye on reproductive health.

  17. Arsenic-Induced Genotoxicity and Genetic Susceptibility to Arsenic-Related Pathologies

    Directory of Open Access Journals (Sweden)

    Fabrizio Bianchi

    2013-04-01

    Full Text Available The arsenic (As exposure represents an important problem in many parts of the World. Indeed, it is estimated that over 100 million individuals are exposed to arsenic, mainly through a contamination of groundwaters. Chronic exposure to As is associated with adverse effects on human health such as cancers, cardiovascular diseases, neurological diseases and the rate of morbidity and mortality in populations exposed is alarming. The purpose of this review is to summarize the genotoxic effects of As in the cells as well as to discuss the importance of signaling and repair of arsenic-induced DNA damage. The current knowledge of specific polymorphisms in candidate genes that confer susceptibility to arsenic exposure is also reviewed. We also discuss the perspectives offered by the determination of biological markers of early effect on health, incorporating genetic polymorphisms, with biomarkers for exposure to better evaluate exposure-response clinical relationships as well as to develop novel preventative strategies for arsenic- health effects.

  18. Nucleo-cytoplasmic communication in apoptotic response to genotoxic and inflammatory stress

    Institute of Scientific and Technical Information of China (English)

    Jean Y. J. WANG

    2005-01-01

    Genotoxic agents or inflammatory cytokines activate cellular stress responses and trigger programmed cell death.We have identified a signal transduction module, including three nuclear proteins that participate in the regulation of cell death induced by chemotherapeutic agents and tumor necrosis factor (TNF). In this nuclear signaling module, retinoblastoma protein (Rb) functions as an inhibitor of apoptotic signal transduction. Inactivation of Rb by phosphorylation or caspase-dependent cleavage/degradation is required for cell death to occur. Rb inhibits the Abl tyrosine kinase. Thus,Rb inactivation is a pre-requisite for Abl activation by DNA damage or TNF. Activation of nuclear Abl and its downstream effector p73 induces mitochondriadependent cell death. The involvement of these nuclear signal transducers in TNF induced apoptosis, which does not require new gene expression, indicates that nuclear events other than transcription can contribute to extrinsic apoptotic signal transduction.

  19. Genotoxicity of processed food items and ready-to-eat snacks in Finland.

    Science.gov (United States)

    Omoruyi, Iyekhoetin Matthew; Pohjanvirta, Raimo

    2014-11-01

    Processed foods are an insufficiently characterized source of chemical mutagens for consumers. Here, we evaluated the genotoxicity of selected food products in Finland. Mutagenicity was determined by the standard plate incorporation assay followed by methylcellulose overlay and treat-and-wash assays, using the Salmonella strains TA 100 and 98 with and without metabolic activation. Generally, the mutagenic activity of food samples was low, but exhibited lot-wise variation. Cold cuts of cold-smoked beef, grilled turkey, and smoked chicken (a single batch of each) were mutagenic in all three assays with the TA 100 strain with and without metabolic activation, indicating the mutagenic effect was not secondary to histidine release from the food products. However, none of the food extracts showing mutagenic potential induced DNA damage in vitro using the Comet Assay. Our findings imply that in Finland today, there are still products the production methods of which should be refined to reduce the potential risk of mutagenicity to consumers.

  20. In vitro genotoxic evaluation of the medicinal plant Chenopodium ambrosioides L.

    Science.gov (United States)

    Gadano, A; Gurni, A; López, P; Ferraro, G; Carballo, M

    2002-06-01

    Chenopodium ambrosioides (Chenopodiaceae) is an anthelmintic herb used in Latin-America's folk medicine. The aim of this work is to evaluate genetic damage induced by decoction and infusion of this plant which were assayed in different concentrations (1, 10, 100, 1000 microg/ml), by addition of the extract to human lymphocyte cell cultures. The endpoints evaluated were chromosomal aberrations (CA), sister chromatid exchanges (SCE), cell proliferation kinetics (CPK) and mitotic indexes (MI). The repeated measure analysis of variance was used for statistic evaluation of the results. The results showed (a) a statistical increase in the percentage of cells with CA and in the frequency of SCE when cultures were exposed to both preparations of Paico, (b) a decrease in MI of both preparations assayed, although no modification in the CPK values either in the infusion or in the decoction was observed. These results suggest a possible genotoxic effect of both preparations, probably due to different active principles. PMID:12020922

  1. Mutagenic and genotoxic activities of four pesticides: captan, foltaf, phosphamidon and furadan.

    Science.gov (United States)

    Saxena, S; Ashok, B T; Musarrat, J

    1997-05-01

    The mutagenic and genotoxic potential of four pesticides viz. captan, foltaf, phosphamidon and furadan was evaluated by the Ames mutagenicity assay and their DNA damaging ability on radiation repair defective E. coli K-12 strains respectively. The mutagenic spectrum revealed captan to be most mutagenic in the absence of metabolic activation, while the presence of S9 mix led to an attenuated mutagenic response. Foltaf, phosphamidon and furadan were detected as relatively weaker mutagens. A significant decrease in the survival of SOS defective mutants, recA, lexA and pol- of E. coli was observed as compared to their wild-type counterparts in the presence of the pesticides. The role of SOS repair genes gains further support from the Salmonella strains triggering the error-prone SOS response.

  2. H2 O2-induced higher order chromatin degradation: A novel mechanism of oxidative genotoxicity

    Indian Academy of Sciences (India)

    Gregory W Konat

    2003-02-01

    The genotoxicity of reactive oxygen species (ROS) is well established. The underlying mechanism involves oxidation of DNA by ROS. However, we have recently shown that hydrogen peroxide (H2O2), the major mediator of oxidative stress, can also cause genomic damage indirectly. Thus, H2O2 at pathologically relevant concentrations rapidly induces higher order chromatin degradation (HOCD), i.e. enzymatic excision of chromatin loops and their oligomers at matrix-attachment regions. The activation of endonuclease that catalyzes HOCD is a signalling event triggered specifically by H2O2. The activation is not mediated by an influx of calcium ions, but resting concentrations of intracellular calcium ions are required for the maintenance of the endonuclease in an active form. Although H2O2-induced HOCD can efficiently dismantle the genome leading to cell death, under sublethal oxidative stress conditions H2O2-induced HOCD may be the major source of somatic mutations.

  3. Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells

    Directory of Open Access Journals (Sweden)

    Marina Pöttler

    2015-11-01

    Full Text Available Nanoparticles that are aimed at targeting cancer cells, but sparing healthy tissue provide an attractive platform of implementation for hyperthermia or as carriers of chemotherapeutics. According to the literature, diverse effects of nanoparticles relating to mammalian reproductive tissue are described. To address the impact of nanoparticles on cyto- and genotoxicity concerning the reproductive system, we examined the effect of superparamagnetic iron oxide nanoparticles (SPIONs on granulosa cells, which are very important for ovarian function and female fertility. Human granulosa cells (HLG-5 were treated with SPIONs, either coated with lauric acid (SEONLA only, or additionally with a protein corona of bovine serum albumin (BSA; SEONLA-BSA, or with dextran (SEONDEX. Both micronuclei testing and the detection of γH2A.X revealed no genotoxic effects of SEONLA-BSA, SEONDEX or SEONLA. Thus, it was demonstrated that different coatings of SPIONs improve biocompatibility, especially in terms of genotoxicity towards cells of the reproductive system.

  4. Evaluation of cytotoxicity and genotoxicity of some Philippine medicinal plants

    Directory of Open Access Journals (Sweden)

    Christine Chichioco-Hernandez

    2011-01-01

    Full Text Available The genotoxicity and toxicity of ethnomedicinal Philippine plants, which include Cassia fistula, Derris elliptica, Ficus elastica, Gliciridia sepium, Michelia alba, Morus alba, Pogostemon cablin and Ricinus communis, were tested using the Vitotox assay. The plants are used traditionally to treat several disorders like diabetes, weakness, menorrhagia, headache, toothache and rheumatism. The dried leaves were homogenized for overnight soaking in methanol at room temperature. The resulting alcoholic extracts were filtered and concentrated in vacuo and tested for their genotoxicity and cytotoxicity using Vitotox®. Results showed that the medicinal plants that were tested are not genotoxic nor cytotoxic, except for R. communis and P. cablin, which showed toxicity at high doses (low dilutions in the absence of S9.

  5. EVALUATION OF GENOTOXICITY AND CYTOTOXICITY OF TINOSPORA CORDIFOLIA (THUNB.

    Directory of Open Access Journals (Sweden)

    AMIT KUMAR

    2013-01-01

    Full Text Available The communication deals with the genotoxic and cytotoxic effects of commonly used medicinal plant, Tinosporacordifolia (Thunb.. Genotoxicity was studied using the Allium cepa L. root tip model using three dose concentrations(10, 20 and 30 mg/mL for 24, 48 and 72 h. T-test was performed to validate the significance of data. Datarevealed dose dependent alterations in the Mitotic Index (M.I.. The M.I. first showed a significant increase andthen reduced as the concentration of extract was raised. The extract increased the rate of growth in the A. ceparoot meristem cells. Moreover, no spindle disturbances, or micronuclei formation was observed indicating thatthe stem extract did not exhibit prominent genotoxic activity. Cytotoxicity of T. cordifolia extract was evaluatedusing RBCs. The extract showed significant dose dependent cytotoxic activity (p=2.98. Considering the aboveresults, the use of aqueous stem extract of Tinospora cordifolia can be considered safe at low dose.

  6. DNA Damage Response and Immune Defence: Links and Mechanisms

    Directory of Open Access Journals (Sweden)

    Björn Schumacher

    2016-08-01

    Full Text Available DNA damage plays a causal role in numerous human pathologies including cancer, premature aging and chronic inflammatory conditions. In response to genotoxic insults, the DNA damage response (DDR orchestrates DNA damage checkpoint activation and facilitates the removal of DNA lesions. The DDR can also arouse the immune system by for example inducing the expression of antimicrobial peptides as well as ligands for receptors found on immune cells. The activation of immune signalling is triggered by different components of the DDR including DNA damage sensors, transducer kinases, and effectors. In this review, we describe recent advances on the understanding of the role of DDR in activating immune signalling. We highlight evidence gained into (i which molecular and cellular pathways of DDR activate immune signalling, (ii how DNA damage drives chronic inflammation, and (iii how chronic inflammation causes DNA damage and pathology in humans.

  7. Genotoxic Effects in Swimmers Exposed to Disinfection By-products in Indoor Swimming Pools

    Science.gov (United States)

    Kogevinas, Manolis; Villanueva, Cristina M.; Font-Ribera, Laia; Liviac, Danae; Bustamante, Mariona; Espinoza, Felicidad; Nieuwenhuijsen, Mark J.; Espinosa, Aina; Fernandez, Pilar; DeMarini, David M.; Grimalt, Joan O.; Grummt, Tamara; Marcos, Ricard

    2010-01-01

    Background Exposure to disinfection by-products (DBPs) in drinking water has been associated with cancer risk. A recent study (Villanueva et al. 2007; Am J Epidemiol 165:148–156) found an increased bladder cancer risk among subjects attending swimming pools relative to those not attending. Objectives We evaluated adults who swam in chlorinated pools to determine whether exposure to DBPs in pool water is associated with biomarkers of genotoxicity. Methods We collected blood, urine, and exhaled air samples from 49 nonsmoking adult volunteers before and after they swam for 40 min in an indoor chlorinated pool. We estimated associations between the concentrations of four trihalomethanes (THMs) in exhaled breath and changes in micronuclei (MN) and DNA damage (comet assay) in peripheral blood lymphocytes before and 1 hr after swimming; urine mutagenicity (Ames assay) before and 2 hr after swimming; and MN in exfoliated urothelial cells before and 2 weeks after swimming. We also estimated associations and interactions with polymorphisms in genes related to DNA repair or to DBP metabolism. Results After swimming, the total concentration of the four THMs in exhaled breath was seven times higher than before swimming. The change in the frequency of micronucleated lymphocytes after swimming increased in association with higher exhaled concentrations of the brominated THMs (p = 0.03 for bromodichloromethane, p = 0.05 for chlorodibromomethane, p = 0.01 for bromoform) but not chloroform. Swimming was not associated with DNA damage detectable by the comet assay. Urine mutagenicity increased significantly after swimming, in association with the higher concentration of exhaled bromoform (p = 0.004). We found no significant associations with changes in micronucleated urothelial cells. Conclusions Our findings support potential genotoxic effects of exposure to DBPs from swimming pools. The positive health effects gained by swimming could be increased by reducing the potential health

  8. Variation in genotoxic stress tolerance among frog populations exposed to UV and pollutant gradients

    International Nuclear Information System (INIS)

    Populations of widely distributed species can be subjected to unequal selection pressures, producing differences in rates of local adaptation. We report a laboratory experiment testing tolerance variation to UV-B and polycyclic aromatic hydrocarbons (PAHs) among common frog (Rana temporaria) populations according to their natural exposure level in the field. Studied populations were naturally distributed along two gradients, i.e. UV-B radiation with altitude and level of contamination by PAHs with the distance to emitting sources (road traffic). Tadpoles from eight populations were subjected to (1) no or high level of artificial UV-B; (2) four concentrations of benzo[a]pyrene (BaP) (0, 50, 250, 500 μg L-1); (3) simultaneously to UV-B and BaP. Since both stressors are genotoxic, the number of micronucleated erythrocytes (MNE) in circulating red blood cells was used as a bioindicator of tadpole sensitivity. High-altitude populations appear to be locally adapted to better resist UV-B genotoxicity, as they showed the lowest MNE numbers. Conversely, no correlation was observed between levels of PAH contamination in the field and tadpole tolerance to BaP in the laboratory, indicating the absence of local adaptation for BaP tolerance in these populations. Nevertheless, the decrease of MNE formation due to BaP exposure with altitude suggests that high-altitude populations were intrinsically more resistant to BaP genotoxicity. We propose the hypothesis of a co-tolerance between UV-B and BaP in high-altitude common frog populations: local adaptation to prevent and/or repair DNA damage induced by UV-B could also protect these highland populations against DNA damage induced by BaP. The results of this study highlight the role of local adaptation along pollutant gradients leading to tolerance variation, which implies that is it necessary to take into account the history of exposure of each population and the existence of co-tolerance that can hide toxic effects of a new

  9. Evaluation of the genotoxic and mutagenic potentials of a living nosode compounded with Influenza A virus

    Directory of Open Access Journals (Sweden)

    Alvaro Leitao

    2011-09-01

    Full Text Available Background: The influenza virus has been responsible for contagious respiratory diseases with high mortality rates [1]. Some drugs have been used to treat human influenza. However, these drugs cause many common side effects and induce the appearance of resistant viral strains [2]. The impact caused by the influenza virus has motivated the development of new approaches for the prevention and control of influenza [3]. Therefore, a new homeopathic medicine was developed using, as a starting point, the infectious influenza virus [4]. This belongs to a group called living nosodes [5]. However, its mutagenic and genotoxic potentials, especially when used in low dilutions, has not yet been evaluated and it is important because this biotherapic is prepared from living microorganisms. Different methods can be used to detect mutagenic and genotoxicic effects. Aims: This study aims to evaluate the genotoxic and mutagenic potentials of influenza A living nosode at different homeopathic potencies. Methodology: 1 ml of purified viral suspension was diluted in 9 ml of sterile distilled water. This sample was submitted to 100 mechanical succussions (approximately 3 Hz, using Autic® Brazilian machine, originating the first dilution, named decimal (1x. 1 ml of this solution was diluted in 9 ml of solvent and was submitted to 100 sucussions, generating biotherapic 2x. This procedure was successively repeated, according to Brazilian Homeopathic Pharmacopoeia, to obtain the biotherapic 30x [6]. By the same technique, water vehicle was prepared until 30x potency to be used as control. All samples were prepared in sterile and under aseptic conditions, using laminar flow cabinet, class II, and were stored in the refrigerator (8ºC. The samples 1x, 6x, 12x, 18x, 24x and 30x and water 30x (vehicle control were analysed by: the Inductest, which assesses the ability of physical or chemical agents to promote lysogenic induction as a reflection of damage

  10. Evaluation of the genotoxic and mutagenic potentials of homeopathic Candida albicans solutions

    Directory of Open Access Journals (Sweden)

    André Luis Santos

    2011-09-01

    Full Text Available Background: Candida spp is naturally found in humans’ flora of skin, gastrointestinal and genitourinary tracts and, in general, up to 75% of the population does not have any symptom [1]. However, oral candidiasis is very common among HIV patients and patients undergoing chemotherapy. The treatment of oral candidiasis is necessary once the disease causes discomfort and dysphagia, resulting in poor nutrition, slow recovery, and prolonged hospital stay [2,3]. Preliminary results obtained by our group with a new biotherapic prepared from Candida albicans (Candida 30x showed a great potential to reduce the candida yeast adhesion rate when the epithelial cells were pre-treated. This study is currently being developed with the evaluation of mutagenic and genotoxic potentials of several homeopathic solutions. Aims: The goal of this study was to assess the genotoxic and mutagenic potentials of different homeopathic potencies of C. albicans. Methodology: One part of C. albicans yeast obtained from Brazilian patient’s blood [4] was diluted in 9 parts of sterile water. This sample was submitted to 100 mechanical succussions (approximately 3 Hz, using Autic® Brazilian machine, originating the first dilution (1x. Then, 1 ml of this solution was diluted in 9 ml of solvent, submitted to 100 succussions, obtaining 2x potency. This procedure was successively repeated to obtain 30x potency, according to Brazilian Homeopathic Pharmacopoeia [5]. By the same technique, water vehicle was prepared until 30x to be used as control. All samples were prepared in sterile and aseptic conditions, using laminar flow cabinet, class II and were stored in the refrigerator (8ºC. The samples 1x, 6x, 12x, 18x, 24x and 30x of C. albicans and water 30x (vehicle control were analysed by: the Inductest, which assesses the ability of physical or chemical agents to promote lysogenic induction as a reflection of damage in DNA

  11. Genotoxicity Assessment of Erythritol by Using Short-term Assay

    OpenAIRE

    Chung, Young-Shin; Lee, Michael

    2013-01-01

    Erythritol is a sugar alcohol that is widely used as a natural sugar substitute. Thus, the safety of its usage is very important. In the present study, short-term genotoxicity assays were conducted to evaluate the potential genotoxic effects of erythritol. According to the OECD test guidelines, the maximum test dose was 5,000 μg/plate in bacterial reverse mutation tests, 5,000 μg/ml in cell-based assays, and 5,000 mg/kg for in vivo testing. An Ames test did not reveal any positive results. No...

  12. EVALUATION OF GENOTOXICITY AND CYTOTOXICITY OF TINOSPORA CORDIFOLIA (THUNB.)

    OpenAIRE

    AMIT KUMAR; SUKUMAR DANDAPAT; MANOJ KUMAR; M. P. SINHA

    2013-01-01

    The communication deals with the genotoxic and cytotoxic effects of commonly used medicinal plant, Tinosporacordifolia (Thunb.). Genotoxicity was studied using the Allium cepa L. root tip model using three dose concentrations(10, 20 and 30 mg/mL) for 24, 48 and 72 h. T-test was performed to validate the significance of data. Datarevealed dose dependent alterations in the Mitotic Index (M.I.). The M.I. first showed a significant increase andthen reduced as the concentration of extract was rais...

  13. Genotoxic and tumorigenic pyrrolizidine alkaloids in Chinese herbal plants

    Institute of Scientific and Technical Information of China (English)

    P.P. Fu; Q. Xia; M.W. Chou; G. Lin

    2005-01-01

    Pyrrolizidine alkaloids are a class of hepatotoxic and tumorigenic compounds detected in Chinese herbal plants,contaminated foods, and dietary supplements. In this review, the sources, toxicity, genotoxicity, tumorigenicity, and the metabolic pathways,particular the activation pathways leading to hepatotoxicity and tumorigenicity, of pyrrolizidine alkaloids are briefly discussed, with a focus on the most recent important findings concerning the genotoxic mechanism by which riddelliine liver tumors. This mechanism involves the formation of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and may be general to most carcinogenic pyrrolizidine alkaloids.

  14. Genotoxicity evaluation of the herbicide Garlon(®) and its active ingredient (triclopyr) in fish (Anguilla anguilla L.) using the comet assay.

    Science.gov (United States)

    Guilherme, Sofia; Santos, Maria A; Gaivão, Isabel; Pacheco, Mário

    2015-09-01

    Triclopyr-based herbicides are broadly used worldwide for site preparation and forest vegetation management. Thus, following application, these agrochemicals can inadvertently reach the aquatic ecosystems. Garlon(®) is one of the most popular commercial denominations of this group of herbicides, considered as highly toxic to fish, even by its manufacturer. Although DNA is frequently regarded as a target of pesticide toxicity, the genotoxic potential of Garlon(®) to fish remains completely unknown. Hence, the main goal of this study was to evaluate the genotoxicity of Garlon(®) and its active ingredient (triclopyr), clarifying the underlying mechanisms. Therefore, the comet assay, implemented as the standard procedure, with an extra step involving DNA lesion-specific repair enzymes (formamidopyrimidine DNA glycosylase and endonuclease III), was used to identify DNA damage in blood cells of Anguilla anguilla L. Short-term exposures (1 and 3 days) to Garlon(®) and triclopyr were carried out, adopting environmentally realistic concentrations (67.6 and 270.5 µg L(-1) Garlon(®) and 30 and 120 µg L(-1) triclopyr). The results concerning the nonspecific DNA damage proved the risk of the herbicide Garlon(®) and its active ingredient triclopyr in both tested concentrations and exposure lengths. In addition, the higher genotoxic potential of the formulation, in comparison with the active ingredient, was demonstrated. When the additional breaks corresponding to net enzyme-sensitive sites were considered, none of the conditions revealed significant levels of oxidative damage. This identification of the genotoxic properties of triclopyr-based herbicides to fish highlights the need to develop less hazardous formulations, as well as the adoption of mitigation measures related to the application of these agrochemicals in the framework of forestry and agriculture sustainable management. PMID:24623388

  15. DNA damage induced by nitrous oxide: study in medical personnel of operating rooms.

    Science.gov (United States)

    Wrońska-Nofer, Teresa; Palus, Jadwiga; Krajewski, Wojciech; Jajte, Jolanta; Kucharska, Małgorzata; Stetkiewicz, Jan; Wasowicz, Wojciech; Rydzyński, Konrad

    2009-06-18

    Occupational exposure to anaesthetics such as nitrous oxide (N(2)O) and halogenated hydrocarbons has been suggested to increase risk of genetic damage. However, the dose-dependency of genotoxic effects has not been unequivocally established and their relation to occupational exposure limit (OEL) remain obscure. In this study, the genotoxicity associated with occupational exposure to anaesthetics has been investigated in a group of 55 female nurses and 29 male anaesthesiologists active for at least 5 years in a working environment containing variable concentrations of N(2)O and halogenated hydrocarbons. 83 unexposed health care workers (52 female nurses and 31 male doctors) matched for age, gender, smoking habit and employment duration were included in the control group. Genotoxicity has been assessed using comet test. Concentrations of nitrous oxide, sevoflurane and isoflurane monitored by gas chromatography and mass spectrometry made possible to relate the extent of DNA damage to the level of exposure. Our results for the first time document a positive correlation between the DNA damage and the N(2)O levels in the ambient air. By contrast, no correlation has been observed between genotoxic effects and concentrations of sevoflurane and isoflurane. The extent of genetic injury was especially aggravated among nurses and anaesthesiologists exposed to N(2)O in concentrations exceeding OEL (180 mg/m(3)). We conclude that occupational exposure to N(2)O is associated with increased DNA damage and that the level of exposure plays a critical role in this regard. PMID:19439331

  16. ATP-dependent chromatin remodeling in the DNA-damage response

    NARCIS (Netherlands)

    H. Lans (Hannes); J.A. Marteijn (Jurgen); W. Vermeulen (Wim)

    2012-01-01

    textabstractThe integrity of DNA is continuously challenged by metabolism-derived and environmental genotoxic agents that cause a variety of DNA lesions, including base alterations and breaks. DNA damage interferes with vital processes such as transcription and replication, and if not repaired prope

  17. Fungicide prochloraz induces oxidative stress and DNA damage in vitro.

    Science.gov (United States)

    Lundqvist, J; Hellman, B; Oskarsson, A

    2016-05-01

    Prochloraz is widely used in horticulture and agriculture, e.g. as a post-harvest anti-mold treatment. Prochloraz is a known endocrine disruptor causing developmental toxicity with multiple mechanisms of action. However, data are scarce concerning other toxic effects. Since oxidative stress response, with formation of reactive oxygen species (ROS), is a common mechanism for different toxic endpoints, e.g. genotoxicity, carcinogenicity and teratogenicity, the aim of this study was to investigate if prochloraz can induce oxidative stress and/or DNA damage in human cells. A cell culture based in vitro model was used to study oxidative stress response by prochloraz, as measured by the activity of the nuclear factor erythroid 2-related factor 2 (Nrf2), a key molecule in oxidative defense mechanisms. It was observed that prochloraz induced oxidative stress in cultured human adrenocortical H295R and hepatoma HepG2 cells at non-toxic concentrations. Further, we used Comet assay to investigate the DNA damaging potential of prochloraz, and found that non-toxic concentrations of prochloraz induced DNA damage in HepG2 cells. These are novel findings, contradicting previous studies in the field of prochloraz and genotoxicity. This study reports a new mechanism by which prochloraz may exert toxicity. Our findings suggest that prochloraz might have genotoxic properties. PMID:26945613

  18. Cordyceps sinensis: Genotoxic Potential in Human Peripheral Blood Cells and Antigenotoxic Properties Against Hydrogen Peroxide by Comet Assay.

    Science.gov (United States)

    Vasiljevic, Jovana D; Zivkovic, Lada P; Cabarkapa, Andrea M; Bajic, Vladan P; Djelic, Ninoslav J; Spremo-Potparevic, Biljana M

    2016-06-01

    Context • Cordyceps sinensis (C sinensis) is a well-known, traditional, Chinese medicinal mushroom, valued for its beneficial properties for human health. C sinensis has been reported to have immunomodulatory, anticancer, antiaging, antioxidant and anti-inflammatory activity. Despite potential medicinal benefits, no previously published reports are available about the genotoxicity or antigenotoxicity of C sinensis, as detected by comet assay. Objective • The objective of the study was to evaluate both the genotoxic and antigenotoxic potential of an extract of C sinensis (CS extract) in human peripheral blood cells. Design • The research team designed a pilot study. Setting •The study was conducted at the Center for Biological Research, University of Belgrade, in Belgrade, Serbia. Participants • Participants were 6 healthy individuals (2 males and 4 females), between the ages of 20 and 45 y, recruited on a voluntary basis, who provided heparinized, peripheral blood samples. Intervention • Four concentrations of the CS extract-125 μg/mL, 250 μg/mL, 500 μg/mL, and 1000 μg/mL-were used in the treatment of tested blood cells from the blood samples. Three independent procedures were performed: (1) a genotoxicity assessment, (2) an antigenotoxicity assessment for pretreatment of human cells with the CS extract prior to their exposure to hydrogen peroxide (H2O2) (ie, an evaluation of the benefits of the CS extract as a preventive agent); and (3) posttreatment of human cells with the CS extract after their exposure to H2O2 (ie, an evaluation of the benefits of the CS extract as an interventional agent). Outcome Measures • Cells were graded by eye inspection into 5 classes, depending on the extent of DNA damage, representing: (1) class A-undamaged cells with no tail (95%).Results • The CS extract proved to be nongenotoxic because no induced DNA damage was detected at all tested concentrations. For the antigenotoxicity assessment of the pretreatment with

  19. Combination of physico-chemical analysis, Allium cepa test system and Oreochromis niloticus erythrocyte based comet assay/nuclear abnormalities tests for cyto-genotoxicity assessments of treated effluents discharged from textile industries.

    Science.gov (United States)

    Hemachandra, Chamini K; Pathiratne, Asoka

    2016-09-01

    Bioassays for cyto-genotoxicity assessments are generally not required in current textile industry effluent discharge management regulations. The present study applied in vivo plant and fish based toxicity tests viz. Allium cepa test system and Oreochromis niloticus erythrocyte based comet assay and nuclear abnormalities tests in combination with physico-chemical analysis for assessing potential cytotoxic/genotoxic impacts of treated textile industry effluents reaching a major river (Kelani River) in Sri Lanka. Of the treated effluents tested from two textile industries, color in the Textile industry 1 effluents occasionally and color, biochemical oxygen demand and chemical oxygen demand in the Textile industry 2 effluents frequently exceeded the specified Sri Lankan tolerance limits for discharge of industrial effluents into inland surface waters. Exposure of A. cepa bulbs to 100% and 12.5% treated effluents from both industries resulted in statistically significant root growth retardation, mito-depression, and induction of chromosomal abnormalities in root meristematic cells in comparison to the dilution water in all cases demonstrating cyto-genotoxicity associated with the treated effluents. Exposure of O. niloticus to the 100% and 12.5% effluents, resulted in erythrocytic genetic damage as shown by elevated total comet scores and induction of nuclear abnormalities confirming the genotoxicity of the treated effluents even with 1:8 dilution. The results provide strong scientific evidence for the crucial necessity of incorporating cyto-genotoxicity impact assessment tools in textile industry effluent management regulations considering human health and ecological health of the receiving water course under chronic exposure.

  20. SIGNALING TO THE P53 TUMOR SUPPRESSOR THROUGH PATHWAYS ACTIVATED BY GENOTOXIC AND NON-GENOTOXIC STRESSES.

    Energy Technology Data Exchange (ETDEWEB)

    ANDERSON,C.W.APPELLA,E.

    2002-07-01

    The p53 tumor suppressor is a tetrameric transcription factor that is post-translational modified at {approx}18 different sites by phosphorylation, acetylation, or sumoylation in response to various cellular stress conditions. Specific posttranslational modifications, or groups of modifications, that result from the activation of different stress-induced signaling pathways are thought to modulate p53 activity to regulate cell fate by inducing cell cycle arrest, apoptosis, or cellular senescence. Here we review the posttranslational modifications to p53 and the pathways that produce them in response to both genotoxic and non-genotoxic stresses.

  1. Genotoxicity of low dose N-nitroso propoxur to human gastric cells.

    Science.gov (United States)

    Kuo, H H; Shyu, S S; Wang, T C

    2008-05-01

    Propoxur is among the most popular insect control agents in subtropical countries such as Taiwan. As a member of the N-methylcarbamate insecticide group, propoxur is notorious for its potential for conversion into highly genotoxic N-nitroso derivatives. Due to the fact that the stomach has been identified as the major target for N-nitroso N-methylcarbamates, this investigation used a human gastric cell line, SC-M1, in order to obtain results pertinent to the authentic adverse effects of this compound on human health. This report reveals that at dose levels inhibiting propoxur induced significant amounts of DNA damage. Most of the damaged DNA was repaired within 24 h after treatment removal, such that an outcome with a significant induction of chromosomal aberrations was not observed. Gene mutations and anchorage independence, on the other hand, were significantly induced by this same treatment. In conclusion, exposure to low doses of N-nitroso propoxur is not cytotoxic nor clastogenic, nevertheless, has the potential to increase genetic instability and, possibly as a result, to enhance the malignant potential of treated cells. We suggest that although the damaged DNA was repaired during the transient G2/M arrest period, it was probably not done in an appropriate way which would preserve the original genetic stability.

  2. In vivo and in vitro exposures for the evaluation of the genotoxic effects of lead on the Neotropical freshwater fish Prochilodus lineatus.

    Science.gov (United States)

    Monteiro, V; Cavalcante, D G S M; Viléla, M B F A; Sofia, S H; Martinez, C B R

    2011-08-01

    In the present study, in vivo and in vitro exposures were used to assess the genotoxicity of lead (Pb) to the freshwater fish Prochilodus lineatus. The comet assay using blood, liver and gill cells, and the occurrence of micronuclei (MN) and other erythrocytic nuclear abnormalities (ENA) were used to assess the genotoxic potential of lead in vivo. Metallothionein content (MT) was measured in fish liver in order to evaluate the protection of fish against Pb toxicity. Fish erythrocytes were exposed to Pb in vitro (1, 3 and 6 h) and the number of viable cells, DNA integrity, using the comet assay, and lysosomal membrane stability, measured by the neutral red retention assay (NRRA) were analyzed. The results of the comet assay after in vivo toxicity tests (6, 24 and 96 h) showed that Pb was genotoxic for all the three tissues analyzed after 96 h exposure. A significant increase in liver MT content was observed after 6 and 24 h of Pb exposure. MN frequency did not increase after Pb exposures, but the frequency of the other ENA, such as kidney-shaped nuclei, segmented nuclei and lobed nuclei, showed a significant increase after 24 and 96 h, indicating that ENA is a better biomarker for Pb exposure than MN alone after short-term exposures. The results of the comet assay performed with erythrocytes in vitro exposed to lead confirmed its genotoxic effect and showed that DNA damage increased with increasing exposure time. Moreover, the NRRA clearly indicated that Pb induces a destabilization of the lysosomal membrane. These results demonstrate the potential genotoxicity and cytotoxicity of lead after acute exposures.

  3. In vivo and in vitro exposures for the evaluation of the genotoxic effects of lead on the Neotropical freshwater fish Prochilodus lineatus

    Energy Technology Data Exchange (ETDEWEB)

    Monteiro, V.; Cavalcante, D.G.S.M.; Vilela, M.B.F.A. [Laboratory of Animal Ecophysiology, Department of Physiological Sciences, Londrina State University, PB 6001, 86051-990 Londrina, PR (Brazil); Sofia, S.H. [Laboratory of Genetics and Animal Ecology, Department of General Biology, Londrina State University, PB 6001, 86051-990 Londrina, PR (Brazil); Martinez, C.B.R., E-mail: cbueno@uel.br [Laboratory of Animal Ecophysiology, Department of Physiological Sciences, Londrina State University, PB 6001, 86051-990 Londrina, PR (Brazil)

    2011-08-15

    In the present study, in vivo and in vitro exposures were used to assess the genotoxicity of lead (Pb) to the freshwater fish Prochilodus lineatus. The comet assay using blood, liver and gill cells, and the occurrence of micronuclei (MN) and other erythrocytic nuclear abnormalities (ENA) were used to assess the genotoxic potential of lead in vivo. Metallothionein content (MT) was measured in fish liver in order to evaluate the protection of fish against Pb toxicity. Fish erythrocytes were exposed to Pb in vitro (1, 3 and 6 h) and the number of viable cells, DNA integrity, using the comet assay, and lysosomal membrane stability, measured by the neutral red retention assay (NRRA) were analyzed. The results of the comet assay after in vivo toxicity tests (6, 24 and 96 h) showed that Pb was genotoxic for all the three tissues analyzed after 96 h exposure. A significant increase in liver MT content was observed after 6 and 24 h of Pb exposure. MN frequency did not increase after Pb exposures, but the frequency of the other ENA, such as kidney-shaped nuclei, segmented nuclei and lobed nuclei, showed a significant increase after 24 and 96 h, indicating that ENA is a better biomarker for Pb exposure than MN alone after short-term exposures. The results of the comet assay performed with erythrocytes in vitro exposed to lead confirmed its genotoxic effect and showed that DNA damage increased with increasing exposure time. Moreover, the NRRA clearly indicated that Pb induces a destabilization of the lysosomal membrane. These results demonstrate the potential genotoxicity and cytotoxicity of lead after acute exposures.

  4. Organic extracts of urban air pollution particulate matter (PM2.5)-induced genotoxicity and oxidative stress in human lung bronchial epithelial cells (BEAS-2B cells).

    Science.gov (United States)

    Oh, Seung Min; Kim, Ha Ryong; Park, Yong Joo; Lee, Soo Yeun; Chung, Kyu Hyuck

    2011-08-16

    Traffic is a major source of particulate matter (PM), and ultrafine particulates and traffic intensity probably contribute significantly to PM-related health effects. As a strong relationship between air pollution and motor vehicle-originated pollutants has been shown to exist, air pollution genotoxicity studies of urban cities are steadily increasing. In Korea, the death rate caused by lung cancer is the most rapidly increased cancer death rate in the past 10 years. In this study, genotoxicity of PM2.5 (traffic area in Suwon City, Korea, was studied using cultured human lung bronchial epithelial cells (BEAS-2B) as a model system for the potential inhalation health effects. Organic extract of PM2.5 (CE) generated significant DNA breakage and micronucleus formation in a dose-dependent manner (1μg/cm(3)-50μg/cm(3)). In the acid-base-neutral fractionation of PM2.5, neutral samples including the aliphatic (F3), aromatic (F4) and slightly polar (F5) fractions generated significant DNA breakage and micronucleus formation. These genotoxic effects were significantly blocked by scavenging agents [superoxide dismutase (SOD), sodium selenite (SS), mannitol (M), catalase (CAT)]. In addition, in the modified Comet assay using endonucleases (FPG and ENDOIII), CE and its fractions (F3, F4, and F5) increased DNA breakage compared with control groups, indicating that CE and fractions of PM2.5 induced oxidative DNA damage. These results clearly suggest that PM2.5 collected in the Suwon traffic area has genotoxic effects and that reactive oxygen species may play a distinct role in these effects. In addition, aliphatic/chlorinated hydrocarbons, PAH/alkylderivatives, and nitro-PAH/ketones/quinones may be important causative agents of the genotoxic effects. PMID:21524716

  5. In vivo and in vitro exposures for the evaluation of the genotoxic effects of lead on the Neotropical freshwater fish Prochilodus lineatus

    International Nuclear Information System (INIS)

    In the present study, in vivo and in vitro exposures were used to assess the genotoxicity of lead (Pb) to the freshwater fish Prochilodus lineatus. The comet assay using blood, liver and gill cells, and the occurrence of micronuclei (MN) and other erythrocytic nuclear abnormalities (ENA) were used to assess the genotoxic potential of lead in vivo. Metallothionein content (MT) was measured in fish liver in order to evaluate the protection of fish against Pb toxicity. Fish erythrocytes were exposed to Pb in vitro (1, 3 and 6 h) and the number of viable cells, DNA integrity, using the comet assay, and lysosomal membrane stability, measured by the neutral red retention assay (NRRA) were analyzed. The results of the comet assay after in vivo toxicity tests (6, 24 and 96 h) showed that Pb was genotoxic for all the three tissues analyzed after 96 h exposure. A significant increase in liver MT content was observed after 6 and 24 h of Pb exposure. MN frequency did not increase after Pb exposures, but the frequency of the other ENA, such as kidney-shaped nuclei, segmented nuclei and lobed nuclei, showed a significant increase after 24 and 96 h, indicating that ENA is a better biomarker for Pb exposure than MN alone after short-term exposures. The results of the comet assay performed with erythrocytes in vitro exposed to lead confirmed its genotoxic effect and showed that DNA damage increased with increasing exposure time. Moreover, the NRRA clearly indicated that Pb induces a destabilization of the lysosomal membrane. These results demonstrate the potential genotoxicity and cytotoxicity of lead after acute exposures.

  6. Genotoxicity of Air Borne Particulates Assessed by Comet and the Salmonella Mutagenicity Test in Jeddah, Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Waleed Milaat

    2007-09-01

    Full Text Available Fine airborne respirable particulates less than 10 micrometer (PM10 are considered one of the top environmental public health concerns, since they contain polycyclic aromatic hydrocarbons (PAHs which are among the major carcinogenic compounds found in urban air. The objective of this study is to assess the genotoxicity of the ambient PM10 collected at 11 urban sites in Jeddah, Saudi Arabia. The PM10 extractable organic matter (EOM was examined for its genotoxicity by the single cell gel electrophoresis (SCGE comet assay and the Salmonella mutagenicity (Ames test .Gas chromatography-mass spectrometry was used to quantify 16 PAH compounds in four sites. Samples from oil refinery and heavy diesel vehicles traffic sites showed significant DNA damage causing comet in 20-44% of the cells with tail moments ranging from 0.5-2.0 compared to samples from petrol driven cars and residential area, with comet in less than 2% of the cells and tail moments of < 0.02.In the Ames test, polluted sites showed indirect mutagenic response and caused 20-56 rev/ m3, mean while residential and reference sites caused 2-15 rev /m3. The genotoxicity of the EOM in both tests directly correlated with the amount of organic particulate and the PAHs concentrations in the air samples. The PAHs concentrations ranged between 0.83 ng/m3 in industrial and heavy diesel vehicles traffic sites to 0.18 ng /m3 in the residential area. Benzo(ghipyrene was the major PAH components and at one site it represented 65.4 % of the total PAHs. Samples of the oil refinery site were more genotoxic in the SCGE assay than samples from the heavy diesel vehicles traffic site, despite the fact that both sites contain almost similar amount of PAHs. The opposite was true for the mutagenicity in the Ames test. This could be due to the nature of the EOM in both sites. These findings confirm the genotoxic potency of the PM10 organic extracts to which urban populations are exposed.

  7. Biomonitoring of the genotoxic effects and oxidative potentials of commercial edible dung beetles (Onitis sp.), grasshopper (Caelifera sp.) and mole crickets (Gryllotalpa sp.) in vitro.

    Science.gov (United States)

    Koc, Kubra; Incekara, Umit; Turkez, Hasan

    2014-09-01

    In this investigation, the genotoxic and oxidative effects of water soluble extracts of dung beetles, flying grasshopper and mole crickets have been assessed on cultured human blood cells. The extracts were added to the culture tubes at 12 different concentrations (0-2000 ppm). Micronucleus test was used to monitor the DNA and the chromosomal damage produced by aqueous extracts in vitro. In addition, to assess the oxidative effects, total antioxidant capacity (TAC) and total oxidant status (TOS) levels were also measured. Our results indicated that these extracts did not show genotoxic effects at the tested concentrations. However, the extracts caused dose-dependent alterations in both TAC and TOS levels. Based on the findings, it was concluded that the studied insects can be consumed safely, but it is necessary to consider the cellular damages which are likely to appear depending on oxidative stress at higher concentrations. It has also been suggested that this in vitro approach for oxidative and genotoxicity assessments may be useful to evaluate the potential health risks of edible insects. PMID:24700298

  8. Biomonitoring of the genotoxic effects and oxidative potentials of commercial edible dung beetles (Onitis sp.), grasshopper (Caelifera sp.) and mole crickets (Gryllotalpa sp.) in vitro.

    Science.gov (United States)

    Koc, Kubra; Incekara, Umit; Turkez, Hasan

    2014-09-01

    In this investigation, the genotoxic and oxidative effects of water soluble extracts of dung beetles, flying grasshopper and mole crickets have been assessed on cultured human blood cells. The extracts were added to the culture tubes at 12 different concentrations (0-2000 ppm). Micronucleus test was used to monitor the DNA and the chromosomal damage produced by aqueous extracts in vitro. In addition, to assess the oxidative effects, total antioxidant capacity (TAC) and total oxidant status (TOS) levels were also measured. Our results indicated that these extracts did not show genotoxic effects at the tested concentrations. However, the extracts caused dose-dependent alterations in both TAC and TOS levels. Based on the findings, it was concluded that the studied insects can be consumed safely, but it is necessary to consider the cellular damages which are likely to appear depending on oxidative stress at higher concentrations. It has also been suggested that this in vitro approach for oxidative and genotoxicity assessments may be useful to evaluate the potential health risks of edible insects.

  9. Genotoxicity determinations of coriander drop and extract of Coriander Sativum cultured fibroblast of rat embryo by comet assay

    International Nuclear Information System (INIS)

    The single cell gel electrophoresis (SCGE) or comet assay is a quick, simple and sensitive technique for measuring DNA damage in cell nucleus. It is well known that medicinal herbs play an important role in the life of human beings, thus it is essential to determine their safety as public health is concerned. In this study the genotoxicity of Coriander drop, herbal pharmaceutical product, and the extract of Coriander sativum were examined in cultured fibroblast of rat embryo using comet assay. The thirteen to fifteen days old rat embryos were lysed with tripsin and after certain steps it was centrifuged and then cultured. After three to five passages, different concentrations of each product were applied to the fibroblasts. Lysing, electrophoresis, neutralization and staining were carried out. Finally the slides were analyzed with fluorescence microscope. In the test groups the results indicated that coriander drop at different doses showed some fragmentation of DNA but this damage as a result was deemed to be not significant. However, in the case of Coriander sativum extract the results showed no mutagenic effects in comparison with the positive control group (p<0.05). In conclusion, these herbal products did not show any magnetic effect according to our test, but further genotoxicity assays are recommended. (author)

  10. Studying the genotoxicity of vincristine on human lymphocytes using comet assay, micronucleus assay and TCR gene mutation test in vitro

    International Nuclear Information System (INIS)

    The results of our previous investigation for workers occupationally exposed to vincristine (VCR) indicated that the genetic damage was detectable with comet assay, cytokinesis-block micronucleus (CBMN) assay and housekeeping gene mutation tests. In order to determine the results of above investigation and to inquire further the characteristics of genotoxicity of VCR, the cytogenetic effects of VCR on human lymphocytes were assessed with comet assay, CBMN assay and T-cell receptor (TCR) gene mutation test in vitro. The lymphocytes from two healthy donors were incubated for 24 h at doses of 0.00, 0.01, 0.02, 0.04, and 0.08 μg ml-1 VCR. The results of the present experiment showed that VCR not only could induce DNA damage, increase significantly micronucleus frequencies and the apoptotic cell ratios and decrease the nuclear division index (NDI) with dose-response relationship, but also could produce nucleoplasmic bridges (NPBs), a biomarker of DNA misrepair and/or telomere end-fusions and nuclear buds (NBUDs), a biomarker of elimination of amplified DNA and/or DNA repair complexes. Moreover, VCR could enhance TCR gene mutation frequency (Mf-TCR) of human lymphocytes. There was good correlation between the parameters (mean tail length, mean tail moment, micronucleus frequency, micronucleated frequency and Mf-TCR). The results of present study supported the results of our previous investigation for workers occupationally exposed to VCR, and the genotoxicity of VCR was determined at the different genetic end-points in vitro

  11. The genotoxic effects of benzo[a]pyrene and methamidophos on black porgy evaluated by comet assay

    Science.gov (United States)

    Liu, Rixian; Hong, Huasheng; Wang, Xinhong; Wang, Kejian; Wang, Chunguang

    2005-12-01

    In this study, two common pollutants (benzo[a]pyrene and methamidophos) in marine environment were tested by comet assay for their inducement of in vivo genotoxic effect to the blood cells of black porgy ( Acanthopagrus schlegeli). The fish was exposed to 2 μg/L of benzo[a]pyrene (BaP) and methamidophos, and their mixture. The assay was performed on whole blood at 2 h, 5 h, 24 h and 96 h exposure intervals. A significant increase in DNA damage was observed in each treatment with the pollutants. Additive effect of BaP and methamidophos was also found in the experiment. However, the decrease ratios of DNA damage for 5 h and 96 h exposure interals compared with 2 h and 24 h exposure ones, respectively, were noticed. This phenomenon may be explained by the function of repairing process via enzyme cytochrome P450 in the animal. Evidence of the genotoxicity of organophosphorus pesticides (OPs) and polynuclear aromatic hydrocarbons (PAHs) on marine fish are discussed in this paper.

  12. The genotoxic effects of benzo[a]pyrene and methamidophos on black porgy evaluated by comet assay

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    In this study, two common pollutants (benzo[a]pyrene and methamidophos) in marine environment were tested by comet assay for their inducement of in vivo genotoxic effect to the blood cells of black porgy (Acanthopagrus schlegeli). The fish was exposed to 2 μg/L of benzo[a]pyrene (BaP) and methamidophos, and their mixture. The assay was performed on whole blood at 2 h, 5 h, 24 h and 96 h exposure intervals. A significant increase in DNA damage was observed in each treatment with the pollutants. Additive effect of BaP and methamidophos was also found in the experiment. However, the decrease ratios of DNA damage for 5 h and 96 h exposure interals compared with 2 h and 24 h exposure ones, respectively, were noticed. This phenomenon may be explained by the function of repairing process via enzyme cytochrome P450 in the animal. Evidence of the genotoxicity of organophosphorus pesticides (OPs) and polynuclear aromatic hydrocarbons (PAHs) on marine fish are discussed in this paper.

  13. Lagos lagoon sediment organic extracts and polycyclic aromatic hydrocarbons induce embryotoxic, teratogenic and genotoxic effects in Danio rerio (zebrafish) embryos.

    Science.gov (United States)

    Sogbanmu, Temitope O; Nagy, Eszter; Phillips, David H; Arlt, Volker M; Otitoloju, Adebayo A; Bury, Nic R

    2016-07-01

    An expansion of anthropogenic activity around Lagos lagoon, Nigeria, has raised concerns over increasing contaminants entering the lagoon's ecosystem. The embryotoxicity, teratogenicity and genotoxicity of sediment organic extracts from four sampling zones around Lagos lagoon, Ilaje, Iddo, Atlas Cove and Apapa, as well as the dominant polycyclic aromatic hydrocarbons (PAHs) identified in water measured during the wet season (naphthalene, phenanthrene, pyrene, benzo[a]pyrene and a mixture of these), were assessed with Danio rerio embryos. Embryos were exposed to varying concentrations of toxicants from 0-72 h post-fertilization (hpf). Embryotoxicity at 72 hpf showed a dose-dependent increase in mortality upon exposure to extracts from all zones, except Atlas Cove. Similarly, higher levels of teratogenic effects, such as increased oedema, and haemorrhage and developmental abnormalities resulted from exposure to extracts from Ilaje, Iddo and Apapa zones. Treatment with single PAHs revealed that significant levels of detrimental effects were obtained only for phenanthrene. The modified comet assay revealed that the oxidative damage to DNA was generally low (<12 %) overall for all sediment extracts, but was significantly elevated with Ilaje and Iddo sediment extracts when compared with solvent controls. Oxidative damage was observed with the single PAHs, phenanthrene and benzo[a]pyrene, as well as with the PAH mixture. This study highlights that Lagos lagoon sediment extracts have teratogenic, embryotoxic and genotoxic properties, which are likely due to the high molecular weight PAHs present in the extracts, some of which are known or are suspected human carcinogens. PMID:27068906

  14. In vitro biomonitoring of the genotoxic and oxidative potentials of two commonly eaten insects in southwestern Nigeria.

    Science.gov (United States)

    Memiş, Eray; Türkez, Hasan; Incekara, Ümit; Banjo, Adedoyin Davies; Fasunwon, Bamidele Temitope; Toğar, Başak

    2013-02-01

    In this study, the cytogenetic and oxidative effects of water soluble extracts of two commonly eaten insects, Zonocerus variegatus (Orthoptera: Pyrgomorphidae) and Oryctes boas (Solanales: Solanaceae), in southwestern Nigeria were evaluated on cultured human blood cells. The extracts were added to the cultures at various concentrations (0-2000 ppm). The chromosome aberration and micronucleus tests were used to find out the DNA and chromosomal damage potentials in vitro by aqueous insect extracts. To assess the oxidative effects of these insect extracts, total antioxidant capacity (TAC) and total oxidant status (TOS) levels were also measured. Our results indicated that these extracts did not show genotoxic effects at the tested concentrations. However, the extracts caused dose-dependent alterations in both TAC and TOS levels. Based on the findings, it was concluded that the studied insects can be consumed safely, but it is necessary to consider the cellular damages that are likely to appear depending on the oxidative stress. We also suggest that this in vitro approach for oxidative and genotoxicity assessments may be useful to compare the potential health risks of edible insects.

  15. Identification of early target genes of aflatoxin B1 in human hepatocytes, inter-individual variability and comparison with other genotoxic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Josse, Rozenn; Dumont, Julie; Fautrel, Alain; Robin, Marie-Anne; Guillouzo, André, E-mail: andre.guillouzo@univ-rennes1.fr

    2012-01-15

    Gene expression profiling has recently emerged as a promising approach to identify early target genes and discriminate genotoxic carcinogens from non-genotoxic carcinogens and non-carcinogens. However, early gene changes induced by genotoxic compounds in human liver remain largely unknown. Primary human hepatocytes and differentiated HepaRG cells were exposed to aflatoxin B1 (AFB1) that induces DNA damage following enzyme-mediated bioactivation. Gene expression profile changes induced by a 24 h exposure of these hepatocyte models to 0.05 and 0.25 μM AFB1 were analyzed by using oligonucleotide pangenomic microarrays. The main altered signaling pathway was the p53 pathway and related functions such as cell cycle, apoptosis and DNA repair. Direct involvement of the p53 protein in response to AFB1 was verified by using siRNA directed against p53. Among the 83 well-annotated genes commonly modulated in two pools of three human hepatocyte populations and HepaRG cells, several genes were identified as altered by AFB1 for the first time. In addition, a subset of 10 AFB1-altered genes, selected upon basis of their function or tumor suppressor role, was tested in four human hepatocyte populations and in response to other chemicals. Although they exhibited large variable inter-donor fold-changes, several of these genes, particularly FHIT, BCAS3 and SMYD3, were found to be altered by various direct and other indirect genotoxic compounds and unaffected by non-genotoxic compounds. Overall, this comprehensive analysis of early gene expression changes induced by AFB1 in human hepatocytes identified a gene subset that included several genes representing potential biomarkers of genotoxic compounds. -- Highlights: ► Gene expression profile changes induced by aflatoxin B1 in human hepatocytes. ► AFB1 modulates various genes including tumor suppressor genes and proto-oncogenes. ► Important inter-individual variations in the response to AFB1. ► Some genes also altered by other

  16. Genotoxicity of Pesticide Waste Contaminated Soil and Its Leachate

    Institute of Scientific and Technical Information of China (English)

    S. D. SIVANESAN; K. KRISHNAMURTHI; S. D. WACHASUNDER; T. CHAKRABARTI

    2004-01-01

    Improper land disposal of hazardous waste can result in leaching of hazardous constituents which may contaminate ground and surface water leading to adverse impact on human health and environment consequences. The present study utilized mammalian cell culture for the genotoxicity assessment of waste and its leachate. Methods Genotoxic potential and chemical analysis of pesticide derived tarry waste contaminated soil extract and its leachate was assessed using in vitro human lymphocyte cultures and GC-MS. Results The investigation revealed that the soil extract could cause significant to highly significant genotoxicity in the form of DNA strand break at 25 μL (P<0.01), 50 μL, 100 μL and 200 μL (P<0.001) and chromosomal aberration at 25 μL (P<0.01) and 50 μL and 100 μL (P<0.001). The leachate could cause significant DNA strand break and chromosomal aberration only at 100 μL and 200 μL (P<0.01) dose levels. Conclusion The genotoxicity observed is attributed to carbaril and tetra methyl naphthyl carbamate, the major ingredients of the extracts, as revealed by GC-MS.

  17. Genistein genotoxicity: Critical considerations of in vitro exposure dose

    International Nuclear Information System (INIS)

    The potential health benefits of soy-derived phytoestrogens include their reported utility as anticarcinogens, cardioprotectants and as hormone replacement alternatives in menopause. Although there is increasing popularity of dietary phytoestrogen supplementation and of vegetarian and vegan diets among adolescents and adults, concerns about potential detrimental or other genotoxic effects persist. While a variety of genotoxic effects of phytoestrogens have been reported in vitro, the concentrations at which such effects occurred were often much higher than the physiologically relevant doses achievable by dietary or pharmacologic intake of soy foods or supplements. This review focuses on in vitro studies of the most abundant soy phytoestrogen, genistein, critically examining dose as a crucial determinant of cellular effects. In consideration of levels of dietary genistein uptake and bioavailability we have defined in vitro concentrations of genistein > 5 μM as non-physiological, and thus 'high' doses, in contrast to much of the previous literature. In doing so, many of the often-cited genotoxic effects of genistein, including apoptosis, cell growth inhibition, topoisomerase inhibition and others become less obvious. Recent cellular, epigenetic and microarray studies are beginning to decipher genistein effects that occur at dietarily relevant low concentrations. In toxicology, the well accepted principle of 'the dose defines the poison' applies to many toxicants and can be invoked, as herein, to distinguish genotoxic versus potentially beneficial in vitro effects of natural dietary products such as genistein

  18. Genistein genotoxicity: critical considerations of in vitro exposure dose.

    Science.gov (United States)

    Klein, Catherine B; King, Audrey A

    2007-10-01

    The potential health benefits of soy-derived phytoestrogens include their reported utility as anticarcinogens, cardioprotectants and as hormone replacement alternatives in menopause. Although there is increasing popularity of dietary phytoestrogen supplementation and of vegetarian and vegan diets among adolescents and adults, concerns about potential detrimental or other genotoxic effects persist. While a variety of genotoxic effects of phytoestrogens have been reported in vitro, the concentrations at which such effects occurred were often much higher than the physiologically relevant doses achievable by dietary or pharmacologic intake of soy foods or supplements. This review focuses on in vitro studies of the most abundant soy phytoestrogen, genistein, critically examining dose as a crucial determinant of cellular effects. In consideration of levels of dietary genistein uptake and bioavailability we have defined in vitro concentrations of genistein >5 microM as non-physiological, and thus "high" doses, in contrast to much of the previous literature. In doing so, many of the often-cited genotoxic effects of genistein, including apoptosis, cell growth inhibition, topoisomerase inhibition and others become less obvious. Recent cellular, epigenetic and microarray studies are beginning to decipher genistein effects that occur at dietarily relevant low concentrations. In toxicology, the well accepted principle of "the dose defines the poison" applies to many toxicants and can be invoked, as herein, to distinguish genotoxic versus potentially beneficial in vitro effects of natural dietary products such as genistein. PMID:17688899

  19. Evaluation of the genotoxic activity of dicamba and atrazine herbicides in several Mexican and South American varieties of sweetcorn (Zea mays L.).

    Science.gov (United States)

    Reynoso, M S; Alvarez, C M; De la Cruz, L; Escoto, M D; Sánchez, J J G

    2015-12-11

    Corn is a major crop and various herbicides are used to maximize its production, which include a dicamba-atrazine mixture. This has great advantages, but can also induce DNA damage. Genotoxic activity was assessed by comet assay following application of two concentrations of dicamba-atrazine: 1000-2000 and 2000-4000 ppm. Apical meristem leaf nuclei from 119 varieties of sweetcorn plants from Mexico and South America, and from five commercial sweetcorn hybrids were used. Each accession comprised two individuals per concentration and two controls. Significant genotoxic activity (P 0.05) except (P atrazine mixture caused genetic damage to corn plants, and it suggested that Mexican sweetcorn is more sensitive to dicamba-atrazine than the maize varieties from South America. Neither hybrid status nor the origin avoids DNA damage caused by Marvel. Thus, maize can be useful as a biomonitor of genetic damage induced by chemicals and to identify possible phenotypes based upon the amount of genetic damage induced by herbicides and selection of resistant genotypes.

  20. Photoelectrochemical Sensors for the Rapid Detection of DNA Damage Induced by Some Nanoparticles

    OpenAIRE

    M. Jamaluddin Ahmed; Bin-Tian Zhang; Liang-Hong Guo

    2010-01-01

    Photoelectrochemcal sensors were developed for the rapid detection of oxidative DNA damage induced by titanium dioxide and polystyrene nanoparticles. Each sensor is a multilayer film prepared on a tin oxide nanoparticle electrode using layer- by-layer self assembly and is composed of separate layer of a photoelectrochemical indicator, DNA. The organic compound and heavy metals represent genotoxic chemicals leading two major damaging mechanisms, DNA adduct formation and DNA oxidation. The DN...

  1. DNA damage in male gonad cells of Green mussel (Perna viridis) upon exposure to tobacco products

    Digital Repository Service at National Institute of Oceanography (India)

    Nagarajappa; Ganguly, A.; Goswami, U.

    . Keywords: Genotoxicity, DNA damage, Comet assay, Cigar tobacco extracts, H2O2 Introduction Marine pollution is a global problem and can arise from natural occurrences as well as human activities, resource uses and interventions..., 781, 56-63. Nacci, D.E., Cayula, S., and Eugene, J., (1996). Detection of DNA damage in individual cells from marine organisms using the single gel assay. Aquatic Toxicol., 35,197?219. Ostling, O., and Johanson, K.J., (1984). Microelectrophoretic...

  2. Sun Damage

    Science.gov (United States)

    ... rash and rashes clinical tools newsletter | contact Share | Sun Damage A A A The sun has a profound effect over years of exposure ... changes. Exposure to ultraviolet (UV) light from the sun accounts for most premature skin aging. Many skin ...

  3. AFFINITY OF LIGNIN PREPARATIONS TOWARDS GENOTOXIC COMPOUNDS

    Directory of Open Access Journals (Sweden)

    Božena Košíková

    2009-02-01

    Full Text Available The carcinogenicity and mutagenicity of chemicals may be modulated by other chemicals, including those prepared by organic synthesis. Consid-ering the several drawbacks of synthetic compounds vis-a-vis the human organism, the lignin biomass component was examined for this purpose. The binding affinity of lignin samples prepared by chemical and biological modification of lignin products derived from chemical wood treatment towards for N-nitrosodiethylamine (NDA was examined. The protective role of the lignin samples against carcinogenesis was tested on a well-known model carcinogen, N-methyl-N´-nitro-N-nitrosoguanidine (MNNG. The observed ability of a series of lignin preparations to reduce alkylation damage of deoxyribonucleic acid (DNA on hamster cells in vitro could be explained by their affinity to bind N-nitrosoamines. The results indicate that lignin has potential to protect living organisms against damaging effects of different genotoxicants.

  4. Genotoxic effects of bisphenol A on somatic cells of female mice, alone and in combination with X-rays.

    Science.gov (United States)

    Gajowik, Aneta; Radzikowska, Joanna; Dobrzyńska, Małgorzata M

    2013-10-01

    Bisphenol A (BPA), a monomer used in the manufacture of epoxy, polycarbonate, and polystyrene resins, is a xenoestrogen present in many consumer products. We investigated the effects of 2-week exposure to BPA, either alone or in combination with X-rays, on the induction of DNA damage in somatic cells of female mice in vivo. The micronucleus and alkaline comet assays were used to evaluate genotoxicity. BPA induced DNA strand breaks in lung cells but not in bone marrow lymphocytes, liver, kidney, or spleen cells. Induction of micronuclei was observed only in polychromatic reticulocytes of peripheral blood. Levels of damage following combination exposure to ionizing radiation plus BPA depended on tissue, assay, and time. PMID:23954285

  5. Damage Distributions

    DEFF Research Database (Denmark)

    Lützen, Marie

    2001-01-01

    The purpose of Task 2.2 of the HARDER project is according to the work package description: For various structural configurations of the struck ship and using the results of Task 2.1, the probability distributions for the damage location and size will be derived. The format will be similar to the...... damage statistics and bow height statistics for vessels in the world fleet. The proposals for the p-, r-, and v-factors have been compared to factors from current regulation by examples.......The purpose of Task 2.2 of the HARDER project is according to the work package description: For various structural configurations of the struck ship and using the results of Task 2.1, the probability distributions for the damage location and size will be derived. The format will be similar to the p...... between the damage location, the damage sizes and the main particulars of the struck vessel. From the numerical simulation and the analyse of the damage statistics it is found that the current formulation from the IMO SLF 43/3/2 can be used as basis for determination of the p-, r-, and v...

  6. Replication stress and oxidative damage contribute to aberrant constitutive activation of DNA damage signalling in human gliomas

    DEFF Research Database (Denmark)

    Bartkova, J; Hamerlik, P; Stockhausen, Marie;

    2010-01-01

    brain and grade II astrocytomas, despite the degree of DDR activation was higher in grade II tumors. Markers indicative of ongoing DNA replication stress (Chk1 activation, Rad17 phosphorylation, replication protein A foci and single-stranded DNA) were present in GBM cells under high- or low...... and indicate that replication stress, rather than oxidative stress, fuels the DNA damage signalling in early stages of astrocytoma development.......Malignant gliomas, the deadliest of brain neoplasms, show rampant genetic instability and resistance to genotoxic therapies, implicating potentially aberrant DNA damage response (DDR) in glioma pathogenesis and treatment failure. Here, we report on gross, aberrant constitutive activation of DNA...

  7. Magnetite Nanoparticles Induce Genotoxicity in the Lungs of Mice via Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Yukari Totsuka

    2014-03-01

    Full Text Available Nanomaterials are useful for their characteristic properties and are commonly used in various fields. Nanosized-magnetite (MGT is widely utilized in medicinal and industrial fields, whereas their toxicological properties are not well documented. A safety assessment is thus urgently required for MGT, and genotoxicity is one of the most serious concerns. In the present study, we examined genotoxic effects of MGT using mice and revealed that DNA damage analyzed by a comet assay in the lungs of imprinting control region (ICR mice intratracheally instilled with a single dose of 0.05 or 0.2 mg/animal of MGT was approximately two- to three-fold higher than that of vehicle-control animals. Furthermore, in gpt delta transgenic mice, gpt mutant frequency (MF in the lungs of the group exposed to four consecutive doses of 0.2 mg MGT was significantly higher than in the control group. Mutation spectrum analysis showed that base substitutions were predominantly induced by MGT, among which G:C to A:T transition and G:C to T:A transversion were the most significant. To clarify the mechanism of mutation caused by MGT, we analyzed the formation of DNA adducts in the lungs of mice exposed to MGT. DNA was extracted from lungs of mice 3, 24, 72 and 168 h after intratracheal instillation of 0.2 mg/body of MGT, and digested enzymatically. 8-Oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG and lipid peroxide-related DNA adducts were quantified by stable isotope dilution liquid chromatography-mass spectrometry (LC-MS/MS. Compared with vehicle control, these DNA adduct levels were significantly increased in the MGT-treated mice. In addition to oxidative stress- and inflammation related-DNA adduct formations, inflammatory cell infiltration and focal granulomatous formations were also observed in the lungs of MGT-treated mice. Based on these findings, it is suggested that inflammatory responses are probably involved in the genotoxicity induced by MGT in the lungs of mice.

  8. Correlation between the genotoxicity endpoints measured by two different genotoxicity assays: comet assay and CBMN assay

    Directory of Open Access Journals (Sweden)

    Carina Ladeira

    2015-06-01

    The use of the CBMN assay in in vitro genetic toxicology testing is well established and in fact it has become an accepted standard method to assess the genotoxic hazard of chemicals which led to the development of a special guideline by the Organization for Economic Cooperation and Development (OECD, the OECD 487 guideline (Kirsch-Volders et al., 2014. The CBMN assay is an effective tool for the study of cellular and nuclear dysfunction caused by in vitro or in vivo aging, micronutrient deficiency or excess, genotoxins exposure and genetic defects in genome maintenance. It is also fruitful in the emerging fields of nutrigenomics and toxicogenomics and their combinations, as it becomes increasingly clear that nutrient status also impacts on sensitivity to exogenous genotoxins (Fenech, 2005, 2007. Many results obtained by this assay indicate the potential predictive value of the CBMN assay with respect to cancer risk and validate its use as a test for detecting nutritional, environmental and genetic factors that are potentially carcinogenic. Also it is used by pharmaceutical industry, human biomonitoring of genotoxic exposures and its increasing application in preventive medicine and nutrition and the increased investment in the automation of the CBMN assay are indicative of the increasing importance of this test (Fenech, 2007. The comet assay or single-cell gel electrophoresis (SCGE is a simple, sensitive method for detecting DNA-strand breaks. Cells embedded in agarose on a microscope slide are lysed with detergent and 2.5 M NaCl and fresh Triton X-100 to remove membranes and soluble cell constituents, including most histones, leaving the DNA, still supercoiled and attached to a nuclear matrix, as a nucleoid. A break in one strand of a DNA loop is enough to release the supercoiling, and during electrophoresis the relaxed loops are able to extend towards the anode (Fairbairn et al., 1995; Collins et al., 1997; Moller et al., 2000; Azqueta et al., 2009; Collins

  9. p53 mutant human glioma cells are sensitive to UV-C-induced apoptosis due to impaired cyclobutane pyrimidine dimer removal.

    Science.gov (United States)

    Batista, Luis F Z; Roos, Wynand P; Kaina, Bernd; Menck, Carlos F M

    2009-02-01

    The p53 protein is a key regulator of cell responses to DNA damage, and it has been shown that it sensitizes glioma cells to the alkylating agent temozolomide by up-regulating the extrinsic apoptotic pathway, whereas it increases the resistance to chloroethylating agents, such as ACNU and BCNU, probably by enhancing the efficiency of DNA repair. However, because these agents induce a wide variety of distinct DNA lesions, the direct importance of DNA repair is hard to access. Here, it is shown that the induction of photoproducts by UV light (UV-C) significantly induces apoptosis in a p53-mutated glioma background. This is caused by a reduced level of photoproduct repair, resulting in the persistence of DNA lesions in p53-mutated glioma cells. UV-C-induced apoptosis in p53 mutant glioma cells is preceded by strong transcription and replication inhibition due to blockage by unrepaired photolesions. Moreover, the results indicate that UV-C-induced apoptosis of p53 mutant glioma cells is executed through the intrinsic apoptotic pathway, with Bcl-2 degradation and sustained Bax and Bak up-regulation. Collectively, the data indicate that unrepaired DNA lesions induce apoptosis in p53 mutant gliomas despite the resistance of these gliomas to temozolomide, suggesting that efficiency of treatment of p53 mutant gliomas might be higher with agents that induce the formation of DNA lesions whose global genomic repair is dependent on p53.

  10. Lesion simulating disease 1 and enhanced disease susceptibility 1 differentially regulate UV-C-induced photooxidative stress signalling and programmed cell death in Arabidopsis thaliana.

    Science.gov (United States)

    Wituszyńska, Weronika; Szechyńska-Hebda, Magdalena; Sobczak, Mirosław; Rusaczonek, Anna; Kozłowska-Makulska, Anna; Witoń, Damian; Karpiński, Stanisław

    2015-02-01

    As obligate photoautotrophs, plants are inevitably exposed to ultraviolet (UV) radiation. Because of stratospheric ozone depletion, UV has become more and more dangerous to the biosphere. Therefore, it is important to understand UV perception and signal transduction in plants. In the present study, we show that lesion simulating disease 1 (LSD1) and enhanced disease susceptibility 1 (EDS1) are antagonistic regulators of UV-C-induced programmed cell death (PCD) in Arabidopsis thaliana. This regulatory dependence is manifested by a complex deregulation of photosynthesis, reactive oxygen species homeostasis, antioxidative enzyme activity and UV-responsive genes expression. We also prove that a UV-C radiation episode triggers apoptotic-like morphological changes within the mesophyll cells. Interestingly, chloroplasts are the first organelles that show features of UV-C-induced damage, which may indicate their primary role in PCD development. Moreover, we show that Arabidopsis Bax inhibitor 1 (AtBI1), which has been described as a negative regulator of plant PCD, is involved in LSD1-dependent cell death in response to UV-C. Our results imply that LSD1 and EDS1 regulate processes extinguishing excessive energy, reactive oxygen species formation and subsequent PCD in response to different stresses related to impaired electron transport.

  11. Curcumin nanoparticles loaded hydrogels protects against aflatoxin B1-induced genotoxicity in rat liver.

    Science.gov (United States)

    Abdel-Wahhab, Mosaad A; Salman, Asmaa S; Ibrahim, Mohamed I M; El-Kady, Ahmed A; Abdel-Aziem, Sekena H; Hassan, Nabila S; Waly, Ahmed I

    2016-08-01

    The current study aimed to evaluate the protective role of curcumin nanoparticles loaded hydrogels (Cur-NPs-Hgs) against AFB1-induced genotoxicity in rat liver. Animals were divided into 7 treatment groups and treated orally for 3 weeks as follow: the control group, the group treated with Hgs alone (0.5 ml/rat), the groups treated with low or high dose of Cur-NPs-Hgs (100 or 200 mg/kg b.w), the group treated with AFB1 (0.125 mg/kg b.w) and the groups treated with AFB1 plus the low or high dose of Cur-NPs-Hgs. Blood ant liver samples were collected for different biochemical, genetical, histological and histochemical analysis. The results revealed that the prepared Cur-NPs have nearly spherical shape with average size of 140 ± 20 nm and negative zeta potential value of 30.7 ± 2.57 mV. The in vivo results showed that treatment with AFB1 decreased the body weight accompanied biochemical, genotoxicity and histological disturbances. The combined treatment with AFB1 and Cur-Nps-Hgs at the two tested doses succeeded to induce a significant protection against AFB1. It could be concluded that Cur-NPs-Hgs is a promise candidate to protect against AFB1-induce liver damage in the high incidence area. Moreover, Hgs are excellent candidates as drug delivery system. PMID:27288928

  12. Genotoxicity induced by Roundup® (Glyphosate) in tegu lizard (Salvator merianae) embryos.

    Science.gov (United States)

    Schaumburg, Laura G; Siroski, Pablo A; Poletta, Gisela L; Mudry, Marta D

    2016-06-01

    Environmental contaminants produce multiple adverse consequences at individual, population and ecosystem levels. High volumes of agrochemicals applied to great variety of crops, together with agricultural expansion, generate great concerns due to the impact for the environment and large risk implicated for wildlife. The lack of data on these threats is striking. The tegu lizard (Salvator merianae) is one of the species that live in environments under contaminant effects. Several characteristics allow proposing this species as a potential sentinel organism for the monitoring of pesticides in their habitat. The present study is the first report about genotoxicity in tegu lizard neonates after embryonic exposure to Roundup® (glyphosate 66.2%). The micronucleus test (MN), nuclear abnormalities (NAs) assay and comet assay (CA) were used as biomarkers of genotoxic effects induced in erythrocytes by topical exposure of the eggs to the glyphosate commercial formulation Roundup® (RU), in laboratory controlled conditions. A total of 96 eggs were distributed in six groups exposed to RU (50, 100, 200, 400, 800, 1600μg/egg), one positive control (PC; 200μg cyclophosphamide/egg) and one negative control (NC; distilled water). No teratogenic effects were observed in any of the exposed or control neonates. A significant increase in DNA damage was observed in all concentrations higher than 100μg/egg with respect to NC (p0.05). Our results provide new information about the undesirable effects of the glyphosate-based herbicide formulations RU on this lizard species that inhabits areas permanently exposed to several pesticide formulations. We consider of utmost necessity a strict regulation of the agrochemical application conditions in those environments near to places where wild populations of terrestrial and aquatic species live, in order to minimize the adverse effects on ecosystems. PMID:27155487

  13. Genotoxicity testing of peptides: Folate deprivation as a marker of exaggerated pharmacology

    International Nuclear Information System (INIS)

    The incidence of micronucleated-cells is considered to be a marker of a genotoxic event and can be caused by direct- or indirect-DNA reactive mechanisms. In particular, small increases in the incidence of micronuclei, which are not associated with toxicity in the target tissue or any structurally altering properties of the compound, trigger the suspicion that an indirect mechanism could be at play. In a bone marrow micronucleus test of a synthetic peptide (a dual agonist of the GLP-1 and GIP receptors) that had been integrated into a regulatory 13-week repeat-dose toxicity study in the rat, small increases in the incidence of micronuclei had been observed, together with pronounced reductions in food intake and body weight gain. Because it is well established that folate plays a crucial role in maintaining genomic integrity and pronounced reductions in food intake and body weight gain were observed, folate levels were determined from plasma samples initially collected for toxicokinetic analytics. A dose-dependent decrease in plasma folate levels was evident after 4 weeks of treatment at the mid and high dose levels, persisted until the end of the treatment duration of 13-weeks and returned to baseline levels during the recovery period of 4 weeks. Based on these properties, and the fact that the compound tested (peptide) per se is not expected to reach the nucleus and cause DNA damage, the rationale is supported that the elevated incidence of micronucleated polychromatic erythrocytes is directly linked to the exaggerated pharmacology of the compound resulting in a decreased folate level. - Highlights: • A synthetic peptide has been evaluated for potential genotoxicity • Small increases in an integrated (13-weeks) micronucleus test were observed • Further, animals had a pronounced reductions in food intake and body weight gain • A dose-dependent decrease in plasma folate levels was evident from week 4 onwards • Elevated micronuclei-incidence due to the

  14. Genotoxicity of Chlorpyrifos and the Antimutagenic Role of Lettuce Leaves in Male Mice

    Directory of Open Access Journals (Sweden)

    Kamilia Badrakhan Abdelaziz

    2010-11-01

    Full Text Available Chlorpyrifos [O O-diethyl-O-(3 5 6-trichloro-2-pyridyl-phosphorothioate] is one of the most widelyused organophosphate insecticides. Previous studies proved that chlorpyrifos, at different doses,induced genotoxicity. In Egyptian foods, the residual levels of pesticides are often higher than thosefound in developed country ones. So the aim of this research was to evaluate the genotoxicity of theinsecticide chlorpyrifos at doses equal to its maximum residue limit (MRL in the leafy vegetables, itsdouble and quadruple (0.5, 1 and 2 mg/kg body weight in somatic and germ cells of male mice.In addition to that, evaluating the role of lettuce leaves as antigenotoxic in reducing the genotoxiceffects of chlorpyrifos tested doses when concurrently administrated to these animals. The studywas conducted on adult male laboratory mice at three levels: bone marrow cells as a model formitotic chromosome aberrations, spermatocytes as a model for meiotic chromosomes and spermcount and morphology. The results of the present study indicate that the treatment of male micewith chlorpyrifos by oral gavages for three months induced significant increase in the frequencies oftotal chromosomal aberrations in both somatic and germ cells in relation to control groups. Resultsof the sperm analysis showed that chlorpyrifos induced significant decrease in the sperm countwhen compared to negative control. Furthermore, it induced significant increase in head and tailsperm abnormalities, among which coiled tail was considered the most obvious sperm abnormalityinduced by chlorpyrifos. At the same time, the present study indicated that lettuce leaves feedconcurrently with three doses of chlorpyrifos could not protect cells from damage.

  15. Necdin modulates proliferative cell survival of human cells in response to radiation-induced genotoxic stress

    Directory of Open Access Journals (Sweden)

    Lafontaine Julie

    2012-06-01

    Full Text Available Abstract Background The finite replicative lifespan of cells, termed cellular senescence, has been proposed as a protective mechanism against the proliferation of oncogenically damaged cells, that fuel cancer. This concept is further supported by the induction of premature senescence, a process which is activated when an oncogene is expressed in normal primary cells as well as following intense genotoxic stresses. Thus, deregulation of genes that control this process, like the tumor suppressor p53, may contribute to promoting cancer by allowing cells to bypass senescence. A better understanding of the genes that contribute to the establishment of senescence is therefore warranted. Necdin interacts with p53 and is also a p53 target gene, although the importance of Necdin in the p53 response is not clearly understood. Methods In this study, we first investigated Necdin protein expression during replicative senescence and premature senescence induced by gamma irradiation and by the overexpression of oncogenic RasV12. Gain and loss of function experiments were used to evaluate the contribution of Necdin during the senescence process. Results Necdin expression declined during replicative aging of IMR90 primary human fibroblasts or following induction of premature senescence. Decrease in Necdin expression seemed to be a consequence of the establishment of senescence since the depletion of Necdin in human cells did not induce a senescence-like growth arrest nor a flat morphology or SA-β-galactosidase activity normally associated with senescence. Similarly, overexpression of Necdin did not affect the life span of IMR90 cells. However, we demonstrate that in normal human cells, Necdin expression mimicked the effect of p53 inactivation by increasing radioresistance. Conclusion This result suggests that Necdin potentially attenuate p53 signaling in response to genotoxic stress in human cells and supports similar results describing an inhibitory function

  16. Genotoxicity testing of peptides: Folate deprivation as a marker of exaggerated pharmacology

    Energy Technology Data Exchange (ETDEWEB)

    Guérard, Melanie, E-mail: melanie.guerard@roche.com; Zeller, Andreas; Festag, Matthias; Schubert, Christine; Singer, Thomas; Müller, Lutz

    2014-09-15

    The incidence of micronucleated-cells is considered to be a marker of a genotoxic event and can be caused by direct- or indirect-DNA reactive mechanisms. In particular, small increases in the incidence of micronuclei, which are not associated with toxicity in the target tissue or any structurally altering properties of the compound, trigger the suspicion that an indirect mechanism could be at play. In a bone marrow micronucleus test of a synthetic peptide (a dual agonist of the GLP-1 and GIP receptors) that had been integrated into a regulatory 13-week repeat-dose toxicity study in the rat, small increases in the incidence of micronuclei had been observed, together with pronounced reductions in food intake and body weight gain. Because it is well established that folate plays a crucial role in maintaining genomic integrity and pronounced reductions in food intake and body weight gain were observed, folate levels were determined from plasma samples initially collected for toxicokinetic analytics. A dose-dependent decrease in plasma folate levels was evident after 4 weeks of treatment at the mid and high dose levels, persisted until the end of the treatment duration of 13-weeks and returned to baseline levels during the recovery period of 4 weeks. Based on these properties, and the fact that the compound tested (peptide) per se is not expected to reach the nucleus and cause DNA damage, the rationale is supported that the elevated incidence of micronucleated polychromatic erythrocytes is directly linked to the exaggerated pharmacology of the compound resulting in a decreased folate level. - Highlights: • A synthetic peptide has been evaluated for potential genotoxicity • Small increases in an integrated (13-weeks) micronucleus test were observed • Further, animals had a pronounced reductions in food intake and body weight gain • A dose-dependent decrease in plasma folate levels was evident from week 4 onwards • Elevated micronuclei-incidence due to the

  17. DNA damage checkpoint recovery and cancer development

    International Nuclear Information System (INIS)

    Cell cycle checkpoints were initially presumed to function as a regulator of cell cycle machinery in response to different genotoxic stresses, and later found to play an important role in the process of tumorigenesis by acting as a guard against DNA over-replication. As a counterpart of checkpoint activation, the checkpoint recovery machinery is working in opposition, aiming to reverse the checkpoint activation and resume the normal cell cycle. The DNA damage response (DDR) and oncogene induced senescence (OIS) are frequently found in precancerous lesions, and believed to constitute a barrier to tumorigenesis, however, the DDR and OIS have been observed to be diminished in advanced cancers of most tissue origins. These findings suggest that when progressing from pre-neoplastic lesions to cancer, DNA damage checkpoint barriers are overridden. How the DDR checkpoint is bypassed in this process remains largely unknown. Activated cytokine and growth factor-signaling pathways were very recently shown to suppress the DDR and to promote uncontrolled cell proliferation in the context of oncovirus infection. In recent decades, data from cell line and tumor models showed that a group of checkpoint recovery proteins function in promoting tumor progression; data from patient samples also showed overexpression of checkpoint recovery proteins in human cancer tissues and a correlation with patients' poor prognosis. In this review, the known cell cycle checkpoint recovery proteins and their roles in DNA damage checkpoint recovery are reviewed, as well as their implications in cancer development. This review also provides insight into the mechanism by which the DDR suppresses oncogene-driven tumorigenesis and tumor progression. - Highlights: • DNA damage checkpoint works as a barrier to cancer initiation. • DDR machinary response to genotoxic and oncogenic stress in similar way. • Checkpoint recovery pathways provide active signaling in cell cycle control. • Checkpoint

  18. DNA damage checkpoint recovery and cancer development

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Haiyong [First affiliated hospital, Zhejiang University, School of medicine, Cancer Center, 79 Qingchun Road, Hangzhou 310003 (China); Zhang, Xiaoshan [Department of Genetics, University of Texas M.D. Anderson Cancer Center, Department of Genetics Unit 1010, 1515 Holcombe Blvd. Houston, TX 77030 (United States); Teng, Lisong, E-mail: lsteng@zju.edu.cn [First affiliated hospital, Zhejiang University, School of medicine, Cancer Center, 79 Qingchun Road, Hangzhou 310003 (China); Legerski, Randy J., E-mail: rlegersk@mdanderson.org [Department of Genetics, University of Texas M.D. Anderson Cancer Center, Department of Genetics Unit 1010, 1515 Holcombe Blvd. Houston, TX 77030 (United States)

    2015-06-10

    Cell cycle checkpoints were initially presumed to function as a regulator of cell cycle machinery in response to different genotoxic stresses, and later found to play an important role in the process of tumorigenesis by acting as a guard against DNA over-replication. As a counterpart of checkpoint activation, the checkpoint recovery machinery is working in opposition, aiming to reverse the checkpoint activation and resume the normal cell cycle. The DNA damage response (DDR) and oncogene induced senescence (OIS) are frequently found in precancerous lesions, and believed to constitute a barrier to tumorigenesis, however, the DDR and OIS have been observed to be diminished in advanced cancers of most tissue origins. These findings suggest that when progressing from pre-neoplastic lesions to cancer, DNA damage checkpoint barriers are overridden. How the DDR checkpoint is bypassed in this process remains largely unknown. Activated cytokine and growth factor-signaling pathways were very recently shown to suppress the DDR and to promote uncontrolled cell proliferation in the context of oncovirus infection. In recent decades, data from cell line and tumor models showed that a group of checkpoint recovery proteins function in promoting tumor progression; data from patient samples also showed overexpression of checkpoint recovery proteins in human cancer tissues and a correlation with patients' poor prognosis. In this review, the known cell cycle checkpoint recovery proteins and their roles in DNA damage checkpoint recovery are reviewed, as well as their implications in cancer development. This review also provides insight into the mechanism by which the DDR suppresses oncogene-driven tumorigenesis and tumor progression. - Highlights: • DNA damage checkpoint works as a barrier to cancer initiation. • DDR machinary response to genotoxic and oncogenic stress in similar way. • Checkpoint recovery pathways provide active signaling in cell cycle control. • Checkpoint

  19. Genotoxicity of 2-bromo-3′-chloropropiophenone

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Fanxue; Yan, Jian; Li, Yan [Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079 (United States); Fu, Peter P. [Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079 (United States); Fossom, Linda H.; Sood, Ramesh K.; Mans, Daniel J.; Chu, Pei-I [Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993 (United States); Moore, Martha M. [Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079 (United States); Chen, Tao, E-mail: tao.chen@fda.hhs.gov [Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079 (United States)

    2013-07-15

    Impurities are present in any drug substance or drug product. They can be process-related impurities that are not completely removed during purification or are formed due to the degradation of the drug substance over the product shelf-life. Unlike the drug substance, impurities generally do not have beneficial effects and may present a risk without associated benefit. Therefore, their amount should be minimized. 2-Bromo-3′-chloropropiophenone (BCP) is an impurity of bupropion, a second-generation antidepressant and a smoking cessation aid. The United States Pharmacopeia recommends an acceptable level for BCP that is not more than 0.1% of the bupropion. Because exposure to genotoxic impurities even at low levels is of significant concern, it is important to determine whether or not BCP is genotoxic. Therefore, in this study the Ames test and the in vitro micronucleus assay were conducted to evaluate the genotoxicity of BCP. BCP was mutagenic with S9 metabolic activation, increasing the mutant frequencies in a concentration-dependent manner, up to 22- and 145-fold induction over the controls in Salmonella strains TA100 and TA1535, respectively. BCP was also positive in the in vitro micronucleus assay, resulting in up to 3.3- and 5.1-fold increase of micronucleus frequency for treatments in the absence and presence of S9, respectively; and 9.9- and 7.4-fold increase of aneuploidies without and with S9, respectively. The addition of N-acetyl-L-cysteine, an antioxidant, reduced the genotoxicity of BCP in both assays. Further studies showed that BCP treatment resulted in induction of reactive oxygen species (ROS) in the TK6 cells. The results suggest that BCP is mutagenic, clastogenic, and aneugenic, and that these activities are mediated via generation of reactive metabolites. - Highlights: • 2-Bromo-3′-chloropropiophenone is an impurity of bupropion. • BCP was positive in both the Ames test and the in vitro micronucleus assay. • It induced high frequencies of

  20. Genotoxicity of 2-bromo-3′-chloropropiophenone

    International Nuclear Information System (INIS)

    Impurities are present in any drug substance or drug product. They can be process-related impurities that are not completely removed during purification or are formed due to the degradation of the drug substance over the product shelf-life. Unlike the drug substance, impurities generally do not have beneficial effects and may present a risk without associated benefit. Therefore, their amount should be minimized. 2-Bromo-3′-chloropropiophenone (BCP) is an impurity of bupropion, a second-generation antidepressant and a smoking cessation aid. The United States Pharmacopeia recommends an acceptable level for BCP that is not more than 0.1% of the bupropion. Because exposure to genotoxic impurities even at low levels is of significant concern, it is important to determine whether or not BCP is genotoxic. Therefore, in this study the Ames test and the in vitro micronucleus assay were conducted to evaluate the genotoxicity of BCP. BCP was mutagenic with S9 metabolic activation, increasing the mutant frequencies in a concentration-dependent manner, up to 22- and 145-fold induction over the controls in Salmonella strains TA100 and TA1535, respectively. BCP was also positive in the in vitro micronucleus assay, resulting in up to 3.3- and 5.1-fold increase of micronucleus frequency for treatments in the absence and presence of S9, respectively; and 9.9- and 7.4-fold increase of aneuploidies without and with S9, respectively. The addition of N-acetyl-L-cysteine, an antioxidant, reduced the genotoxicity of BCP in both assays. Further studies showed that BCP treatment resulted in induction of reactive oxygen species (ROS) in the TK6 cells. The results suggest that BCP is mutagenic, clastogenic, and aneugenic, and that these activities are mediated via generation of reactive metabolites. - Highlights: • 2-Bromo-3′-chloropropiophenone is an impurity of bupropion. • BCP was positive in both the Ames test and the in vitro micronucleus assay. • It induced high frequencies of

  1. Sulforaphane inhibits CYP1A1 activity and promotes genotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Fangxing, E-mail: fxyang@zju.edu.cn [MOE Key Laboratory of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058 (China); Zhuang, Shulin [MOE Key Laboratory of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058 (China); Zhang, Chao; Dai, Heping [State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072 (China); Liu, Weiping, E-mail: wliu@zju.edu.cn [MOE Key Laboratory of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058 (China)

    2013-06-15

    Increasing environmental pollution by carcinogens such as some of persistent organic pollutants (POPs) has prompted growing interest in searching for chemopreventive compounds which are readily obtainable. Sulforaphane (SFN) is isolated from cruciferous vegetables and has the potentials to reduce carcinogenesis through various pathways. In this study, we studied the effects of SFN on CYP1A1 activity and genotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The results showed that SFN inhibited TCDD-induced CYP1A1 activity in H4IIE cells by directly inhibiting CYP1A1 activity, probably through binding to aryl hydrocarbon receptor and/or CYP1A1 revealed by molecular docking. However, SFN promoted TCDD-induced DNA damage in yeast cells and reduced the viability of initiated yeast cells. Besides, it is surprising that SFN also failed to reduce genotoxicity induced by other genotoxic reagents which possess different mechanisms to lead to DNA damage. Currently, it is difficult to predict whether SFN has the potentials to reduce the risk of TCDD based on the conflicting observations in the study. Therefore, further studies should be urgent to reveal the function and mechanism of SFN in the stress of such POPs on human health. - Highlights: • Sulforaphane inhibited TCDD-induced CYP1A1 activity in H4IIE cells. • Sulforaphane may bind to aryl hydrocarbon receptor and/or CYP1A1. • Sulforaphane promoted TCDD-induced DNA damage in yeast cells. • Sulforaphane may promote DNA damage by DNA strand breaks or DNA alkylation.

  2. Radiation damage

    CERN Document Server

    Heijne, Erik H M; CERN. Geneva

    1998-01-01

    a) Radiation damage in organic materials. This series of lectures will give an overview of radiation effects on materials and components frequently used in accelerator engineering and experiments. Basic degradation phenomena will be presented for organic materials with comprehensive damage threshold doses for commonly used rubbers, thermoplastics, thermosets and composite materials. Some indications will be given for glass, scintillators and optical fibres. b) Radiation effects in semiconductor materials and devices. The major part of the time will be devoted to treat radiation effects in semiconductor sensors and the associated electronics, in particular displacement damage, interface and single event phenomena. Evaluation methods and practical aspects will be shown. Strategies will be developed for the survival of the materials under the expected environmental conditions of the LHC machine and detectors. I will describe profound revolution in our understanding of black holes and their relation to quantum me...

  3. Genotoxic effects of environmental estrogen-like compounds in CHO-K1 cells.

    Science.gov (United States)

    Tayama, Sumiko; Nakagawa, Yoshio; Tayama, Kuniaki

    2008-01-01

    Some environmental estrogen-like compounds, such as bisphenol A (BPA), 4-nonylphenol (NP), 4-octylphenol (OP), propyl p-hydroxybenzoate (P-PHBA), and butyl p-hydroxybenzoate (B-PHBA), synthetic estrogen, diethylstilbestrol (DES), and natural estrogen, 17beta-estradiol (E2), were studied for their genotoxicity in CHO-K1 cells using sister-chromatid exchange (SCE), chromosome aberration (CA), and DNA strand break (comet) assays. Six of the chemicals, excluding E2, caused DNA migration in the comet assay and induced SCEs at one or more of the highest doses. Among the chemicals, OP produced an especially high incidence of SCEs. Structural CA was induced by five of the chemicals, excluding OP and NP, and BPA, E2, and DES also induced aneuploid cells. E2 and DES particularly increased the rate of polyploidy at high doses. The incidence of colchicine-mitosis-like (c-mitotic) figures suggesting spindle disrupting effects was also detected with five of the chemicals, excluding OP and NP, and six of the chemicals, excluding E2, caused endoreduplication (ERD), a form of nuclear polyploidization induced by block of cell cycle at G2 phase, at one or more high doses. Our present results suggest that OP and NP cause repairable DNA damage, including SCEs, and do not result in CA, while the damage caused by DES, BPA, P-PHBA, and B-PHBA results in the induction of CAs together with SCEs probably because of imperfect repair. We are unable to explain the observation that the DNA damage caused by E2 resulted in CA induction but not DNA migration or SCE induction, except for speculating that the DNA damage is different from that caused by DES and the estrogen-like chemicals. Our findings also suggest that E2, DES and BPA have aneuploidogenic properties, and that the former two of chemicals also are polyploidy-inducing agents. PMID:17913570

  4. Chromium oxide nanoparticle-induced genotoxicity and p53-dependent apoptosis in human lung alveolar cells.

    Science.gov (United States)

    Senapati, Violet Aileen; Jain, Abhishek Kumar; Gupta, Govind Sharan; Pandey, Alok Kumar; Dhawan, Alok

    2015-10-01

    Chromium oxide (Cr2 O3 ) nanoparticles (NPs) are being increasingly used as a catalyst for aromatic compound manufacture, abrading agents and as pigments (e.g., Viridian). Owing to increased applications, it is important to study the biological effects of Cr2 O3 NPs on human health. The lung is one of the main exposure routes to nanomaterials; therefore, the present study was designed to determine the genotoxic and apoptotic effect of Cr2 O3 NPs in human lung epithelial cells (A549). The study also elucidated the molecular mechanism of its toxicity. Cr2 O3 NPs led to DNA damage, which was deduced by comet assay and cytokinesis block micronucleus assay. The damage could be mediated by the increased levels of reactive oxygen species. Further, the oxygen species led to a decrease in mitochondrial membrane potential and an increase in the ratio of BAX/Bcl-2 leading to mitochondria-mediated apoptosis induced by Cr2 O3 NPs, which ultimately leads to cell death. Hence, there is a need of regulations to be imposed in NP usage. The study provided insight into the caspase-dependent mechanistic pathway of apoptosis. PMID:26086747

  5. Evaluation of genotoxic potential throughout the upper and middle stretches of Adige river basin.

    Science.gov (United States)

    Kračun-Kolarević, Margareta; Kolarević, Stoimir; Jovanović, Jovana; Marković, Vanja; Ilić, Marija; Simonović, Predrag; Simić, Vladica; Gačić, Zoran; Diamantini, Elena; Stella, Elisa; Petrović, Mira; Majone, Bruno; Bellin, Alberto; Paunović, Momir; Vuković-Gačić, Branka

    2016-11-15

    In this study a comprehensive genotoxicological survey throughout the upper and middle stretches of Adige river basin is presented. The study was carried out at 7 sites located along the Adige main course and one the most significant tributaries, the Noce creek, both presenting different levels of pollution pressure. To give an insight into the nature of the genotoxic activity we employed the battery of prokaryotic and eukaryotic assays. Mutagenicity in water samples was evaluated by SOS/umuC test in Salmonella typhimurium TA1535/pSK1002. The level of DNA damage as a biomarker of exposure (comet assay) and biomarker of effect (micronucleus assay) and the level of oxidative stress as well (Fpg - modified comet assay) were studied in blood cells of Salmo cenerinus Nardo, 1847 and Salmo marmoratus Cuvier, 1829. Within the applied bioassays, comet assay showed the highest potential for discriminating the sampling sites which are under lesser extent of pressure (sampling sites 1-Barnes at Bresimo and 4-Noce downstream S. Giustina) from the sites under high pressure (sampling sites 5-Noce at Mezzolombardo and 6/7-Adige upstream and downstream municipality of Trento). Significant correlation between the standard and Fpg - modified comet assay indicated that oxidative stress could be a major contributor to observed DNA damage in collected specimens. PMID:27450952

  6. Engineering Deinococcus radiodurans into biosensor to monitor radioactivity and genotoxicity in environment

    Institute of Scientific and Technical Information of China (English)

    GAO GuanJun; FAN Lu; LU HuiMing; HUA YueJin

    2008-01-01

    Based on a genetically modified radioresistant bacteria Deinococcus radiodurans, we constructed a real time whole cell biosensor to monitor radioactivity and genotoxicity in highly radioactive environment. The enhanced green fluorescence protein (eGFP) was fused to the promoter of the crucial DNA damage-inducible recA gone from D. radiodurans, and the consequent DNA fragment (PrecA-egfp) carried by plasmid was introduced into D. radiodurans R1 strain to obtain the biosensor strain DRG300. This engineered strain can express eGFP protein and generate fluorescence in induction of the recA gone promoter. Based on the correlation between fluorescence intensity and protein expression level in live D. radiodurans cells, we discovered that the fluorescence induction of strain DRG300 responds in a remarkable dose-dependent manner when treated with DNA damage sources such as gamma radiation and mitomycin C. It is encouraging to find the widely detective range and high sensitivity of this reconstructed strain comparing with other whole cell biosensors in former reports. These results suggest that the strain DRG300 is a potential whole cell biosensor to construct a detective system to monitor the biological hazards of radioactive and toxic pollutants in environment in real time.

  7. Genotoxic and antigenotoxic activity of acerola (Malpighia glabra L.) extract in relation to the geographic origin.

    Science.gov (United States)

    Nunes, Roberta Da Silva; Kahl, Vivian Francília Silva; Sarmento, Merielen Da Silva; Richter, Marc François; Abin-Carriquiry, Juan Andres; Martinez, Marcela María; Ferraz, Alexandre De Barros Falcão; Da Silva, Juliana

    2013-10-01

    Malpighia glabra L, popularly known as acerola, is considered a functional fruit and therefore is taken to prevent disease or as adjuvant to treatment strategies, since the fruit is an undeniable source of vitamin C, carotenoids, and flavonoids. Acerola is a natural source of vitamin C, flavonoids, and carotenoids. Its chemical composition is affected by genetic uniformity of the orchards and environmental factors. Considering the extensive growth of the culture of acerola in Brazil as well as its widespread use, this study evaluates the genotoxic and antigenotoxic activity of acerola in relation to geographical origin using the comet assay in mice blood cells in vitro. No acerola samples showed potential to induce DNA damage, independently of origin. Also, for antigenotoxicity activity, only the acerola sample from São Paulo reduced DNA damage induced by hydrogen peroxide (by about 56%). The sample from Ceará showed good antioxidant activity by the 2,2-diphenyl-1-picrylhydrazyl assay, in agreement with its higher rutin, quercetin, and vitamin C levels. Additional studies with other treatment regimens are necessary to better understand the impact of the complex mixture of acerola on genomic stability.

  8. Genotoxic properties of representatives of alkylindazoles and aminoalkyl-indoles which are consumed as synthetic cannabinoids.

    Science.gov (United States)

    Koller, Verena J; Ferk, Franziska; Al-Serori, Halh; Mišík, Miroslav; Nersesyan, Armen; Auwärter, Volker; Grummt, Tamara; Knasmüller, Siegfried

    2015-06-01

    Synthetic cannabinoids (SCs) cause similar effects as cannabis and are sold in herbal mixtures. Recent investigations indicate that some of these drugs possess genotoxic properties. Therefore, we tested representatives of two groups, namely, aminoalkylindoles (AM-2201 and UR-144) and 1-alkylindazoles (5F-AKB-48 and AM-2201-IC) in single cell gel electrophoresis and micronucleus (MN) assays with human lymphocytes and in Salmonella/microsome assays. All drugs except AM-2201 caused DNA-migration, the LOELs were between 50 and 75 µM. Furthermore, all SCs caused inhibition of cell division and significant induction of MN which reflect structural and numerical chromosomal aberrations. The LOEL values were 50 µM for UR-144 and 5-AKB-48 and 75 µM for the other drugs. Also the levels of nucleoplasmatic bridges which are formed from dicentric chromosomes were elevated under identical conditions while the frequencies of nuclear buds were not affected. These findings show that representatives of both groups cause chromosomal damage while the negative results in Salmonella assays (in strains TA98, TA100, TA1535, TA1537 and TA102) in absence and presence of metabolic activation indicate that they do not induce gene mutations. Taken together, these findings indicate that SCs may cause adverse health effects in users as a consequence of damage of the genetic material. PMID:25792264

  9. Evaluation of genotoxicity in patients subjected to panoramic radiography by micronucleus assay on epithelial cells of the oral mucosa.

    Directory of Open Access Journals (Sweden)

    Pallak Arora

    2014-02-01

    Full Text Available Radiography is one of the most valuable diagnostic tools used in comprehensive dental care. Although there is no safe level of radiation exposure, the possible risk associated with exposure to radiation, must be elucidated. To date, a variety of assays have been proposed to assess the mutagenic potential of genotoxicants; however, these methods are typically laborious and time consuming. The aim of the present study was to evaluate the possible genotoxic effect of routinely used panoramic radiation exposure in exfoliated epithelial cells as measured by the formation of micronuclei and to compare the genotoxicity of X-rays on keratinized epithelial gingival cells and the nonkeratinized buccal epithelial cells.The study included 53 healthy individuals with a mean age of 25.21 ±12.67 years. Specimens of exfoliated epithelial cells were collected from patients subjected to panoramic radiography before and 10 days after radiation exposure. The cells were stained with Giemsa and evaluated for micronuclei by scoring 1000 cells per slide.In our study, the genotoxic effect of radiation exposure from panoramic radiography showed a statistically significant increase in the MN frequency in buccal epithelial cells. A significant correlation was observed between the age of the subjects and micronuclei, although no such correlation was found between gender and micronuclei count.MN test serves as a simple biomarker indicating the direct exposure to DNA damaging agents such as ionizing radiation, emphasizing great sensitivity even for exposure to low doses during radiation screening. Thus, panoramic dental radiography should be cautiously used only when necessary.

  10. Genotoxicity evaluation and a primary risk assessment of organic pollutants in the drinking water sources of Nanjing, China

    Institute of Scientific and Technical Information of China (English)

    LI Yi-qiang; WU Yu-lin; CHEN Yuan-gao; KONG Zhi-ming

    2006-01-01

    An increasing number of industrial, agricultural, and commercial chemicals in the aquatic environment leads to various deleterious effects on organisms, which is becoming an increasingly serious problem in China. In this study, the comet assay was conducted to investigate the genotoxicity to human body caused by organic concentrates in the drinking water sources of Nanjing City from Yangtze River of China, and health and ecology risk due to expose to these organic pollutants were evaluated with the multimedia environmental assessment system (MEAS). For all the water samples, they were collected from four different locations in the drinking water sourcr samples, es of Nanjing City. The results of the comet assay showed that all the organic concentrates from the water samples could induce different levels DNA damages on human peripheral blood lymphocytes, and a statistically significant difference (p<0.01) was observed compared with the solvent control, which demonstrated the genotoxicity was in existence.According to the ambient severity (AS) of individual compound, we had sorted out the main organic pollutants in the drinking water source of the four waterworks, and the results showed that there was some potential hazard to human body for all the source water,namely the total ambient severity (TAS) of health for each water source was more than 1. However, the TAS of ecology for each water source was less than 1, which indicated that it was safe to ecology. The results of this investigation demonstrate the application of the comet assay and the MEAS in aquatic environmental monitoring studies, and the comet assay found to be fast, sensitive, and suitable for genotoxicity monitoring programs of drinking water source.

  11. Correlation between the genotoxicity endpoints measured by two different genotoxicity assays: comet assay and CBMN assay

    OpenAIRE

    Carina Ladeira; Susana Viegas; Gomes, Manuel C.

    2015-01-01

    The cytokinesis-block micronucleus cytome (CBMN) assay is a comprehensive system for measuring DNA damage; cytostasis and cytotoxicity-DNA damage events are scored specifically in once-divided binucleated cells. The endpoints possible to be measured are micronuclei (MN), a biomarker of chromosome breakage and/or whole chromosome loss, nucleoplasmic bridges (NPB), a biomarker of DNA misrepair and/or telomere end-fusions, and nuclear buds (NBUD), a biomarker of elimination of amplified DNA and/...

  12. Hexavalent chromium is cytotoxic and genotoxic to American alligator cells.

    Science.gov (United States)

    Wise, Sandra S; Wise, Catherine; Xie, Hong; Guillette, Louis J; Zhu, Cairong; Wise, John Pierce; Wise, John Pierce

    2016-02-01

    Metals are a common pollutant in the aquatic ecosystem. With global climate change, these levels are anticipated to rise as lower pH levels allow sediment bound metals to be released. The American alligator (Alligator mississippiensis) is an apex predator in the aquatic ecosystem and is considered a keystone species; as such it serves as a suitable monitor for localized pollution. One metal of increasing concern is hexavalent chromium (Cr(VI)). It is present in the aquatic environment and is a known human carcinogen and reproductive toxicant. We measured the cytotoxicity and genotoxicity of Cr(VI) in American alligator cells derived from scute tissue. We found that particulate and soluble Cr(VI) are both cytotoxic and genotoxic to alligator cells in a concentration-dependent manner. These data suggest that alligators may be used as a model for assessing the effects of environmental Cr(VI) contamination as well as for other metals of concern. PMID:26730726

  13. Assessment of genotoxic potential of Tamra Bhasma (incinerated copper

    Directory of Open Access Journals (Sweden)

    Swapnil Y Chaudhari

    2015-01-01

    Full Text Available Introduction: The presence of metallic content in Ayurvedic drugs became an important burning issue in present days. The usefulness of Bhasmas (incinerated metals/minerals in therapeutics, their safety or toxicity is frequently being raised on different platforms. Considering this, there is a need to develop toxicity profiles of different metals/minerals. Tamra Bhasma (incinerated copper one such metallic formulation is widely used in cardiac and lipid disorders by Ayurvedic Physicians. The present study is aimed to evaluate the genotoxic potential of Tamra Bhasma. Materials and Methods: It was prepared as per classical guidelines and administered to Swiss albino mice for 14 consecutive days. Chromosomal aberration and sperm abnormality assay were studied. Results: All treated groups exhibited significant body weight gain in comparison to cyclophosphamide (CP group. Results revealed no structural deformity in above parameters in comparison to CP group. Conclusion: Reported data showed that both tested samples of Tamra Bhasma were not genotoxic and can be used safely.

  14. Acetaminophen metabolism, cytotoxicity, and genotoxicity in rat primary hepatocyte cultures

    Energy Technology Data Exchange (ETDEWEB)

    Milam, K.M.; Byard, J.L.

    1985-06-30

    Acetaminophen (APAP) metabolism, cytotoxicity, and genotoxicity were measured in primary cultures of rat hepatocytes. Although 3 mM APAP caused a slight increase in cellular release of lactate dehydrogenase into the culture medium, cellular glutathione concentration (an index of APAP metabolism) was reduced by 50%. APAP at 7 mM was significantly more toxic to these hepatocytes and had a similar but more marked effect on glutathione concentrations. In spite of its cytotoxicity, neither dose of APAP stimulated DNA repair synthesis when monitored by the rate of incorporation of (/sup 3/H)thymidine into DNA following exposure to APAP. Thus, although APAP has been shown to be both hepato- and nephrotoxic in several in vivo and in vitro systems, the reactive toxic metabolite of APAP is not genotoxic in rat primary hepatocyte cultures.

  15. Hexavalent chromium is cytotoxic and genotoxic to American alligator cells.

    Science.gov (United States)

    Wise, Sandra S; Wise, Catherine; Xie, Hong; Guillette, Louis J; Zhu, Cairong; Wise, John Pierce; Wise, John Pierce

    2016-02-01

    Metals are a common pollutant in the aquatic ecosystem. With global climate change, these levels are anticipated to rise as lower pH levels allow sediment bound metals to be released. The American alligator (Alligator mississippiensis) is an apex predator in the aquatic ecosystem and is considered a keystone species; as such it serves as a suitable monitor for localized pollution. One metal of increasing concern is hexavalent chromium (Cr(VI)). It is present in the aquatic environment and is a known human carcinogen and reproductive toxicant. We measured the cytotoxicity and genotoxicity of Cr(VI) in American alligator cells derived from scute tissue. We found that particulate and soluble Cr(VI) are both cytotoxic and genotoxic to alligator cells in a concentration-dependent manner. These data suggest that alligators may be used as a model for assessing the effects of environmental Cr(VI) contamination as well as for other metals of concern.

  16. Genotoxic Effects of Chlorpyrifos in Freshwater Fish Cirrhinus mrigala Using Micronucleus Assay

    OpenAIRE

    Anita Bhatnagar; Abhay Singh Yadav; Navneet Cheema

    2016-01-01

    The genotoxicity of pesticides is an issue of worldwide concern and chlorpyrifos is one of the largest selling organophosphate agrochemicals that has been widely detected in surface waters of India. The studies on long term genotoxic biomarkers are limited; therefore, present study was carried out to analyze the incidence of nuclear anomalies in the blood cells of fresh water fish Cirrhinus mrigala using micronucleus (MN) assay as a potential tool for assessment of genotoxicity. Acute toxicit...

  17. Ecotoxicological and Genotoxic Evaluation of Buenos Aires City (Argentina) Hospital Wastewater

    OpenAIRE

    Anahí Magdaleno; Ángela Beatriz Juárez; Valeria Dragani; Magalí Elizabeth Saenz; Marta Paz; Juan Moretton

    2014-01-01

    Hospital wastewater (HWW) constitutes a potential risk to the ecosystems and human health due to the presence of toxic and genotoxic chemical compounds. In the present work we investigated toxicity and genotoxicity of wastewaters from the public hospital of Buenos Aires (Argentina). The effluent from the sewage treatment plant (STP) serving around 10 million inhabitants was also evaluated. The study was carried out between April and September 2012. Toxicity and genotoxicity assessment was per...

  18. Genistein suppresses doxorubicin associated genotoxicity in human lymphocytes

    OpenAIRE

    Beg, Tanveer; Siddique, Yasir H.; Ara, Gulshan; Afzal, Mohammad; Azmi, Asfar S

    2011-01-01

    Doxorubicin is a well-known DNA intercalating chemotherapy drug that is widely used for treatment of different cancers. Its clinical utility is limited due to the observed genotoxic side effects on healthy cells suggesting that newer combination and genoprotective regimens are urgently needed for the management of doxorubicin chemotherapy. Some dietary phytochemicals are well known for their protective mechanism of action and genistein from soy is recognized as an anti-oxidant with similar pr...

  19. Current Studies into the Genotoxic Effects of Nanomaterials

    OpenAIRE

    Cheng-Teng Ng; Li, Jasmine J.; Boon-Huat Bay; Lin-Yue Lanry Yung

    2010-01-01

    Nanotechnology has created opportunities for engineers to manufacture superior and more efficient devices and products. Nanomaterials (NMs) are now widely used in consumer products as well as for research applications. However, while the lists of known toxic effects of nanomaterials and nanoparticles (NPs) continue to grow, there is still a vast gap in our knowledge about the genotoxicity of NMs. In this paper, we highlight some NMs of interest and discuss the current in vivo and in vitro stu...

  20. Antioxidant, genotoxic and antigenotoxic activities of daphne gnidium leaf extracts

    OpenAIRE

    Chaabane Fadwa; Boubaker Jihed; Loussaif Amira; Neffati Aicha; Kilani-Jaziri Somaya; Ghedira Kamel; Chekir-Ghedira Leila

    2012-01-01

    Abstract Background Plants play a significant role in maintaining human health and improving the quality of human life. They serve humans well as valuable components of food, as well as in cosmetics, dyes, and medicines. In fact, many plant extracts prepared from plants have been shown to exert biological activity in vitro and in vivo. The present study explored antioxidant and antigenotoxic effects of Daphne gnidium leaf extracts. Methods The genotoxic potential of petroleum ether, chlorofor...

  1. Cell cycle control, checkpoint mechanisms, and genotoxic stress.

    OpenAIRE

    R.E. Shackelford; Kaufmann, W K; Paules, R S

    1999-01-01

    The ability of cells to maintain genomic integrity is vital for cell survival and proliferation. Lack of fidelity in DNA replication and maintenance can result in deleterious mutations leading to cell death or, in multicellular organisms, cancer. The purpose of this review is to discuss the known signal transduction pathways that regulate cell cycle progression and the mechanisms cells employ to insure DNA stability in the face of genotoxic stress. In particular, we focus on mammalian cell cy...

  2. Evaluation of occupational genotoxic risk in a Brazilian hospital

    OpenAIRE

    2000-01-01

    Many therapeutic, diagnostic and prophylactic procedures used in hospitals are of potential genetic risk. An evaluation was made of genotoxic occupational risk in 42 workers from the Hospital de Clínicas de Porto Alegre, RS, Brazil, who had been occupationally exposed to lead (solder), ethylene oxide (sterilization area), antineoplastic drugs (nurses and pharmacists) or ionizing radiation. They were compared with 42 unexposed individuals. There was an increase in the frequency of binucleated ...

  3. Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells.

    Science.gov (United States)

    Pöttler, Marina; Staicu, Andreas; Zaloga, Jan; Unterweger, Harald; Weigel, Bianca; Schreiber, Eveline; Hofmann, Simone; Wiest, Irmi; Jeschke, Udo; Alexiou, Christoph; Janko, Christina

    2015-01-01

    Nanoparticles that are aimed at targeting cancer cells, but sparing healthy tissue provide an attractive platform of implementation for hyperthermia or as carriers of chemotherapeutics. According to the literature, diverse effects of nanoparticles relating to mammalian reproductive tissue are described. To address the impact of nanoparticles on cyto- and genotoxicity concerning the reproductive system, we examined the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on granulosa cells, which are very important for ovarian function and female fertility. Human granulosa cells (HLG-5) were treated with SPIONs, either coated with lauric acid (SEONLA) only, or additionally with a protein corona of bovine serum albumin (BSA; SEON(LA-BSA)), or with dextran (SEON(DEX)). Both micronuclei testing and the detection of γH2A.X revealed no genotoxic effects of SEON(LA-BSA), SEON(DEX) or SEON(LA). Thus, it was demonstrated that different coatings of SPIONs improve biocompatibility, especially in terms of genotoxicity towards cells of the reproductive system. PMID:26540051

  4. Molecular and cytogenetic assessment of Dipterygium glaucum genotoxicity.

    Science.gov (United States)

    Altwaty, Nada H; El-Sayed, Osama E; Aly, Nariman A H; Baeshen, Mohamed N; Baeshen, Nabih A

    2016-01-01

    The aim of the present study is to assess the genotoxicity of Dipterygium glaucum grows widely in Saudi Arabia desert to produce safety herbal products. This work is considered the first and pioneer report so far due to the lack and poor evaluated reports of the plant species for their mutagensity, genotoxicity and cytogenetics effects. Cytogenetic effects of D. glaucum on mitotic in roots of Vicia faba showed reduction in mitotic activity using three extracts; water, ethanol and ethyl acetate. Chromosomal abnormalities were recorded that included stickiness of chromosomes, chromatin bridge, fragments, lagging chromosome and micronuclei. Protein bands and RAPD analyses of V. faba treated with three D. glaucum extracts revealed some newly induced proteins and DNA fragments and other disappeared. Chemical constitution of the plant species should be identified with their biological activities against human and animal cells like HeLa cancer cell line. We are recommending using additional genotoxicity tests and other toxicity tests on animal culture with different concentrations and also utilizing several drought and heat tolerant genes of the plant species in gene cloning to develop and improve other economical crop plants instead of using the species as oral herbal remedy.

  5. Molecular and cytogenetic assessment of Dipterygium glaucum genotoxicity

    Directory of Open Access Journals (Sweden)

    NADA H. ALTWATY

    2016-01-01

    Full Text Available ABSTRACT The aim of the present study is to assess the genotoxicity of Dipterygium glaucum grows widely in Saudi Arabia desert to produce safety herbal products. This work is considered the first and pioneer report so far due to the lack and poor evaluated reports of the plant species for their mutagensity, genotoxicity and cytogenetics effects. Cytogenetic effects of D. glaucum on mitotic in roots of Vicia faba showed reduction in mitotic activity using three extracts; water, ethanol and ethyl acetate. Chromosomal abnormalities were recorded that included stickiness of chromosomes, chromatin bridge, fragments, lagging chromosome and micronuclei. Protein bands and RAPD analyses of V. faba treated with three D. glaucum extracts revealed some newly induced proteins and DNA fragments and other disappeared. Chemical constitution of the plant species should be identified with their biological activities against human and animal cells like HeLa cancer cell line. We are recommending using additional genotoxicity tests and other toxicity tests on animal culture with different concentrations and also utilizing several drought and heat tolerant genes of the plant species in gene cloning to develop and improve other economical crop plants instead of using the species as oral herbal remedy

  6. Safety pharmacology and genotoxicity evaluation of AVI-4658.

    Science.gov (United States)

    Sazani, Peter; Weller, Doreen L; Shrewsbury, Stephen B

    2010-01-01

    Duchenne muscular dystrophy (DMD) is caused by dystrophin gene mutations. Restoration of dystrophin by exon skipping was demonstrated with the phosphorodiamidate morpholino oligomers (PMO) class of splice-switching oligomers, in both mouse and dog disease models. The authors report the results of Good Laboratory Practice-compliant safety pharmacology and genotoxicity evaluations of AVI-4658, a PMO under clinical evaluation for DMD. In cynomolgus monkeys, no test article-related effects were seen on cardiovascular, respiratory, global neurological, renal, or liver parameters at the maximum feasible dose (320 mg/kg). Genotoxicity battery showed that AVI-4658 has no genotoxic potential at up to 5000 microg/mL in an in vitro mammalian chromosome aberration test and a bacterial reverse mutation assay. In the mouse bone marrow erythrocyte micronucleus test, a single intravenous injection up to 2000 mg/kg was generally well tolerated and resulted in no mutagenic potential. These results allowed initiation of systemic clinical trials in DMD patients in the United Kingdom.

  7. Genotoxicity risk assessment of diversely substituted quinolines using the SOS chromotest.

    Science.gov (United States)

    Duran, Leidy Tatiana Díaz; Rincón, Nathalia Olivar; Galvis, Carlos Eduardo Puerto; Kouznetsov, Vladimir V; Lorenzo, Jorge Luis Fuentes

    2015-03-01

    Quinolines are aromatic nitrogen compounds with wide therapeutic potential to treat parasitic and microbial diseases. In this study, the genotoxicity of quinoline, 4-methylquinoline, 4-nitroquinoline-1-oxide (4-NQO), and diversely functionalized quinoline derivatives and the influence of the substituents (functional groups and/or atoms) on their genotoxicity were tested using the SOS chromotest. Quinoline derivatives that induce genotoxicity by the formation of an enamine epoxide structure did not induce the SOS response in Escherichia coli PQ37 cells, with the exception of 4-methylquinoline that was weakly genotoxic. The chemical nature of the substitution (C-5 to C-8: hydroxyl, nitro, methyl, isopropyl, chlorine, fluorine, and iodine atoms; C-2: phenyl and 3,4-methylenedioxyphenyl rings) of quinoline skeleton did not significantly modify compound genotoxicities; however, C-2 substitution with α-, β-, or γ-pyridinyl groups removed 4-methylquinoline genotoxicity. On the other hand, 4-NQO derivatives whose genotoxic mechanism involves reduction of the C-4 nitro group were strong inducers of the SOS response. Methyl and nitrophenyl substituents at C-2 of 4-NQO core affected the genotoxic potency of this molecule. The relevance of these results is discussed in relation to the potential use of the substituted quinolines. The work showed the sensitivity of SOS chromotest for studying structure-genotoxicity relationships and bioassay-guided quinoline synthesis.

  8. Exposure to runoff from coal-tar-sealed pavement induces genotoxicity and impairment of DNA repair capacity in the RTL-W1 fish liver cell line

    Energy Technology Data Exchange (ETDEWEB)

    Kienzler, Aude, E-mail: aude.kienzler@entpe.fr [Université de Lyon, UMR LEHNA 5023, USC INRA, ENTPE, rue Maurice Audin, Vaulx-en-Velin F-69518 (France); Mahler, Barbara J., E-mail: bjmahler@usgs.gov [U.S. Geological Survey, 1505 Ferguson Lane, Austin, TX 78754 (United States); Van Metre, Peter C., E-mail: pcvanmet@usgs.gov [U.S. Geological Survey, 1505 Ferguson Lane, Austin, TX 78754 (United States); Schweigert, Nathalie [Université de Lyon, UMR LEHNA 5023, USC INRA, ENTPE, rue Maurice Audin, Vaulx-en-Velin F-69518 (France); Devaux, Alain, E-mail: alain.devaux@entpe.fr [Université de Lyon, UMR LEHNA 5023, USC INRA, ENTPE, rue Maurice Audin, Vaulx-en-Velin F-69518 (France); Bony, Sylvie, E-mail: bony@entpe.fr [Université de Lyon, UMR LEHNA 5023, USC INRA, ENTPE, rue Maurice Audin, Vaulx-en-Velin F-69518 (France)

    2015-07-01

    Coal-tar-based (CTB) sealcoat, frequently applied to parking lots and driveways in North America, contains elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) and related compounds. The RTL-W1 fish liver cell line was used to investigate two endpoints (genotoxicity and DNA-repair-capacity impairment) associated with exposure to runoff from asphalt pavement with CTB sealcoat or with an asphalt-based sealcoat hypothesized to contain about 7% CTB sealcoat (AS-blend). Genotoxic potential was assessed by the Formamido pyrimidine glycosylase (Fpg)-modified comet assay for 1:10 and 1:100 dilutions of runoff samples collected from 5 h to 36 d following sealcoat application. DNA-repair capacity was assessed by the base excision repair comet assay for 1:10 dilution of samples collected 26 h and 36 d following application. Both assays were run with and without co-exposure to ultraviolet-A radiation (UVA). With co-exposure to UVA, genotoxic effects were significant for both dilutions of CTB runoff for three of four sample times, and for some samples of AS-blend runoff. Base excision repair was significantly impaired for CTB runoff both with and without UVA exposure, and for AS-blend runoff only in the absence of UVA. This study is the first to investigate the effects of exposure to the complex mixture of chemicals in coal tar on DNA repair capacity. The results indicate that co-exposure to runoff from CT-sealcoated pavement and UVA as much as a month after sealcoat application has the potential to cause genotoxicity and impair DNA repair capacity. - Highlights: • Co-exposure to runoff from coal-tar-sealcoated pavement and UVA caused DNA damage. • Significant genotoxicity occurred with a 1:100 dilution of runoff. • Runoff collected up to 36 d following coal-tar-sealcoat application was genotoxic. • Exposure to runoff from sealed pavement impaired an important DNA repair pathway. • Repair capacity was impaired with a 1:10 dilution of runoff (1:100 not

  9. Exposure to runoff from coal-tar-sealed pavement induces genotoxicity and impairment of DNA repair capacity in the RTL-W1 fish liver cell line

    International Nuclear Information System (INIS)

    Coal-tar-based (CTB) sealcoat, frequently applied to parking lots and driveways in North America, contains elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) and related compounds. The RTL-W1 fish liver cell line was used to investigate two endpoints (genotoxicity and DNA-repair-capacity impairment) associated with exposure to runoff from asphalt pavement with CTB sealcoat or with an asphalt-based sealcoat hypothesized to contain about 7% CTB sealcoat (AS-blend). Genotoxic potential was assessed by the Formamido pyrimidine glycosylase (Fpg)-modified comet assay for 1:10 and 1:100 dilutions of runoff samples collected from 5 h to 36 d following sealcoat application. DNA-repair capacity was assessed by the base excision repair comet assay for 1:10 dilution of samples collected 26 h and 36 d following application. Both assays were run with and without co-exposure to ultraviolet-A radiation (UVA). With co-exposure to UVA, genotoxic effects were significant for both dilutions of CTB runoff for three of four sample times, and for some samples of AS-blend runoff. Base excision repair was significantly impaired for CTB runoff both with and without UVA exposure, and for AS-blend runoff only in the absence of UVA. This study is the first to investigate the effects of exposure to the complex mixture of chemicals in coal tar on DNA repair capacity. The results indicate that co-exposure to runoff from CT-sealcoated pavement and UVA as much as a month after sealcoat application has the potential to cause genotoxicity and impair DNA repair capacity. - Highlights: • Co-exposure to runoff from coal-tar-sealcoated pavement and UVA caused DNA damage. • Significant genotoxicity occurred with a 1:100 dilution of runoff. • Runoff collected up to 36 d following coal-tar-sealcoat application was genotoxic. • Exposure to runoff from sealed pavement impaired an important DNA repair pathway. • Repair capacity was impaired with a 1:10 dilution of runoff (1:100 not

  10. Genotoxicity of irinotecan and its modulation by vitamins A, C and E in human lymphocytes from healthy individuals and cancer patients.

    Science.gov (United States)

    Kontek, R; Drozda, R; Sliwiński, M; Grzegorczyk, K

    2010-03-01

    Many patients being treated for cancer use dietary supplements, particularly antioxidants, in the hope of reducing the toxicity of chemotherapy or radiotherapy. However, clinicians should advise their patients against using antioxidant dietary supplements during chemotherapy. Irinotecan (CPT-11) is a common chemotherapeutic agent, but it causes side effects, including genotoxicity with damages the DNA of blood cells. The aim of this work was to evaluate the modulating effect of A, C and E vitamins on genotoxic activity of irinotecan (CPT-11) and to analyse the efficacy of DNA repair in lymphocytes of both patients with diagnosed colorectal carcinoma and healthy individuals in vitro. In healthy donors' cells CPT-11 did not exert a strong, genotoxic effect, both in the presence of vitamins and without them. In turn, a statistically significant increase of DNA migration in the comet tails was noted in patients' lymphocytes. The presence of vitamins A, C and E in incubation solutions acted synergistically, increasing the level of DNA lesions in cells caused by the exposure of the material on tested irinotecan concentrations. Analysis of the efficacy of DNA repair, performed after 2h of postincubation, showed the decrease of DNA percentage in comet tails in all experimental samples. PMID:19853651

  11. In vivo genotoxicity testing of the amnesic shellfish poison (domoic acid) in piscine erythrocytes using the micronucleus test and the comet assay

    Energy Technology Data Exchange (ETDEWEB)

    Cavas, Tolga [Mersin University, Faculty of Sciences and Letters, Department of Biology, 33343 Mersin (Turkey)], E-mail: tcavas@mersin.edu.tr; Koenen, Serpil [Mersin University, Faculty of Sciences and Letters, Department of Biology, 33343 Mersin (Turkey)

    2008-11-11

    Domoic acid (DA) is a neurotoxic amino acid naturally produced in the marine environment by some diatom species belonging to the genus Pseudo-nitzschia. Although the neurotoxic properties of DA have been demonstrated, very little is known about in vivo genotoxicity of DA on aquatic organisms. In the present paper, an in vivo study on the genotoxic effects of domoic acid was carried out on a fish, Oreochromis niloticus, using the micronucleus test and the comet assay. The fish were exposed to three doses of domoic acid (1, 5 and 10 {mu}g/g body weight) by intracoelomic injections. Ethyl methane sulphonate at a single dose of 5 mg/l was used as positive control. Analysis of micronuclei, nuclear abnormalities and DNA damage were carried out on peripheral erythrocytes sampled 24, 48 and 72 h post-treatment. Our results revealed significant increases in the frequencies of micronuclei, nuclear abnormalities as well as DNA strand breaks and thus demonstrated the genotoxic potential of DA on fish.

  12. Differential effect of manool--a diterpene from Salvia officinalis, on genotoxicity induced by methyl methanesulfonate in V79 and HepG2 cells.

    Science.gov (United States)

    Nicolella, Heloiza Diniz; de Oliveira, Pollyanna Francielli; Munari, Carla Carolina; Costa, Gizela Faleiros Dias; Moreira, Monique Rodrigues; Veneziani, Rodrigo Cassio Sola; Tavares, Denise Crispim

    2014-10-01

    Salvia officinalis (sage) is a perennial woody subshrub native to the Mediterranean region that is commonly used as a condiment and as an anti-inflammatory, antioxidant and antimicrobial agent due to its biological activities. Manool is the most abundant micro-metabolite found in Salvia officinalis essential oils and extracts. We therefore decided to evaluate the cytotoxic, genotoxic and antigenotoxic potential of manool in Chinese hamster lung fibroblasts (V79) and human hepatoma cells (HepG2). Cytotoxicity was assessed by the colony-forming assay in V79 cells and toxic effects were observed at concentrations of up to 8.0 μg/mL. The micronucleus test was used to evaluate the genotoxicity and antigenotoxicity of manool in V79 and HepG2 cells at concentrations of 0.5-6.0 μg/mL and 0.5-8.0 μg/mL, respectively. For evaluation of antigenotoxicity, the concentrations of manool were combined with methyl methanesulfonate (MMS, 44 μg/mL). The results showed a significant increase in the frequency of micronuclei in cultures of both cell lines treated with the highest concentration tested, demonstrating a genotoxic effect. On the other hand, manool exhibited a protective effect against chromosome damage induced by MMS in HepG2 cells, but not in V79 cells. These data suggest that some manool metabolite may be responsible for the antigenotoxic effect observed in HepG2 cells.

  13. Evaluation of the genotoxicity of Euterpe oleraceae Mart. (Arecaceae) fruit oil (açaí), in mammalian cells in vivo.

    Science.gov (United States)

    Marques, E S; Froder, J G; Carvalho, J C T; Rosa, P C P; Perazzo, F F; Maistro, E L

    2016-07-01

    E. oleracea is a tropical plant from the Amazon region, with its fruit used for food, and traditionally, as an antioxidant, anti-inflammatory, hypocholesterolemic, for atherosclerotic disease, and has anticancer properties. The oil of the fruit has antidiarrheic, anti-inflammatory and antinociceptive activities, but without genotoxicity evaluation. Therefore, the aim of this study was to evaluate the genotoxic potential of E. oleracea fruit oil (EOO), in rat cells. Male Wistar rats were treated with EOO by gavage at doses of 30, 100 and 300 mg/kg, for 14 days, within a 24 h interval. The DNA damage in the leukocytes, liver, bone marrow and testicular cells, was assessed by the comet assay, and the clastogenic/aneugenic effects in the bone marrow cells, by the micronucleus test. Our phytochemicals characterization of the EOO showed the presence of vanillic, palmitic, γ-linolenic, linoleic, oleic, cinnamic, caffeic, protocatechuic, ferulic, syringic acids, and flavonoids quercetin and kaempferol rutinoside as the main constituents. Both cytogenetic tests performed showed that EOO presented no significant genotoxic effects in the analyzed cells, at the three tested doses. These results indicate that, under our experimental conditions, E. oleracea fruit oil did not reveal genetic toxicity in rat cells. PMID:27125964

  14. Genotoxic effect of radio marked lymphocytes using Tc-99m complexes; Efecto genotoxico del radiomarcado de linfocitos empleando complejos de Tc-99m

    Energy Technology Data Exchange (ETDEWEB)

    Pedraza L, M.; Ferro F, G.; Mendiola C, M.T.; Morales R, P. [Instituto nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    1997-07-01

    The genotoxic effect of radio marked lymphocytes was evaluated using {sup 99m}-Tc-HMPAO and {sup 99m}-Tc- gentisic acid complexes. With the results of this work it is pretended to contribute to the knowledge of genetic and structural damages that provokes the radiation in the marked lymphocytes. The d, 1-HMPAO was synthesized in laboratory with a yielding of 30 %. The radiochemical purity of the complexes was greater than 85%. Mouse lymphocytes obtained of sanguineous volumes 2 ml were used. The radio marked efficiency of cells was 19.6 {+-} 6.4% and 25.6 {+-} 5.8% for {sup 99m}Tc-HMPAO and {sup 99m} Tc gentisic acid respectively. The genotoxic effect was evaluated using the technique of Unicellular Electrophoresis in Micro gel (Comet assay). The results showed that both {sup 99m} Tc complexes produce genotoxicity due to their capacity to penetrate cells, therefore the Auger and M internal conversion electrons place all their energy obtaining doses of Gray order. (Author)

  15. Lack of genotoxic effect of food dyes amaranth, sunset yellow and tartrazine and their metabolites in the gut micronucleus assay in mice.

    Science.gov (United States)

    Poul, Martine; Jarry, Gérard; Elhkim, Mostafa Ould; Poul, Jean-Michel

    2009-02-01

    The food dyes amaranth, sunset yellow and tartrazine were administered twice, at 24h intervals, by oral gavage to mice and assessed in the in vivo gut micronucleus test for genotoxic effects (frequency of micronucleated cells) and toxicity (apoptotic and mitotic cells). The concentrations of each compound and their main metabolites (sulfanilic acid and naphthionic acid) were measured in faeces during a 24-h period after single oral administrations of the food dyes to mice. Parent dye compounds and their main aromatic amine metabolites were detected in significant amounts in the environment of colonic cells. Acute oral exposure to food dye additives amaranth, sunset yellow and tartrazine did not induce genotoxic effect in the micronucleus gut assay in mice at doses up to 2000 mg/kg b.w. Food dyes administration increased the mitotic cells at all dose levels when compared to controls. These results suggest that the transient DNA damages previously observed in the colon of mice treated by amaranth and tartrazine by the in vivo comet assay [Sasaki, Y.F., Kawaguchi, S., Kamaya, A., Ohshita, M., Kabasawa, K., Iwama, K., Taniguchi, K., Tsuda, S., 2002. The comet assay with 8 mouse organs: results with 39 currently used food additives. Mutat. Res. 519, 103-119] are unable to be fixed in stable genotoxic lesions and might be partly explained by local cytotoxicity of the dyes.

  16. Assessment of genotoxicity and cytotoxicity of standardized aqueous extract from leaves ofErythroxylum cuneatum in human HepG2 and WRL68 cells line

    Institute of Scientific and Technical Information of China (English)

    RK Wesam; AN Ghanya; HH Mizaton; M ILham; A Aishah

    2013-01-01

    Objective:To investigate the cytotoxicity and the genotoxicity of standardized aqueous of dry leaves ofErythroxylum cuneatum(E. cuneatum) in humanHepG2 andWRL68 cells. Methods:The cytotoxicity ofE. cuneatum extract was evaluated by bothMTS andLDH assays. Genotoxicity study onE. cuneatum extract was assessed by the single cell gel electrophoresis (comet assay).The protective effect ofE. cuneatum against menadione-induced cytotoxicity was also investigated.Results:Results from this study showed thatE. cuneatum extract exhibited cytotoxic activities towards the cells withIC50 value of(125±12) and(125±14) μg/mL forHepG2 andWRL68 cells respectively, after72 h incubation period as determined byMTS assay.LDH leakage was detected at(251±19) and(199.5±12.0) μg/mL forHepG2 andWRL68 respectively. Genotoxicity study results showed that treatment withE. cuneatum up to1 mg/mLdid not cause obviousDNA damage inWRL68 andHepG2 cells.Addition ofE. cunaetum did not show significant protection towards menadione inWRL68 andHepG2Cells.Conclusions:E. cuneatum standardized aqueous extract might be developed in order to establish new pharmacological possibilities for its application.

  17. Determination of the main impurities formed after acid hydrolysis of soybean extracts and the in vitro mutagenicity and genotoxicity studies of 5-ethoxymethyl-2-furfural.

    Science.gov (United States)

    Nemitz, Marina C; Picada, Jaqueline N; da Silva, Juliana; Garcia, Ana Letícia H; Papke, Débora K M; Grivicich, Ivana; Steppe, Martin; von Poser, Gilsane L; Teixeira, Helder F

    2016-09-10

    Soybean acid hydrolyzed extracts are raw-materials widely used for manufacturing of pharmaceuticals and cosmetics products due to their high content of isoflavone aglycones. In the present study, the main sugar degradation products 5-hydroxymethyl-2-furfural (HMF) and 5-ethoxymethyl-2-furfural (EMF) were quantitatively determined after acid hydrolysis of extracts from different soybean cultivars by a validated liquid chromatography method. The furanic compounds determined in samples cover the range of 0.16-0.21mg/mL and 0.22-0.33mg/mL for HMF and EMF, respectively. Complementarily, due to the scarce literature regarding the EMF toxicology, this study also assessed the EMF mutagenicity by the Salmonella/microsome test and genotoxicity by the comet assay. The results revealed that EMF did not show mutagenicity at the range of 50-5000μg/plate in S. typhimurium strains TA98, TA97a, TA100, TA102 and TA1535, but induced DNA damage in HepG2 cells at non-cytotoxic doses of 0.1-1.3mg/mL, mainly by oxidative stress mechanisms. Based on literature of HMF genotoxicity, and considering the EMF genotoxicity results herein shown, purification procedures to remove these impurities from extracts are recommended during healthcare products development to ensure the security of the products. PMID:27475406

  18. Effects of cerium dioxide nanoparticles in Oncorhynchus mykiss liver after an acute exposure: assessment of oxidative stress, genotoxicity and histological alterations

    Directory of Open Access Journals (Sweden)

    Ana Cristina Nunes

    2015-12-01

    Full Text Available At present cerium oxide nanoparticles (CeO2 NP have numerous applications ranging from industry to the household, leading to its wide distribution namely in the aquatic environment. The hereby study aimed to assess the toxic effects of CeO2 NPs in Oncorhynchus mykiss liver following an acute exposure (96h to three different concentrations (0.25, 2.5 and 25 mg/L in terms of the genotoxicity (comet assay, oxidative stress response (Catalase CAT; Glutathione S-Transferases GSTs; Thiobarbituric Acid Reactive Substances TBARS and histopathology. CeO2 NP exposure resulted in genotoxic damage in all exposure treatments, inhibition of CAT in the highest concentration and histopathological changes in all exposure concentrations with predominance of progressive and circulatory alterations. However TBARS and GSTs showed no significant differences comparatively to the control (unexposed group. The results suggest that CeO2 NP are able to cause genotoxicity, biochemical impairment and histological alterations in the liver of rainbow trout.

  19. Evaluation of Mango Byproduct Extracts as Antioxidant Against Pb-Acetate-Induced Oxidative Stress and Genotoxicity in Mice

    Directory of Open Access Journals (Sweden)

    Makawy Aida I. El

    2015-03-01

    Full Text Available The antioxidant and antiproliferative properties of mango by-products were investigated. This study was carried out to evaluate the protective role of mango peel or kernel defatted extracts against Pb-acetate adverse effects on oxidant/antioxidant status, liver dysfunction biomarkers, histopathological changes and genotoxicity in male mice. Total phenolic content and antioxidant activity of both extracts were evaluated. Two doses of both extracts (50 and 100 mg/kg were used to evaluate their role against the toxicity of Pb-acetate (500 ppm. Mice given mango extracts with Pb-acetate had significantly lower plasma MDA, AST and ALT and higher glutathione than mice given Pb-acetate alone. Mango extracts prevented the histopathological changes in liver induced by Pb-acetate and decreased the cytotoxicity of lead by increasing the ratio of PCE/NCE. Mango extract treatment reduced the DNA damage induced by Pb-acetate in liver as demonstrated by a reduction in micronuclei and decrease in tail length, tail DNA% and Olive tail moment. It can be concluded that mango by-product extracts have potential to protect from oxidative stress and genotoxicity of lead.

  20. Protective effect of probiotic bacteria against cadmium-induced genotoxicity in rat hepatocytes in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Đurašević Siniša F.

    2012-01-01

    Full Text Available The protective effect of probiotic bacteria against cadmium (Cd-induced genotoxicity was studied in rat hepatocytes in vivo and in vitro. Male Wistar rats, Rattus norvegicus, were treated for five weeks with (i CdCl2 (70 ppm in the drinking water, (ii a mixture of lyophilized probiotic bacteria Lactobacillus rhamnosus, L. acidophilus and Bifido-bacterium longum (5×108 cfu/g of food, or (iii CdCl2 and probiotic bacteria. In addition, single cells obtained from the untreated rat liver were exposed to CdCl2 (70 ppm, probiotic bacteria (1.28 mg/ml, or CdCl2 and probiotic bacteria, for 15 min at 22°C in the dark. The level of Cd-induced DNA damage in hepatocytes was determined by the comet assay. The obtained results show that probiotic bacteria significantly reduced Cd-induced genotoxicity, both in vivo and in vitro (20% and 48%, respectively. Moreover, the toxicity of Cd to lactobacilli in the gastrointestinal tracts of rats was significantly decreased in the probiotic-treated animals. The binding of Cd2+ to probiotic bacteria was proposed as the most probable protection mechanism. [Acknowledgments. This research was financially supported by the Ministry of Education and Science of the Government of Serbia, projects No 172058 and 173023

  1. Genotoxicity of ferric oxide nanoparticles in Raphanus sativus: Deciphering the role of signaling factors, oxidative stress and cell death.

    Science.gov (United States)

    Saquib, Quaiser; Faisal, Mohammad; Alatar, Abdulrahman A; Al-Khedhairy, Abdulaziz A; Ahmed, Mukhtar; Ansari, Sabiha M; Alwathnani, Hend A; Okla, Mohammad K; Dwivedi, Sourabh; Musarrat, Javed; Praveen, Shelly; Khan, Shams T; Wahab, Rizwan; Siddiqui, Maqsood A; Ahmad, Javed

    2016-09-01

    We have studied the genotoxic and apoptotic potential of ferric oxide nanoparticles (Fe2O3-NPs) in Raphanus sativus (radish). Fe2O3-NPs retarded the root length and seed germination in radish. Ultrathin sections of treated roots showed subcellular localization of Fe2O3-NPs, along with the appearance of damaged mitochondria and excessive vacuolization. Flow cytometric analysis of Fe2O3-NPs (1.0mg/mL) treated groups exhibited 219.5%, 161%, 120.4% and 161.4% increase in intracellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), nitric oxide (NO) and Ca(2+) influx in radish protoplasts. A concentration dependent increase in the antioxidative enzymes glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and lipid peroxidation (LPO) has been recorded. Comet assay showed a concentration dependent increase in deoxyribonucleic acid (DNA) strand breaks in Fe2O3-NPs treated groups. Cell cycle analysis revealed 88.4% of cells in sub-G1 apoptotic phase, suggesting cell death in Fe2O3-NPs (2.0mg/mL) treated group. Taking together, the genotoxicity induced by Fe2O3-NPs highlights the importance of environmental risk associated with improper disposal of nanoparticles (NPs) and radish can serve as a good indicator for measuring the phytotoxicity of NPs grown in NP-polluted environment. PMID:27593272

  2. Antifungal activity against Cryptococcus neoformans strains and genotoxicity assessment in human leukocyte cells of Euphorbia tirucalli L.

    Directory of Open Access Journals (Sweden)

    Luís Flávio Souza de Oliveira

    2014-12-01

    Full Text Available In the last times, focus on plant research has increased all over the world. Euphorbia tirucalli L., a plant known popularly as Aveloz, and originally used in Africa, has been drawing attention for its use in the United States and Latin America, both for use as an ornamental plant and as a medicinal plant. E. tirucalli L. is a member of the family Euphorbiaceae and contains many diterpenoids and triterpenoids, in particular phorbol esters, apparently the main constituent of this plant, which are assumed to be responsible for their activities in vivo and in vitro. The in vitro antifungal activities of Euphorbia tirucalli (L. against opportunistic yeasts were studied using microbroth dilution assay. The results showed that aqueous extract and latex preparation were effective against ten clinical strains of Cryptococcus neoformans in vitro (Latex and extract MIC range of 3.2 - > 411 µg/mL. Aiming the safe use in humans, the genotoxic effects of E. tirucalli were evaluated in human leukocytes cells. Our data show that both aqueous extract and latex preparation have no genotoxic effect in human leukocytes cells in vitro. Although the results cannot be extrapolated by itself for use in vivo, they suggest a good perspective for a therapeutic application in future. In conclusion, our results show that the aqueous extract and latex preparation from E. tirucalli L. are antifungal agents effectives against several strains of C. neoformans and do not provoke DNA damage in human leukocyte cells, considering the concentrations tested.

  3. Effects of triclosan and triclocarban on the growth inhibition, cell viability, genotoxicity and multixenobiotic resistance responses of Tetrahymena thermophila.

    Science.gov (United States)

    Gao, Li; Yuan, Tao; Cheng, Peng; Bai, Qifeng; Zhou, Chuanqi; Ao, Junjie; Wang, Wenhua; Zhang, Haimou

    2015-11-01

    The information about adverse effects of emerging contaminants on aquatic protozoa is very scarce. The growth inhibition effect, cell viability, genotoxicity and multixenobiotic resistance (MXR) responses of two commonly used antimicrobial agents, triclosan (TCS) and triclocarban (TCC) to protozoan Tetrahymena thermophila were investigated in this study. The results revealed that TCS and TCC can inhibit the growth of T. thermophila with 24h EC50 values of 1063 and 295μgL(-1), respectively. The impairment of plasma membrane was observed after 2h exposure of TCS or TCC at the level of mg/L. Furthermore, it is noticeable that at environmentally relevant concentration (1.0μgL(-1)), both TCS and TCC can lead to statistically significant DNA damage in T. thermophila, while the inhibition of growth and change of cell viability cannot be observed. Our results firstly provide the evidence for genotoxic effects of TCS and TCC on the freshwater protozoan. Additionally, both TCS and TCC were found to inhibit the efflux transporter activities, with the inhibitory potencies of 39% and 40% (using verapamil as a model inhibitor), respectively. Particularly, TCC could significantly down-regulate the expression of MXR related gene Abcb15, which encodes the membrane efflux protein that acting as P-gp in T. thermophila. The results raise the awareness of potential aquatic ecological and human health risks from the exposure of TCS and TCC, as they might potentiate the toxic effects by chemosensitizing with co-existing toxicants. PMID:26246462

  4. Genotoxic effect of polycyclic aromatic hydrocarbons in the metropolitan area of Porto Alegre, Brazil, evaluated by Helix aspersa (Mueller, 1774)

    Energy Technology Data Exchange (ETDEWEB)

    Ianistcki, M. [Laboratorio de Genetica Toxicologica, Department of Biology, ULBRA, Av. Farroupilha 8001, Pr. 14/Sala 218, Bairro Sao Jose, CEP 92425-900 Canoas, RS (Brazil); Dallarosa, J. [Laboratorio de Ecologia, UFRGS (Brazil); Sauer, C.; Teixeira, C.E. [Fundacao Estadual de Protecao Ambiental Henrique Luis Roessler, FEPAM, RS (Brazil); Silva, J. da, E-mail: juliana.silva@ulbra.b [Laboratorio de Genetica Toxicologica, Department of Biology, ULBRA, Av. Farroupilha 8001, Pr. 14/Sala 218, Bairro Sao Jose, CEP 92425-900 Canoas, RS (Brazil)

    2009-07-15

    The purpose of this study was to biomonitor metropolitan areas of Porto Alegre (Brazil) for PAHs associated with atmospheric particles and check their effects on the DNA of the land mollusk Helix aspersa. The sampling sites are located in an urban area with heavy traffic: (i) Canoas, (ii) Sapucaia do Sul, and (iii) FIERGS/Porto Alegre. The samples were collected during a continuous period of 24 hours during 15 days using Stacked Filter Units (SFU) on polycarbonate filters (two separated size fractions: PM{sub 10-2.5} and PM{sub <2.5}). The concentrations of 16 major PAHs were determined according to EPA. Comet assay on H. aspersa hemolymph cells was chosen for genotoxicity evaluation. This evaluation shows that, in general, the smaller PM-size fractions (PM{sub <2.5}) have the highest genotoxicity and contain higher concentrations of extractable organic matter. In addition, associations between chemical characteristics and PM carcinogenicity tend to be stronger for the smaller PM-size fractions. - DNA damage in H. aspersa exposed to atmospheric particulate in Metropolitan Area of Porto Alegre demonstrated association with PAHs in the fine filter (PM{sub <2.5}).

  5. Response of native flora to inducible genotoxic damage from increased radioactivity around NPP Jaslovske Bohunice, Slovakia

    International Nuclear Information System (INIS)

    It is not generally known that the first serious failure of nuclear power plant (NPP) technology with loss of human lives occurred in NPP Jaslovske Bohunice (Czechoslovakia) in January 1976. A year later the second accident finally broken reactor A1 with large radioactive contamination. This material was later (in 1980) washed into the nearby drainage by the heavy rain. In cleaning procedure, the contaminated soil particles contaminated the slopes of the drainage. These spots have the shape of 'blurs' about 15 cm wide with a scale of contamination from 0,067; 0,15; 2,38; 9,5; 45.5 up to 322 kBq/kg 137Cs. The research was done in cooperation with the Institute of Tumorbiology, University of Vienna, within the grant Action Austria - Slovak Republic. Details of radioactivity at the area were obtained thanks to the Research Institute of the Nuclear Energy in Trnava, Slovakia. In our ten years long-term study of contaminated soil around nuclear power plant (NPP) Jaslovske Bohunice 24 species of local flora were used to show impact of these accidents. The 19 km long banks of the Jaslovske Bohunice NPP waste water recipient has been identified as contaminated by 137Cs. In total, more than 67,000 m2 of river banks have been found as being contaminated at levels exceeding 1 Bq 137Cs/g of soil. Used phytotoxic and cytogenetic -in situ' tests were extended by analyses of pollen grains. Although the dose of some samples of radioactive soil was relatively high (322 kBq kg-1) no any significant impact on the biological level of tested wild plant species was observed. Possible explanation (such as adaptation and resistance) is discussed. (author)

  6. Genotoxic damage in mine workers exposed to diesel exhaust, and the effects of glutathione transferase genotypes

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Gaskell, M; Martin, E A;

    2005-01-01

    This study was performed in an Estonian shale-oil mine with the purpose to develop and apply a number of biomarkers for occupational diesel-exhaust exposure monitoring. Increased breathing-zone exposures to exhaust from operators of diesel-powered trucks in the mine was confirmed in the environme......-DNA-adduct levels and/or that factors other than occupational exposure to diesel exhaust are primary determinants of these DNA-adduct levels....

  7. Genotoxic damage in mine workers exposed to diesel exhaust, and the effects of glutathione transferase genotypes.

    NARCIS (Netherlands)

    Knudsen, L.E.; Gaskell, M.; Martin, E.A.; Poole, J.; Scheepers, P.T.J.; Jensen, A.; Autrup, H.; Farmer, P.

    2005-01-01

    This study was performed in an Estonian shale-oil mine with the purpose to develop and apply a number of biomarkers for occupational diesel-exhaust exposure monitoring. Increased breathing-zone exposures to exhaust from operators of diesel-powered trucks in the mine was confirmed in the environmenta

  8. Genotoxicity, potential cytotoxicity and cell uptake of titanium dioxide nanoparticles in the marine fish Trachinotus carolinus (Linnaeus, 1766)

    Energy Technology Data Exchange (ETDEWEB)

    Vignardi, Caroline P., E-mail: carolpatvig@usp.br [Department of Biological Oceanography, Oceanographic Institute, University of São Paulo, Praça do Oceanogáfico 191, Cidade Universitária, Butantã, São Paulo, SP 05508900 (Brazil); Hasue, Fabio M., E-mail: humbigutis@gmail.com [Department of Biological Oceanography, Oceanographic Institute, University of São Paulo, Praça do Oceanogáfico 191, Cidade Universitária, Butantã, São Paulo, SP 05508900 (Brazil); Sartório, Priscila V., E-mail: pri.sartorio@gmail.com [Department of Biological Oceanography, Oceanographic Institute, University of São Paulo, Praça do Oceanogáfico 191, Cidade Universitária, Butantã, São Paulo, SP 05508900 (Brazil); Cardoso, Caroline M., E-mail: camargonato@gmail.com [Department of Biological Oceanography, Oceanographic Institute, University of São Paulo, Praça do Oceanogáfico 191, Cidade Universitária, Butantã, São Paulo, SP 05508900 (Brazil); Machado, Alex S.D., E-mail: mamiferomarinho@gmail.com [Faculty of Veterinary Medicine, Integrated College North of Minas Osmane Barbosa Avenue, 11111, JK, Montes Claros, MG 39404006 (Brazil); and others

    2015-01-15

    Highlights: • TiO{sub 2}–NP cytogenotoxicity and cell uptake in marine fish was studied. • TiO{sub 2}–NP suspension was in primary particle, agglomerated and aggregated form. • TiO{sub 2}–NP genotoxicity was time/dose dependent and may induce cell uptake. • Methodology proved to be efficient for evaluating the toxic effect of TiO{sub 2}–NP. - Abstract: Nanoparticles have physicochemical characteristics that make them useful in areas such as science, technology, medicine and in products of everyday use. Recently the manufacture and variety of these products has grown rapidly, raising concerns about their impact on human health and the environment. Adverse effects of exposure to nanoparticles have been reported for both terrestrial and aquatic organisms, but the toxic effects of the substances on marine organisms remain poorly understood. The main aim of this study was to evaluate the genotoxicity of TiO{sub 2}–NP in the marine fish Trachinotus carolinus, through cytogenotoxic methods. The fish received two different doses of 1.5 μg and 3.0 μg–TiO{sub 2}–NP g{sup −1} by intraperitoneal injection. Blood samples were collected to analyze erythrocyte viability using the Trypan Blue exclusion test, comet assay (pH > 13), micronucleus (MN) and other erythrocyte nuclear abnormalities (ENA) 24, 48 and 72 h after injection. The possible cell uptake of TiO{sub 2}–NP in fish injected with the higher dose was investigated after 72 h using transmission electron microscopy (TEM). The results showed that TiO{sub 2}–NP is genotoxic and potentially cytotoxic for this species, causing DNA damage, inducing the formation of MN and other ENA, and decreasing erythrocyte viability. TEM examination revealed that cell uptake of TiO{sub 2}–NP was mainly in the kidney, liver, gills and to a lesser degree in muscle. To the extent of the authors’ knowledge, this is the first in vivo study of genotoxicity and other effects of TiO{sub 2}–NP in a marine fish.

  9. Genotoxicity, potential cytotoxicity and cell uptake of titanium dioxide nanoparticles in the marine fish Trachinotus carolinus (Linnaeus, 1766)

    International Nuclear Information System (INIS)

    Highlights: • TiO2–NP cytogenotoxicity and cell uptake in marine fish was studied. • TiO2–NP suspension was in primary particle, agglomerated and aggregated form. • TiO2–NP genotoxicity was time/dose dependent and may induce cell uptake. • Methodology proved to be efficient for evaluating the toxic effect of TiO2–NP. - Abstract: Nanoparticles have physicochemical characteristics that make them useful in areas such as science, technology, medicine and in products of everyday use. Recently the manufacture and variety of these products has grown rapidly, raising concerns about their impact on human health and the environment. Adverse effects of exposure to nanoparticles have been reported for both terrestrial and aquatic organisms, but the toxic effects of the substances on marine organisms remain poorly understood. The main aim of this study was to evaluate the genotoxicity of TiO2–NP in the marine fish Trachinotus carolinus, through cytogenotoxic methods. The fish received two different doses of 1.5 μg and 3.0 μg–TiO2–NP g−1 by intraperitoneal injection. Blood samples were collected to analyze erythrocyte viability using the Trypan Blue exclusion test, comet assay (pH > 13), micronucleus (MN) and other erythrocyte nuclear abnormalities (ENA) 24, 48 and 72 h after injection. The possible cell uptake of TiO2–NP in fish injected with the higher dose was investigated after 72 h using transmission electron microscopy (TEM). The results showed that TiO2–NP is genotoxic and potentially cytotoxic for this species, causing DNA damage, inducing the formation of MN and other ENA, and decreasing erythrocyte viability. TEM examination revealed that cell uptake of TiO2–NP was mainly in the kidney, liver, gills and to a lesser degree in muscle. To the extent of the authors’ knowledge, this is the first in vivo study of genotoxicity and other effects of TiO2–NP in a marine fish

  10. Relation between DNA damage measured by comet assay and OGG1 Ser326Cys polymorphism in antineoplastic drugs biomonitoring

    OpenAIRE

    Carina Ladeira; Susana Viegas; Mário Pádua; Elisabete Carolino; Gomes, Manuel C.; Miguel Brito

    2015-01-01

    Antineoplastic drugs are hazardous chemical agents used mostly in the treatment of patients with cancer, however health professionals that handle and administer these drugs can become exposed and develop DNA damage. Comet assay is a standard method for assessing DNA damage in human biomonitoring and, combined with formamidopyrimidine DNA glycosylase (FPG) enzyme, it specifically detects DNA oxidative damage.The aim of this study was to investigate genotoxic effects in workers occupationally e...

  11. DNA Damage Following Pulmonary Exposure by Instillation to Low Doses of Carbon Black (Printex 90) Nanoparticles in Mice

    DEFF Research Database (Denmark)

    Kyjovska, Zdenka O.; Jacobsen, Nicklas R.; Saber, Anne T.;

    2015-01-01

    of 0.67, 2, 6, and 162 mu g Printex 90 NPCB and vehicle. Cellular composition and protein concentration was evaluated in BAL fluid as markers of inflammatory response and cell damage. DNA strand breaks in BAL cells, lung, and liver tissue were assessed using the alkaline comet assay. The pulmonary......We previously observed genotoxic effects of carbon black nanoparticles at low doses relative to the Danish Occupational Exposure Limit (3.5 mg/m3). Furthermore, DNA damage occurred in broncho-alveolar lavage (BAL) cells in the absence of inflammation, indicating that inflammation is not required...... the comet assay. We interpret the increased DNA strand breaks occurring following these low exposure doses of NPCB as DNA damage caused by primary genotoxicity in the absence of substantial inflammation, cell damage, and acute phase response. Environ. Mol. Mutagen. 56:41-49, 2015. (c) 2014 The Authors...

  12. Recommended lists of genotoxic and non-genotoxic chemicals for assessment of the performance of new or improved genotoxicity tests: a follow-up to an ECVAM workshop.

    Science.gov (United States)

    Kirkland, David; Kasper, Peter; Müller, Lutz; Corvi, Raffaella; Speit, Günter

    2008-05-31

    At a recent ECVAM workshop considering ways to reduce the frequency of irrelevant positive results in mammalian cell genotoxicity tests [D. Kirkland, S. Pfuhler, D. Tweats, M. Aardema, R. Corvi, F. Darroudi, A. Elhajouji, H.-R. Glatt, P. Hastwell, M. Hayashi, P. Kasper, S. Kirchner, A. Lynch, D. Marzin, D. Maurici, J.-R. Meunier, L. Müller, G. Nohynek, J. Parry, E. Parry, V. Thybaud, R. Tice, J. van Benthem, P. Vanparys, P. White, How to reduce false positive results when undertaking in vitro genotoxicity testing and thus avoid unnecessary followup animal tests: Report of an ECVAM Workshop, Mutat. Res. 628 (2007) 31-55], recommendations for improvements/modifications to existing tests, and suggestions for new assays were made. Following on from this, it was important to identify chemicals that could be used in the evaluation of modified or new assays. An expert panel was therefore convened and recommendations made for chemicals to fit three different sets of characteristics, namely: This paper therefore contains these three recommended lists of chemicals and describes how these should be used for any test-evaluation programme. PMID:18539078

  13. Genotoxic effect of substituted phenoxyacetic acids.

    Science.gov (United States)

    Venkov, P; Topashka-Ancheva, M; Georgieva, M; Alexieva, V; Karanov, E

    2000-11-01

    The potential toxic and mutagenic action of 2,4-dichlorophenoxyacetic acid has been studied in different test systems, and the obtained results range from increased chromosomal damage to no effect at all. We reexamined the effect of this herbicide by simultaneous using three tests based on yeast, transformed hematopoietic, and mouse bone marrow cells. The results obtained demonstrated that 2,4-dichlorophenoxyacetic acid has cytotoxic and mutagenic effects. The positive response of yeast and transformed hematopoietic cells was verified in kinetics and dose-response experiments. The analysis of metaphase chromosomes indicated a statistically proved induction of breaks, deletions, and exchanges after the intraperitoneal administration of 2,4-dichlorophenoxyacetic acid in mice. The study of phenoxyacetic acid and its differently chlorinated derivatives showed that cytotoxicity and mutagenicity are induced by chlorine atoms at position 2 and/or 4 in the benzene ring. The mutagenic effect was abolished by introduction of a third chlorine atom at position 5. Thus 2,4,5-trichlorophenoxyacetic acid was found to have very weak, if any mutagenic effect; however, the herbicide preserved its toxic effect.

  14. Application of the SOS/umu test and high-content in vitro micronucleus test to determine genotoxicity and cytotoxicity of nine benzothiazoles.

    Science.gov (United States)

    Ye, Yan; Weiwei, Jiang; Na, Li; Mei, Ma; Kaifeng, Rao; Zijian, Wang

    2014-12-01

    Benzothiazole and benzothiazole derivatives (BTs) have been detected in various environmental matrices as well as in human beings, but little is currently available regarding their toxicities. In our study, genotoxicities of nine BTs (benzothiazole [BT], 2-chlorobenzothiazole [CBT], 2-bromobenzothiazole [BrBT], 2-fluorobenzothiazole [FBT], 2-methylbenzothiazole [MeBT], 2-mercaptobenzothiazole [MBT], 2-aminobenzothiazole [ABT], 2-hydroxy-benzothiazole [OHBT] and 2-methythiobenzothiazole [MTBT]) are comprehensively evaluated by the SOS/umu test using the bacterial Salmonella typhimurium TA1535/pSK1002 for DNA-damaging effect and the high content in vitro micronucleus test using two human carcinoma cells (MGC-803 and A549) for chromosome-damaging effect. The cytotoxicity of BTs on both bacteria and two human cells was also evaluated. Except for the cytotoxic effect of MBT on MGC-803 and A549, the other tested BTs showed more than 50% cytotoxicity at their highest concentrations in a dose-dependent manner, and their LC50s ranged from 19 (MBT in bacteria) to 270 mg l(-1) (CBT in A549). Activation and inactivation were observed for specific BTs after metabolism. On the other hand, no evidence of genotoxicity was obtained for BT, FBT and MBT, and DNA damage was induced by ABT, OHBT, BrBT and MTBT in MGC-803, by MeBT in A549 and by CBT in both cells. Through quantitative structure-activity relationship analysis, two structure alerts for chemical genotoxicity, including heterocyclic amine and hacceptor-path3-hacceptor are present in ABT and OHBT respectively; however, the underlying mechanisms still need further evaluation.

  15. [In vitro study of genotoxic and oxidative effects induced on human pulmonary cells by exposure to PAHs extracted from airborne particulate matter collected in a coke plant].

    Science.gov (United States)

    Cavallo, D; Ursini, C L; Pira, E; Romano, C; Ciervo, A; Maiello, R; Caglieri, A; Iavicoli, S

    2007-01-01

    Genotoxic and oxidative effect of airborne particulate matter collected in a coke plant were evaluated on lung epithelial cells (A549). We aimed to clarify the mechanism of action of complex mixtures of PAHs and to identify biomarkers of effect of lung cancer. Particulate matter was analysed by GC/MS. Genotoxic and oxidative effects induced by the exposure to the extract were evaluated by Fpg comet assay. The cells were exposed for 30 min, 2h and 4h to 0.01%, 0.02% and 0.05% of the extract. We evaluated comet percentage and analysed tail moment values of exposed and unexposed cells treated with Fpg enzyme (TMenz) and untreated (TM) that indicate respectively oxidative and direct DNA damage. We found 0.328 ng/m3 of pyrene, 0.33 ng/m3 of benzo(a)anthracene, 1.073 ng/m3 of benzo(b)fluoranthene, 0.22 ng/m3 of benzo(k)fluoranthene, 0.35 ng/m3 of benzo(a)pyrene, 0.079 ng/m3 of dibenzo(a,h)anthracene and 0.40 ng/m3 of benzo(g,h,i)perylene. A dose-dependent increase, although not significant, of TM and TMenz in the exposed cells in respect to controls was found that indicates a slight increase of both direct and oxidative damage in exposed cells. A slight increase of comet percentage was found at the highest dose. We show the high sensibility of comet assay to measure early DNA damage also at low doses suggesting the use of such test on A549 to evaluate on target organ the effects of complex mixtures of genotoxic substances. PMID:18409689

  16. Titanium dioxide nanoparticles induce genotoxicity but not mutagenicity in golden mussel Limnoperna fortunei.

    Science.gov (United States)

    Girardello, Francine; Custódio Leite, Camila; Vianna Villela, Izabel; da Silva Machado, Miriana; Luiz Mendes Juchem, André; Roesch-Ely, Mariana; Neves Fernandes, Andreia; Salvador, Mirian; Antonio Pêgas Henriques, João

    2016-01-01

    The widespread use of titanium dioxide nanoparticles (TiO2-NP) in consumer products is the cause of its appearance in wastewater and effluents, reaching the aquatic environment. The evaluation of the biological impact of TiO2-NP and the need to understand its ecotoxicological impact to the aquatic ecosystem are of major concern. Bivalve mollusks may represent a target group for nanoparticle toxicity. Limnoperna fortunei (golden mussel), a freshwater bivalve organism that has been employed in biomonitoring environmental conditions. Comet assay, micronucleus test and oxidative damage to lipids and proteins were performed after the golden mussel was exposed to TiO2-NP (1, 5, 10 and 50μgmL(-1)). The results demonstrate that TiO2-NP can damage the DNA of haemocytes after 2h of exposure and the genotoxic activity significantly increased after 4h exposure to TiO2-NP, at all the TiO2-NP concentrations. TiO2-NP was ineffective in causing mutagenicity in the haemolymph cells of golden mussel. The increase in the lipid peroxidation levels and carbonyl proteins after the exposure to TiO2-NP indicates the induction of oxidative stress at 2h exposure with similar results to all TiO2-NP concentrations, but these effects did not occur at 4h exposure. These results demonstrated that, although TiO2-NP is not mutagenic to golden mussel, it does induce DNA damage and oxidative stress in these organisms.

  17. Sesamol attenuates genotoxicity in bone marrow cells of whole-body γ-irradiated mice.

    Science.gov (United States)

    Kumar, Arun; Selvan, Tamizh G; Tripathi, Akanchha M; Choudhary, Sandeep; Khan, Shahanshah; Adhikari, Jawahar S; Chaudhury, Nabo K

    2015-09-01

    Ionising radiation causes free radical-mediated damage in cellular DNA. This damage is manifested as chromosomal aberrations and micronuclei (MN) in proliferating cells. Sesamol, present in sesame seeds, has the potential to scavenge free radicals; therefore, it can reduce radiation-induced cytogenetic damage in cells. The aim of this study was to investigate the radioprotective potential of sesamol in bone marrow cells of mice and related haematopoietic system against radiation-induced genotoxicity. A comparative study with melatonin was designed for assessing the radioprotective potential of sesamol. C57BL/6 mice were administered intraperitoneally with either sesamol or melatonin (10 and 20mg/kg body weight) 30 min prior to 2-Gy whole-body irradiation (WBI) and sacrificed after 24h. Total chromosomal aberrations (TCA), MN and cell cycle analyses were performed using bone marrow cells. The comet assay was performed on bone marrow cells, splenocytes and lymphocytes. Blood was drawn to study haematological parameters. Prophylactic doses of sesamol (10 and 20mg/kg) in irradiated mice reduced TCA and micronucleated polychromatic erythrocyte frequency in bone marrow cells by 57% and 50%, respectively, in comparison with radiation-only groups. Sesamol-reduced radiation-induced apoptosis and facilitated cell proliferation. In the comet assay, sesamol (20mg/kg) treatment reduced radiation-induced comets (% DNA in tail) compared with radiation only (P < 0.05). Sesamol also increased granulocyte populations in peripheral blood similar to melatonin. Overall, the radioprotective efficacy of sesamol was found to be similar to that of melatonin. Sesamol treatment also showed recovery of relative spleen weight at 24h of WBI. The results strongly suggest the radioprotective efficacy of sesamol in the haematopoietic system of mice. PMID:25863274

  18. The evaluation Genotoxic Risks in Medical Personnel Occupationally Exposed to Ultrasound: the Alkaline Comet Assay Study

    International Nuclear Information System (INIS)

    The use of ultrasound devices in medical diagnosis has experienced a phenomenal growth in recent years. Therefore it has become important to check its genetic harmlessness, especially in occupationally exposed medical personnel. In the present study, the alkaline comet assay was selected as a sensitive bio marker of exposure to evaluate the levels of primary DNA damage in peripheral blood leukocytes of ultrasound-exposed and corresponding control subjects. Exposed and control groups comprised of 30 subjects of similar age and smoking habits. The venous blood samples were processed by standard come assay procedure; they were embedded into agarose microgel, subjected to lysis, denaturation and electrophoresis in alkaline conditions. The extent of DNA migration in leukocytes was assessed by measuring of comet tail length and tail moment. A total of 100 randomly captured comets from each slide were examined using an epifluorescent microscope connected through a black and white camera to an computerising image system. The results obtained indicate potentially geonotixic effects of daily occupational exposure to ultrasound with significant increased values of comet tail length and tail moment measured in leukocytes of the exposed subjects compared to control. Within exposed group significant inter-individual differences in DNA damage were assessed, indicating different genome sensitivity. It was also observed that smoking habits influenced the levels of primary DNA damage in some control and exposed subjects. In spite of their limitations, results of present comet assay study indicate that individuals occupationally exposed to ultrasound may experience an increased genotoxic risk and strongly emphasize the need for more research into the nature and extent of the biological consequences to medical personnel working with ultrasound. (Author) 43 refs

  19. Testing the genotoxicity of some perfumes with high diethylphthalate (DEP levels using comet assay

    Directory of Open Access Journals (Sweden)

    Iman Al-Saleh

    2015-05-01

    Full Text Available The presence of phthalates in perfumes has gained recently some attention since these chemicals are added sometimes intentionally as a fixative. Our previous study tested 47 branded perfumes sold in Saudi market and found 68% of tested samples had diethylphthalate (DEP, above reported threshold limit of 1 ppm. Of these phthalates, DEP was found to have the highest mean value (1621.63 ppm. These results enticed us to test the potential genotoxicity of 7 brands in which their DEP contents were in the range of 1.06 ppm to 23649.3 ppm in human TK-6 cells using single cell gel electrophoresis assay (comet assay. Cells were exposed to 400 µl perfume for 2 hrs, at room temperature. Tail moment was (TM used as a metric measure for DNA damage and 25 cells per sample were determined by image analysis software. Four perfumes with DEP above 40 ppm produced significant DNA damage in TK-6 cells with TM of 54.27 ± 1.04, n=500 compare to the other 3 perfumes with DEP < 2 ppm (21.94 ± 1.09, n=300, untreated cells (2.99 ± 0.17, n=250 and cells induced with ethanol (33.76 ± 1.4, n=75 or methanol (23.82 ± 1.84, n=100 which are the vehicles used in perfume's preparations. The results suggest that DEP in perfumes might be one of the ingredients that provoked DNA damage; however, further investigation is required confirming our observation.

  20. Study on the Cytotoxic, Genotoxic and Clastogenic Potential of Attalea phalerata Mart. ex Spreng. Oil Pulp In Vitro and In Vivo Experimental Models

    Science.gov (United States)

    Lima Tolouei Menegati, Sara Emilia; Karenina Traesel, Giseli; Souza de Araújo, Flávio Henrique; Honaiser Lescano, Caroline; Moraes Peixoto, Sara; Mao Silva, Felipe Ariel; Heredia Vieira, Silvia Cristina; do Carmo Vieira, Maria; Oesterreich, Silvia Aparecida

    2016-01-01

    Attalea phalerata Mart. ex Spreng. (Arecaceae), popularly known as “bacuri”, is used in Brazilian folk medicine. Its oil is used orally to relieve pulmonary congestion and joint pain. In topical applications, it is applied as an effective hair tonic and anti-dandruff. The in natura pulp and its nuts are used as food because of its nutritional value. Despite its use in folk medicine, there is a lack of data regarding its in vivo/in vitro cytotoxic/genotoxic and clastogenic effects. Therefore, in this study, we evaluated the cytotoxic, genotoxic and clastogenic effects of Attalea phalerata Mart. ex Spreng. oil (APMO) in vitro and in vivo. For the analysis of cytotoxic potential, the Artemia salina and MTT (3-(4,5-dimethizzol-zyl)-2,5-diphenyltetrazolium bromide) assays were performed. Possible cytotoxic, genotoxic and clastogenic effects of APMO intake were determined by performing the comet and micronucleus assays. Male and female Wistar rats were orally treated with doses of 125, 250, 500 or 1000 mg.kg-1 of the APMO daily for 28 consecutive days (four weeks). The results showed that the APMO did not induce cell death in the experiments of Artemia salina and MTT, indicating that it has no cytotoxicity. The APMO did not cause significant damage to the DNA of the rats in the four doses used when compared to the negative control group (saline + Tween® 80). The APMO did not present any significant increase in micronucleated polychromatic erythrocytes (MNPCEs) for the four tested doses. When compared to the positive control group, all groups (comet and micronucleus tests) were statistically different. These data suggest that the administration of Attalea phalerata Mart oil. ex Spreng does not cause cytotoxicity, genotoxicity and clastogenicity in experimental models in vitro and in vivo following oral administration in this study. PMID:27764219

  1. In vitro evaluation of the cyto-genotoxic potential of Ruthenium(II) SCAR complexes: a promising class of antituberculosis agents.

    Science.gov (United States)

    De Grandis, Rone Aparecido; Resende, Flávia Aparecida; da Silva, Monize Martins; Pavan, Fernando Rogério; Batista, Alzir Azevedo; Varanda, Eliana Aparecida

    2016-03-01

    Tuberculosis is a top infectious disease killer worldwide, caused by the bacteria Mycobacterium tuberculosis. Increasing incidences of multiple drug-resistance (MDR) strains are emerging as one of the major public health threats. However, the drugs in use are still incapable of controlling the appalling upsurge of MDR. In recent years a marked number of research groups have devoted their attention toward the development of specific and cost-effective antimicrobial agents against targeted MDR-Tuberculosis. In previous studies, ruthenium(II) complexes (SCAR) have shown a promising activity against MDR-Tuberculosis although few studies have indeed considered ruthenium toxicity. Therefore, within the preclinical requirements, we have sought to determine the cyto-genotoxicity of three SCAR complexes in this present study. The treatment with the SCARs induced a concentration-dependent decrease in cell viability in CHO-K1 and HepG2 cells. Based on the clonogenic survival, SCAR 5 was found to be more cytotoxic while SCAR 6 exhibited selectivity action on tumor cells. Although SCAR 4 and 5 did not indicate any mutagenic activity as evidenced by the Ames and Cytokinesis block micronucleus cytome assays, the complex SCAR 6 was found to engender a frameshift mutation detected by Salmonella typhimurium in the presence of S9. Similarly, we observed a chromosomal damage in HepG2 cells with significant increases of micronuclei and nucleoplasmic bridges. These data indicate that SCAR 4 and 5 complexes did not show genotoxicity in our models while SCAR 6 was considered mutagenic. This study presented a comprehensive genotoxic evaluation of SCAR complexes were shown to be genotoxic in vitro. All in all, further studies are required to fully elucidate how the properties can affect human health.

  2. Recent Advances in In Vivo Genotoxicity Testing: Prediction of Carcinogenic Potential Using Comet and Micronucleus Assay in Animal Models

    OpenAIRE

    Kang, Seung Hun; Kwon, Jee Young; Lee, Jong Kwon; Seo, Young Rok

    2013-01-01

    Genotoxic events have been known as crucial step in the initiation of cancer. To assess the risk of cancer, genotoxicity assays, including comet, micronucleus (MN), chromosomal aberration, bacterial reverse, and sister chromatid exchange assay, can be performed. Compared with in vitro genotoxicity assay, in vivo genotoxicity assay has been used to verify in vitro assay result and definitely provide biological significance for certain organs or cell types. The comet assay can detect DNA strand...

  3. Polyomavirus interaction with the DNA damage response

    Institute of Scientific and Technical Information of China (English)

    Joshua; L.Justice; Brandy; Verhalen; Mengxi; Jiang

    2015-01-01

    Viruses are obligate intracellular parasites that subvert cellular metabolism and pathways to mediate their own replication—normally at the expense of the host cell. Polyomaviruses are a group of small DNA viruses, which have long been studied as a model for eukaryotic DNA replication. Polyomaviruses manipulate host replication proteins, as well as proteins involved in DNA maintenance and repair, to serve as essential cofactors for productive infection. Moreover, evidence suggests that polyomavirus infection poses a unique genotoxic threat to the host cell. In response to any source of DNA damage, cells must initiate an effective DNA damage response(DDR) to maintain genomic integrity, wherein two protein kinases, ataxia telangiectasia mutated(ATM) and ATM- and Rad3-related(ATR), are major regulators of DNA damage recognition and repair. Recent investigation suggests that these essential DDR proteins are required for productive polyomavirus infection. This review will focus on polyomaviruses and their interaction with ATMand ATR-mediated DNA damage responses and the effect of this interaction on host genomic stability.

  4. Acetylation dynamics of human nuclear proteins during the ionizing radiation-induced DNA damage response

    DEFF Research Database (Denmark)

    Bennetzen, Martin; Andersen, J.S.; Lasen, D.H.;

    2013-01-01

    Genotoxic insults, such as ionizing radiation (IR), cause DNA damage that evokes a multifaceted cellular DNA damage response (DDR). DNA damage signaling events that control protein activity, subcellular localization, DNA binding, protein-protein interactions, etc. rely heavily on time...... to assess lysine acetylation status and thereby validate the mass spectrometry data. We thus present evidence that nuclear proteins, including those known to regulate cellular functions via epigenetic modifications of histones, are regulated by (de)acetylation in a timely manner upon cell's exposure...

  5. Histone H3 lysine 56 acetylation and the response to DNA replication fork damage

    DEFF Research Database (Denmark)

    Wurtele, Hugo; Kaiser, Gitte Schalck; Bacal, Julien;

    2012-01-01

    In Saccharomyces cerevisiae, histone H3 lysine 56 acetylation (H3K56ac) occurs in newly synthesized histones that are deposited throughout the genome during DNA replication. Defects in H3K56ac sensitize cells to genotoxic agents, suggesting that this modification plays an important role in the DNA...... damage response. However, the links between histone acetylation, the nascent chromatin structure, and the DNA damage response are poorly understood. Here we report that cells devoid of H3K56ac are sensitive to DNA damage sustained during transient exposure to methyl methanesulfonate (MMS) or camptothecin...

  6. Bioactivation and genotoxicity of the herbal constituents safrole, estragole and methyleugenol

    NARCIS (Netherlands)

    Jeurissen, S.M.F.

    2007-01-01

    The herbal constituents safrole, estragole, and methyleugenol, belonging to the chemical class of the alkenylbenzenes, are genotoxic and carcinogenic compounds. The genotoxicity of these alkenylbenzenes proceeds via electrophilic metabolites generated bycytochromeP450 enzym

  7. GENOTOXICITY OF TEN CIGARETTE SMOKE CONDENSATES IN FOUR TEST SYSTEMS: COMPARISONS AMONG ASSAYS AND CONDENSATES

    Science.gov (United States)

    The particulate fraction of cigarette smoke, cigarette smoke condensate (CSC), is genotoxic in many short-term in vitro tests and carcinogenic in rodents. However, no study has evaluatedd a set of CSCs prepared from a diverse set of cigarettes in a variety of short-term genotoxic...

  8. DNA damage profiles induced by sunlight at different latitudes.

    Science.gov (United States)

    Schuch, André Passaglia; Yagura, Teiti; Makita, Kazuo; Yamamoto, Hiromasa; Schuch, Nelson Jorge; Agnez-Lima, Lucymara Fassarella; MacMahon, Ricardo Monreal; Menck, Carlos Frederico Martins

    2012-04-01

    Despite growing knowledge on the biological effects of ultraviolet (UV) radiation on human health and ecosystems, it is still difficult to predict the negative impacts of the increasing incidence of solar UV radiation in a scenario of global warming and climate changes. Hence, the development and application of DNA-based biological sensors to monitor the solar UV radiation under different environmental conditions is of increasing importance. With a mind to rendering a molecular view-point of the genotoxic impact of sunlight, field experiments were undertaken with a DNA-dosimeter system in parallel with physical photometry of solar UVB/UVA radiation, at various latitudes in South America. On applying biochemical and immunological approaches based on specific DNA-repair enzymes and antibodies, for evaluating sunlight-induced DNA damage profiles, it became clear that the genotoxic potential of sunlight does indeed vary according to latitude. Notwithstanding, while induction of oxidized DNA bases is directly dependent on an increase in latitude, the generation of 6-4PPs is inversely so, whereby the latter can be regarded as a biomolecular marker of UVB incidence. This molecular DNA lesion-pattern largely reflects the relative incidence of UVA and UVB energy at any specific latitude. Hereby is demonstrated the applicability of this DNA-based biosensor for additional, continuous field experiments, as a means of registering variations in the genotoxic impact of solar UV radiation.

  9. Genotoxic effects induced by the exposure to an environmental mixture of illicit drugs to the zebra mussel.

    Science.gov (United States)

    Parolini, Marco; Magni, Stefano; Castiglioni, Sara; Binelli, Andrea

    2016-10-01

    Despite the growing interest on the presence of illicit drugs in freshwater ecosystems, just recently the attention has been focused on their potential toxicity towards non-target aquatic species. However, these studies largely neglected the effects induced by exposure to complex mixtures of illicit drugs, which could be different compared to those caused by single psychoactive molecules. This study was aimed at investigating the genetic damage induced by a 14-day exposure to a realistic mixture of the most common illicit drugs found in surface waters worldwide (cocaine, benzoylecgonine, amphetamine, morphine and 3,4-methylenedioxymethamphetamine) on the zebra mussel (Dreissena polymorpha). The mixture caused a significant increase of DNA fragmentation and triggered the apoptotic process and micronuclei formation in zebra mussel hemocytes, pointing out its potential genotoxicity towards this bivalve species. PMID:27261879

  10. Application of the comet assay and detection of DNA damage in haemocytes of medicinal leech affected by aluminium pollution: A case study

    International Nuclear Information System (INIS)

    This report describes an investigation of genotoxic effects in medicinal leech (Hirudo verbana) exposed to water and sediment of Lake Njivice (Krk Island, Croatia) contaminated by aluminium compounds. The levels of primary DNA damage in leech haemocytes and loss of DNA integrity caused by acute and chronic exposure to contaminated water and sediment were investigated using the alkaline comet assay. Genotoxic effects induced by acute exposure to contaminants were evaluated on leech haemocytes and blood cells of fish and mouse treated ex vivo. The effects of chronic exposure were assessed on haemocytes sampled from an animal kept under laboratory conditions on contaminated water and sediment for 180 days. The results indicate the DNA damaging potential of aluminium compounds present in an excess amount in tested samples. - The alkaline comet assay applied on Hirudo verbana haemocytes can be a useful tool in determining the potential genotoxicity of water and sediment pollutants.

  11. Application of the comet assay and detection of DNA damage in haemocytes of medicinal leech affected by aluminium pollution: A case study

    Energy Technology Data Exchange (ETDEWEB)

    Mihaljevic, Zlatko, E-mail: zmihalj@biol.pmf.h [Department of Biology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10 000 Zagreb (Croatia); Ternjej, Ivancica, E-mail: ivancica@biol.pmf.h [Department of Biology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10 000 Zagreb (Croatia); Stankovic, Igor, E-mail: igor.stankovic@voda.h [Central Water Management Laboratory, Hrvatske vode, Ulica grada Vukovara 220, 10 000 Zagreb (Croatia); Kerovec, Mladen, E-mail: mkerovec@biol.pmf.h [Department of Biology, Faculty of Science, University of Zagreb, Rooseveltov trg 6, 10 000 Zagreb (Croatia); Kopjar, Nevenka, E-mail: nkopjar@imi.h [Mutagenesis Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, 10 000 Zagreb (Croatia)

    2009-05-15

    This report describes an investigation of genotoxic effects in medicinal leech (Hirudo verbana) exposed to water and sediment of Lake Njivice (Krk Island, Croatia) contaminated by aluminium compounds. The levels of primary DNA damage in leech haemocytes and loss of DNA integrity caused by acute and chronic exposure to contaminated water and sediment were investigated using the alkaline comet assay. Genotoxic effects induced by acute exposure to contaminants were evaluated on leech haemocytes and blood cells of fish and mouse treated ex vivo. The effects of chronic exposure were assessed on haemocytes sampled from an animal kept under laboratory conditions on contaminated water and sediment for 180 days. The results indicate the DNA damaging potential of aluminium compounds present in an excess amount in tested samples. - The alkaline comet assay applied on Hirudo verbana haemocytes can be a useful tool in determining the potential genotoxicity of water and sediment pollutants.

  12. The Comet Assay for the Evaluation of Genotoxic Potential of Landfill Leachate

    Directory of Open Access Journals (Sweden)

    Kamila Widziewicz

    2012-01-01

    Full Text Available Genotoxic assessment of landfill leachate before and after biological treatment was conducted with two human cell lines (Me45 and NHDF and Daphnia magna somatic cells. The alkali version of comet assay was used to examine genotoxicity of leachate by DNA strand breaks analysis and its repair dynamics. The leachate samples were collected from Zabrze landfill, situated in the Upper Silesian Industrial District, Poland. Statistically significant differences (Kruskal-Wallice ANOVA rank model were observed between DNA strand breaks in cells incubated with leachate before and after treatment (P<0.001. Nonparametric Friedman ANOVA confirmed time-reliable and concentration-reliable cells response to leachate concentration. Examinations of chemical properties showed a marked decrease in leachate parameters after treatment which correlate to reduced genotoxicity towards tested cells. Obtained results demonstrate that biological cotreatment of leachate together with municipal wastewater is an efficient method for its genotoxic potential reduction; however, treated leachate still possessed genotoxic character.

  13. Screening potential genotoxic effect of aquatic plant extracts using the mussel micronucleus test

    Institute of Scientific and Technical Information of China (English)

    Bettina Eck-Varanka; Nora Kovts; Katalin Hubai; Gbor Paulovits; rpd Ferincz; Eszter Horvth

    2016-01-01

    Objective:To assess the genotoxic potential of selected aquatic macrophytes:Ceratophyllum demersum L. (hornwort, family Ceratophyllaceae),Typha angustifolia L. (narrowleaf cattail, family Typhaceae),Stratiotes aloides L. (water soldier, family Butomaceae), andOenanthe aquatica (L.) Poir. (water dropwort, family Umbelliferae). Methods: For genotoxicity assessment, the mussel micronucleus test was applied. Micronucleus frequency was determined from the haemolymph ofUnio pictorum L. (painter’s mussel). In parallel, total and hydrolisable tannin contents were determined. Results:All plant extracts elucidated significant mutagenic effect. Significant correlation was determined between tannin content and mutagenic capacity. Conclusions:The significant correlation between genotoxicity as expressed by micronucleus frequency and tannin content (both total and hydrolisable tannins) indicate that tannin is amongst the main compounds being responsible for the genotoxic potential. It might be suggested that genotoxic capacity of these plants elucidate a real ecological effect in the ecosystem.

  14. Genotoxicity of uranium contamination in embryonic zebrafish cells

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Sandrine, E-mail: sandrine.pereira@irsn.fr [Institut de Radioprotection et de Surete Nucleaire (IRSN), DEI, SECRE, LRE, Cadarache (France); Camilleri, Virginie; Floriani, Magali; Cavalie, Isabelle; Garnier-Laplace, Jacqueline; Adam-Guillermin, Christelle [Institut de Radioprotection et de Surete Nucleaire (IRSN), DEI, SECRE, LRE, Cadarache (France)

    2012-03-15

    Uranium is a metal used in the nuclear industry and for military applications. Studies on mammals have shown that uranium is genotoxic. However the molecular and cellular mechanisms responsible for the genotoxicity of uranium are poorly known for other types of vertebrates such as fish. Since unrepaired DNA double-strand breaks (DSBs) are considered to be key lesions in cell lethality, the activity of one of the major DSB-repair pathways, i.e. non-homologous end-joining (NHEJ), has been evaluated in embryonic zebrafish cells (ZF4) exposed to uranium. Genotoxicity of uranium in ZF4 cells was further assessed by comet and micronucleus assays. Exposure to uranium results in the production of DSBs a few hours after incubation. These breaks trigger the phosphorylation of H2AX proteins. We showed that the DNA-PK kinase activity, essential for NHEJ, is altered by the presence of uranium. The presence of uranium in cells disturbs but does not inhibit the repair rate of DSBs. Such a result suggests an impact of uranium upon the reparability of DSBs and the potential activation of alternative DSBs repair pathway leading to the propagation of possible misrepaired DSBs. In parallel, we performed a transmission electron microscopy analysis of cells exposed to uranium and were able to localize internalized uranium using an Energy Dispersive X-ray microanalyser. We observed the formation of precipitates in lysosome-like vesicles for 250 {mu}M of uranium in the medium. The appearance of these precipitates is concomitant with the decrease of the number of DSBs per cell. This process might be a part of a defence system whose role in counteracting cytotoxicity calls for further dedicated research.

  15. Assessment of methyl methacrylate genotoxicity by the micronucleus test

    Directory of Open Access Journals (Sweden)

    Amarildo Mariano de Araújo

    2013-02-01

    Full Text Available The aim of this study was to evaluate the genotoxic potential of methyl methacrylate (MMA vapor by simulating standard occupational exposure of 8 hours per day and using the micronucleus test. We used 32 adult male Wistar rats divided into three groups: A - 16 rats exposed to MMA for 8 hours a day, B - Eight rats receiving single subcutaneous doses of cyclophosphamide on the first day of the experiment (positive control, C - Eight rats receiving only water and food ad libitum (negative control. Eight rats from group A and all of the rats from groups B and C were sacrificed 24 hours after beginning the experiment (acute exposure in group A. The remaining animals in group A were sacrificed 5 days after the experiment began (repeated exposure assessment in group A, simulating occupational exposure 40 hours/week. Femoral bone marrow was collected from each rat at the time of sacrifice for use in the micronucleus test. Two slides were completed per animal and were stained with Giemsa staining. Two thousand polychromatic erythrocytes were counted per animal. The Kruskal-Wallis test followed by a multiple comparisons test (Dunn test was used for statistical analysis. The median number of micronuclei was 7.00 in the group exposed to MMA for 1 day, 2.00 in the group exposed to MMA for 5 days, 9.00 in the group exposed to cyclophosphamide (positive control and 0.756 in the negative control group (p < 0.0001. MMA was genotoxic when measured after 1 day of exposure but was not evidently genotoxic after 5 days.

  16. The urinary bladder carcinogen propoxur does not produce genotoxic effects in the urinary bladder of Wistar male rats.

    Science.gov (United States)

    Iatropoulos, M J; Duan, J-D; Schmuck, G; Williams, G M

    2015-09-01

    Propoxur (PPX) is a carbamate insecticide which induced urinary bladder cancer in Wistar rats when fed at 5000ppm in Altromin 1321 diet (1321). In the present investigation, PPX was studied for induction of several key events related to modes of action (MOA) of carcinogenicity in urinary bladders (UBs). Wistar rats were administered the compound for 28 days at 8000ppm in Provini Liba SA 3883 diet, which is similar to the 1321 diet. o-Anisidine HCl (AH) was used as a genotoxic UB carcinogenic comparator, and trisodium nitrilotriacetate (NTA) as an epigenetic UB carcinogen comparator. Along with the non-dosed control and three test substance groups (PPX, AH, NTA), four more groups were additionally fed 2% ammonium chloride (AC) in the diet to acidify the urine, since 1321 was reported to increase urinary pH. AC did acidify the urine, as expected, although the 3883 diet itself did not increase pH values above 8. In the alkaline comet assay, AH produced DNA single strand breaks (SSBs) in the UB urothelium (UBU) irrespective of AC administration, whereas PPX and NTA did not. In the nucleotide (32)P-postlabeling assay (NPL), AH produced DNA adducts irrespective of AC administration, whereas PPX and NTA did not. Routine (H&E) histopathology evaluation of the UBU did not reveal any hyperplasia or evidence of luminal microprecipitates or calculi in any of the groups. Assessment of UBU proliferation as measured by immunohistochemistry of proliferating cell nuclear antigen, revealed that NTA and NTA plus AC increased the replicating fraction (RF). Also AH plus AC, but not AH alone, increased the RF of UBU, whereas PPX groups were not significantly different from controls. Thus, the results reveal no evidence for DNA SSBs, binding, or alteration of DNA synthesis in the UBU by PPX, while demonstrating UBU DNA damage by AH and showing that NTA does not damage DNA, but causes increased UBU proliferation. The findings are in accord with a genotoxic MOA for AH, and an epigenetic

  17. The urinary bladder carcinogen propoxur does not produce genotoxic effects in the urinary bladder of Wistar male rats.

    Science.gov (United States)

    Iatropoulos, M J; Duan, J-D; Schmuck, G; Williams, G M

    2015-09-01

    Propoxur (PPX) is a carbamate insecticide which induced urinary bladder cancer in Wistar rats when fed at 5000ppm in Altromin 1321 diet (1321). In the present investigation, PPX was studied for induction of several key events related to modes of action (MOA) of carcinogenicity in urinary bladders (UBs). Wistar rats were administered the compound for 28 days at 8000ppm in Provini Liba SA 3883 diet, which is similar to the 1321 diet. o-Anisidine HCl (AH) was used as a genotoxic UB carcinogenic comparator, and trisodium nitrilotriacetate (NTA) as an epigenetic UB carcinogen comparator. Along with the non-dosed control and three test substance groups (PPX, AH, NTA), four more groups were additionally fed 2% ammonium chloride (AC) in the diet to acidify the urine, since 1321 was reported to increase urinary pH. AC did acidify the urine, as expected, although the 3883 diet itself did not increase pH values above 8. In the alkaline comet assay, AH produced DNA single strand breaks (SSBs) in the UB urothelium (UBU) irrespective of AC administration, whereas PPX and NTA did not. In the nucleotide (32)P-postlabeling assay (NPL), AH produced DNA adducts irrespective of AC administration, whereas PPX and NTA did not. Routine (H&E) histopathology evaluation of the UBU did not reveal any hyperplasia or evidence of luminal microprecipitates or calculi in any of the groups. Assessment of UBU proliferation as measured by immunohistochemistry of proliferating cell nuclear antigen, revealed that NTA and NTA plus AC increased the replicating fraction (RF). Also AH plus AC, but not AH alone, increased the RF of UBU, whereas PPX groups were not significantly different from controls. Thus, the results reveal no evidence for DNA SSBs, binding, or alteration of DNA synthesis in the UBU by PPX, while demonstrating UBU DNA damage by AH and showing that NTA does not damage DNA, but causes increased UBU proliferation. The findings are in accord with a genotoxic MOA for AH, and an epigenetic

  18. Genotoxic evaluation of orthodontic bonding adhesives exposed to electron beam irradiation: an in vitro study

    International Nuclear Information System (INIS)

    To evaluate the in vitro genotoxicity of two orthodontic adhesives and to determine the type of cell death they induce on human lymphocytes after exposing to Electron Beam Irradiation. The materials tested were 1. Light cure orthodontic adhesive with conventional primer (Transbond XT3M) and 2. Self cure orthodontic adhesive (Unite, 3M). Cured sterile individual masses were immersed in Phosphate Buffer saline and left at 370℃ for 24 h. Then a volume of 200 μL of the extract medium was mixed with human peripheral blood lymphocyte tested for comet assay by single cell DNA damage assay and apoptosis by DNA diffusion agar assay. The results showed all parameters studied by comet assay were significant (P>0.05). In case of apoptosis, light cure orthodontic adhesive (188.92±55.05) and self cure orthodontic adhesives (255.23±76.43) showed increased diffusion of DNA compared to normal lymphocyte (111.22±8.78). However the level of DNA diffusion was not significantly different between the two adhesives. Light cure orthodontic and self cure orthodontic adhesives were induced apoptosis. Both the adhesives had no significant effect on the percentage of DNA tail and olive tail moment. (author)

  19. Genotoxicity of meso-2,3-dimercapto succinic acid-coated silver sulfide quantum dot

    Directory of Open Access Journals (Sweden)

    Deniz Özkan Vardar

    2015-06-01

    Full Text Available Nanotecnology products have been used in wide applications in chemistry, electronics, energy generation, and medicine. Despite significant interest in developing quantum dots (QDs for biomedical applications, many researchers are convinced that QDs will never be used for the treatment of patients because of their potential toxicity. In various in vitro cell culture studies, the cytotoxic properties of some QD have been demonstrated and they have been suggested to be toxic in humans. In this study, the cytotoxic properties of Ag2S-(Meso-2,3-Dimercapto Succinic acid nanomaterials in V79 cells (Chinese lung fibroblast cell line were determined by MTT assay. The genotoxic effects of Ag2S-(Meso-2,3-Dimercapto Succinic acid were evaluated by the alkaline single cell gel electrophoresis. The cells were treated with Ag2S-(Meso-2,3-Dimercapto Succinic acid at the concentrations of 5- 2000 µg/ml. No cytotoxic effect of Ag2S-(Meso-2,3-Dimercapto Succinic acid at all concentrations studied was observed. No significant increases in DNA damage were found at the studied concentrations when compared to negative control in V79 cells. In conclusion, further in vitro and in vivo studies are required to determine the safety doses of Ag2S-(Meso-2,3-Dimercapto Succinic acid.

  20. Comet assay as a procedure for detecting possible genotoxicity induced by non-ionizing radiation

    Directory of Open Access Journals (Sweden)

    Zsuzsanna Nemeth

    2015-05-01

    In our laboratory we use comet assay for testing genotoxicity of non-ionizing radiation for more than ten years. In the experiments we use whole blood samples (human or dog, cell lines (e.g. H295R cell line or 3 dimensional in vitro skin tissue (epidermis models. In our protocol a slightly modified alkaline Comet assay method of Singh et al. (1988 is used. On our poster there will be presented a brief summary of our experiments with exposure to different types of radiation (ELF, RF, and intermediate frequency. In our protocols the non-ionizing radiation was often combined with ionizing radiation to see whether the non-ionizing radiation can influence the repair of the DNA damage induced by ionizing radiation. For the evaluation of the slides mainly Komet 4.0 image analysis system software (Kinetic Imaging, Liverpool, UK was used, but as we got familiarized with other methods for slide evaluation like grading the comets by visual scoring into 5 categories or the CaspLab software, the comparison of these three methods will be also presented.

  1. Nanoparticles containing allotropes of carbon have genotoxic effects on glioblastoma multiforme cells.

    Science.gov (United States)

    Hinzmann, Mateusz; Jaworski, Sławomir; Kutwin, Marta; Jagiełło, Joanna; Koziński, Rafał; Wierzbicki, Mateusz; Grodzik, Marta; Lipińska, Ludwika; Sawosz, Ewa; Chwalibog, Andrè

    2014-01-01

    The carbon-based nanomaterial family consists of nanoparticles containing allotropes of carbon, which may have a number of interactions with biological systems. The objective of this study was to evaluate the toxicity of nanoparticles comprised of pristine graphene, reduced graphene oxide, graphene oxide, graphite, and ultradispersed detonation diamond in a U87 cell line. The scope of the work consisted of structural analysis of the nanoparticles using transmission electron microscopy, evaluation of cell morphology, and assessment of cell viability by Trypan blue assay and level of DNA fragmentation of U87 cells after 24 hours of incubation with 50 μg/mL carbon nanoparticles. DNA fragmentation was studied using single-cell gel electrophoresis. Incubation with nanoparticles containing the allotropes of carbon did not alter the morphology of the U87 cancer cells. However, incubation with pristine graphene and reduced graphene oxide led to a significant decrease in cell viability, whereas incubation with graphene oxide, graphite, and ultradispersed detonation diamond led to a smaller decrease in cell viability. The results of a comet assay demonstrated that pristine graphene, reduced graphene oxide, graphite, and ultradispersed detonation diamond caused DNA damage and were therefore genotoxic in U87 cells, whereas graphene oxide was not. PMID:24876774

  2. An integrative assessment to determine the genotoxic hazard of estuarine sediments: combining cell and whole-organism responses

    Directory of Open Access Journals (Sweden)

    Pedro M. Costa

    2014-12-01

    Full Text Available The application of the Comet assay in environmental monitoring remains challenging in face of the complexity of environmental stressors, e.g. when dealing with estuarine sediments, that hampers the drawing of cause-effect relationships. Although the in vitro Comet assay may circumvent confounding factors, its application in environmental risk assessment (ERA still needs validation. As such, the present work aims at integrating genotoxicity and oxidative DNA damage induced by sediment-bound toxicants in HepG2 cells with oxidative stress-related effects observed in three species collected from an impacted estuary. Distinct patterns were observed in cells exposed to crude mixtures of sediment contaminants from the urban/industrial area comparatively to the ones from the rural/riverine area of the estuary, with respect to oxidative DNA damage and oxidative DNA damage. The extracts obtained with the most polar solvent and the crude extracts caused the most significant oxidative DNA damage in HepG2 cells, as measured by the FPG (formamidopyrimidine-DNA glycosylase-modified Comet assay. This observation suggests that metals and unknown toxicants more hydrophilic than PAHs may be important causative agents, especially in samples from the rural part of the estuary, where oxidative DNA damage was the most significant. Clams, sole and cuttlefish responded differentially to environmental agents triggering oxidative stress, albeit yielding results accordant with the oxidative DNA damage observed in HepG2 cells. Overall, the integration of in vivo biomarker responses and Comet assay data in HepG2 cells yielded a comparable pattern, indicating that the in vitro FPG-modified Comet assay may be an effective and complementary line-of-evidence in ERA even in particularly challenging, natural, scenarios such as estuarine environments.

  3. Increased DNA damage and oxidative stress among silver jewelry workers.

    Science.gov (United States)

    Aktepe, Necmettin; Kocyigit, Abdurrahim; Yukselten, Yunus; Taskin, Abdullah; Keskin, Cumali; Celik, Hakim

    2015-04-01

    Silver has long been valued as a precious metal, and it is used to make ornaments, jewelry, high-value tableware, utensils, and currency coins. Human exposures to silver and silver compounds can occur oral, dermal, or by inhalation. In this study, we investigated genotoxic and oxidative effects of silver exposure among silver jewelry workers. DNA damage in peripheral mononuclear leukocytes was measured by using the comet assay. Serum total antioxidative status (TAS), total oxidative status (TOS), total thiol contents, and ceruloplasmin levels were measured by using colorimetric methods among silver jewelry workers. Moreover, oxidative stress index (OSI) was calculated. Results were compared with non-exposed healthy subjects. The mean values of mononuclear leukocyte DNA damage were significantly higher than control subjects (p jewelry workers caused oxidative stress and accumulation of severe DNA damage.

  4. Oxidatively damaged DNA in animals exposed to particles

    DEFF Research Database (Denmark)

    Møller, Peter; Danielsen, Pernille Høgh; Jantzen, Kim;

    2013-01-01

    Exposure to combustion-derived particles, quartz and asbestos is associated with increased levels of oxidized and mutagenic DNA lesions. The aim of this survey was to critically assess the measurements of oxidatively damaged DNA as marker of particle-induced genotoxicity in animal tissues....... Publications based on non-optimal assays of 8-oxo-7,8-dihydroguanine by antibodies and/or unrealistically high levels of 8-oxo-7,8-dihydroguanine (suggesting experimental problems due to spurious oxidation of DNA) reported more induction of DNA damage after exposure to particles than did the publications based...... from animal experimental models that both pulmonary and gastrointestinal tract exposure to particles are associated with elevated levels of oxidatively damaged DNA in the lung and internal organs. However, there is a paucity of studies on pulmonary exposure to low doses of particles that are relevant...

  5. Proteomics insights into DNA damage response and translating this knowledge to clinical strategies

    DEFF Research Database (Denmark)

    von Stechow, Louise; Olsen, Jesper V

    2016-01-01

    Genomic instability is a critical driver in the process of cancer formation. At the same time, inducing DNA damage by irradiation or genotoxic compounds constitutes a key therapeutic strategy to kill fast-dividing cancer cells. Sensing of DNA lesions initiates a complex set of signalling pathways...... Spectrometry (MS)-based proteomics emerged as method of choice for global studies of proteins and their posttranslational modifications (PTMs). MS-based studies of the DDR have aided in delineating DNA damage-induced signalling responses. Those studies identified changes in abundance, interactions...... and modification of proteins in the context of genotoxic stress. Here we review ground-breaking MS-based proteomics studies, which analysed changes in protein abundance, protein-protein and protein-DNA interactions, phosphorylation, acetylation, ubiquitylation, SUMOylation and Poly(ADP-ribose)ylation (PARylation...

  6. The Chromatin Scaffold Protein SAFB1 Renders Chromatin Permissive for DNA Damage Signaling

    DEFF Research Database (Denmark)

    Altmeyer, Matthias; Toledo Lazaro, Luis Ignacio; Gudjonsson, Thorkell;

    2013-01-01

    Although the general relevance of chromatin modifications for genotoxic stress signaling, cell-cycle checkpoint activation, and DNA repair is well established, how these modifications reach initial thresholds in order to trigger robust responses remains largely unexplored. Here, we identify...... the chromatin-associated scaffold attachment factor SAFB1 as a component of the DNA damage response and show that SAFB1 cooperates with histone acetylation to allow for efficient γH2AX spreading and genotoxic stress signaling. SAFB1 undergoes a highly dynamic exchange at damaged chromatin in a poly......(ADP-ribose)-polymerase 1- and poly(ADP-ribose)-dependent manner and is required for unperturbed cell-cycle checkpoint activation and guarding cells against replicative stress. Altogether, our data reveal that transient recruitment of an architectural chromatin component is required in order to overcome physiological...

  7. Lymphocyte oxidative stress/genotoxic effects are related to serum IgG and IgA levels in coke oven workers.

    Science.gov (United States)

    Gao, Meili; Li, Yongfei; Zheng, Aqun; Xue, Xiaochang; Chen, Lan; Kong, Yu

    2014-01-01

    We investigated oxidative stress/genotoxic effects levels, immunoglobulin levels, polycyclic aromatic hydrocarbons (PAHs) levels exposed in 126 coke oven workers and in 78 control subjects, and evaluated the association between oxidative stress/genotoxic effects levels and immunoglobulin levels. Significant differences were observed in biomarkers, including 1-hydroxypyrene levels, employment time, percentages of alcohol drinkers, MDA, 8-OHdG levels, CTL levels and CTM, MN, CA frequency, and IgG, IgA levels between the control and exposed groups. Slightly higher 1-OHP levels in smoking users were observed. For the dose-response relationship of IgG, IgA, IgM, and IgE by 1-OHP, each one percentage increase in urinary 1-OHP generates a 0.109%, 0.472%, 0.051%, and 0.067% decrease in control group and generates a 0.312%, 0.538%, 0.062%, and 0.071% decrease in exposed group, respectively. Except for age, alcohol and smoking status, IgM, and IgE, a significant correlation in urinary 1-OHP and other biomarkers in the total population was observed. Additionally, a significant negative correlation in genotoxic/oxidative damage biomarkers of MDA, 8-OH-dG, CTL levels, and immunoglobins of IgG and IgA levels, especially in coke oven workers, was found. These data suggest that oxidative stress/DNA damage induced by PAHs may play a role in toxic responses for PAHs in immunological functions. PMID:25136686

  8. Lymphocyte Oxidative Stress/Genotoxic Effects Are Related to Serum IgG and IgA Levels in Coke Oven Workers

    Directory of Open Access Journals (Sweden)

    Meili Gao

    2014-01-01

    Full Text Available We investigated oxidative stress/genotoxic effects levels, immunoglobulin levels, polycyclic aromatic hydrocarbons (PAHs levels exposed in 126 coke oven workers and in 78 control subjects, and evaluated the association between oxidative stress/genotoxic effects levels and immunoglobulin levels. Significant differences were observed in biomarkers, including 1-hydroxypyrene levels, employment time, percentages of alcohol drinkers, MDA, 8-OHdG levels, CTL levels and CTM, MN, CA frequency, and IgG, IgA levels between the control and exposed groups. Slightly higher 1-OHP levels in smoking users were observed. For the dose-response relationship of IgG, IgA, IgM, and IgE by 1-OHP, each one percentage increase in urinary 1-OHP generates a 0.109%, 0.472%, 0.051%, and 0.067% decrease in control group and generates a 0.312%, 0.538%, 0.062%, and 0.071% decrease in exposed group, respectively. Except for age, alcohol and smoking status, IgM, and IgE, a significant correlation in urinary 1-OHP and other biomarkers in the total population was observed. Additionally, a significant negative correlation in genotoxic/oxidative damage biomarkers of MDA, 8-OH-dG, CTL levels, and immunoglobins of IgG and IgA levels, especially in coke oven workers, was found. These data suggest that oxidative stress/DNA damage induced by PAHs may play a role in toxic responses for PAHs in immunological functions.

  9. Potential genotoxic effects of GSM-1800 exposure on human cutaneous and nerve cells

    International Nuclear Information System (INIS)

    Introduction The GSM-1800 signal has been in use for several years in Europe and questions raised about its potential biological effects, in view of the fact that, with respect to GSM-900, the increase in the carrier frequency corresponds to a more superficial absorption in the tissues. Consequently, the skin becomes an even more important target for the absorption of the radiofrequency radiation (R.F.R.) emitted by mobile phones. Nevertheless, brain tissues remain a critical target. Cells In order to determine whether R.F.R. at 1800 MHz could behave as a genotoxic agent, skin and brain cells were exposed to a 217-Hz-modulated GSM-1800 signal and assayed using the comet assay: (1) normal human epidermal keratinocytes (N.H.E.K.) and dermal fibroblasts (N.H.D.F.) which are cutaneous cells from epidermis and dermis respectively, and (2) the S.H. -S.Y.5.Y. and C.H.M.E.-5 human cell lines, which are neuroblastoma and micro-glial cells, respectively. Exposure The R.F.R. exposure system that was used in these experiments was manufactured by I.T. I.S. (Zurich, Switzerland). It consists in two shorted waveguides allowing to run exposed and sham conditions at the same time in the same culture incubator, at 37 Celsius degrees, 5% CO2. It is controlled by a software, which provides blind conditions until completion of data analysis. The specific absorption rate (S.A.R.) used was 2 W/kg, corresponding to the public exposure limit recommended by I.C.N.I.R.P. and the exposure duration was 48 hours. Comet assay At the end of the exposure, cells were removed from their Petri dish by trypsin/EDTA treatment, counted and 5 x 104 cells were used to detect DNA damage including single DNA breaks. Positive controls were performed using hydrogen peroxidase (1%, 1 hour). The genotoxic effects were detected using the alkaline comet assay kit (Trevigen slides) following the supplier procedure. Under these conditions, 6 independent experiments were performed for each cell type (2 Petri dishes

  10. Assessment of the cytotoxic, genotoxic, and antigenotoxic potential of Pycnogenol® in in vitro mammalian cells.

    Science.gov (United States)

    Taner, Gökçe; Aydın, Sevtap; Aytaç, Zeki; Başaran, Arif Ahmet; Başaran, Nurşen

    2013-11-01

    Pycnogenol® (PYC), a standardized plant extract obtained from the bark of the French maritime pine Pinus pinaster, has been suggested to exert strong antioxidant activity and used as a phytochemical remedy for various diseases. In this study, we investigated the antioxidant capacity of PYC by the trolox equivalent antioxidant capacity (TEAC) assay and the cytotoxicity by neutral red uptake (NRU) test in Chinese Hamster Ovary (CHO) cells. The genotoxic and antigenotoxic effects of PYC were evaluated by the cytokinesis-blocked micronucleus (CBMN) and alkaline comet assays in human peripheral blood lymphocytes. At the concentrations of 2-200 μg/ml, PYC was found to have antioxidant activity. The viability of CHO cells during 24h exposure were not affected at the concentrations of 5-150 μg/ml of PYC. IC50 value of PYC was found to be 285 μg/ml. At the concentrations above 100 μg/ml, PYC alone induced DNA damage and increased MN frequency, although PYC at all concentrations in a dose dependent manner revealed a reduction in the frequency of MN and the extent of DNA damage induced by H2O2. These results suggest PYC might reduce H2O2 induced chromosome breakage and loss and DNA damage in cultured human lymphocytes. PMID:23867543

  11. Studies on Potential Mutagenic and Genotoxic Activity of Setarud

    Directory of Open Access Journals (Sweden)

    B Farzamfar

    2008-09-01

    Full Text Available Background: Setarud (IMODTM is a new herbal drug that has demonstrated immune modulating activity in preliminary investigations. The aim of this study was to evaluate the potential of mutagenicity and genotoxic properties of Setarud following the guidelines of the Organization for Economic Co-operation and Development (OECD for the Testing of Chemicals. Methods: Ames Salmonella/mammalian microsome mutagenesis assay was used to evaluate the ability of the drug and its metabolites to induce mutation in Salmonella tester strains. Setarud was applied in concentrations of 0.1-1000 µg/dish. The effect of the drug metabolites which were formed in the presence of rat liver microsomal fraction S9 was investigated using complete and incomplete microsomal activation mixtures, separately. Induction of dominant lethal mutations in spermatogenic stem cells of male mice was also assessed. Results: In the Ames test, the drug preparation did not cause a significant increase in the number of revertant bacterial colonies as compared with negative control meaning that Setarud within the tested range did not exhibit mutagenic activity. The level of post-implantation losses and as a result the number of lethal mutations in germ cells at different stages of spermatogenesis in mice treated with Setarud was not statistically higher than that of control. Conclusion: Under experimental conditions which were employed, the drug was not mutagenic or genotoxic.

  12. Environmental Nanoparticles Interactions with Plants: Morphological, Physiological, and Genotoxic Aspects

    Directory of Open Access Journals (Sweden)

    C. Remédios

    2012-01-01

    Full Text Available Nanoparticles (NPs are characterized by their small size (less than 100 nm and large surface area, which confer specific physicochemical properties as strength, electrical, and optical features. NPs can be derived from natural or anthropic sources, such as engineered or unwanted/incidental NPs. The composition, dimension, and morphology of engineered NPs enable their use in a variety of areas, such as electronic, biomedical, pharmaceutical, cosmetic, energy, environmental, catalysis, and materials science. As nanotechnology is an innovative and scientific growth area with an exponential production, more information is needed concerning the impacts of these nanomaterials (NMs in the environment and, particularly, in animals/humans health and in plants performance. So, research on NPs as emerging contaminants is therefore a new field in environmental health. This minireview describes, briefly, the NPs characterization and their occurrence in the environment stating air, water, and soil. Finally, particular emphasis is given to the interaction of NPs with plants at different levels: morphology, physiology, and genotoxicity. By analyzing this compiled information, it is evident that research on NPs phytotoxicity is in the beginning, and more comprehensive studies are needed not only on NPs cytotoxicity and genotoxicity but also on the best and the most reliable methods of assessing NPs toxicity.

  13. Antioxidant, genotoxic and antigenotoxic activities of daphne gnidium leaf extracts

    Directory of Open Access Journals (Sweden)

    Chaabane Fadwa

    2012-09-01

    Full Text Available Abstract Background Plants play a significant role in maintaining human health and improving the quality of human life. They serve humans well as valuable components of food, as well as in cosmetics, dyes, and medicines. In fact, many plant extracts prepared from plants have been shown to exert biological activity in vitro and in vivo. The present study explored antioxidant and antigenotoxic effects of Daphne gnidium leaf extracts. Methods The genotoxic potential of petroleum ether, chloroform, ethyl acetate, methanol and total oligomer flavonoid (TOF enriched extracts from leaves of Daphne gnidium, was assessed using Escherichia coli PQ37. Likewise, the antigenotoxicity of the same extracts was tested using the “SOS chromotest test”. Antioxidant activities were studied using non enzymatic and enzymatic method: NBT/Riboflavine and xantine oxidase. Results None of the different extracts produced a genotoxic effect, except TOF extract at the lowest tested dose. Our results showed that D. gnidium leaf extracts possess an antigenotoxic effect against the nitrofurantoin a mutagen of reference. Ethyl acetate and TOF extracts were the most effective in inhibiting xanthine oxidase activity. While, methanol extract was the most potent superoxide scavenger when tested with the NBT/Riboflavine assay. Conclusions The present study has demonstrated that D. gnidium leaf extract possess antioxidant and antigenotoxic effects. These activities could be ascribed to compounds like polyphenols and flavonoid. Further studies are required to isolate the active molecules.

  14. Characterization and genotoxicity evaluation of effluent from a pharmacy industry

    Directory of Open Access Journals (Sweden)

    Hélio Mendes de Oliveira Júnior

    2013-08-01

    Full Text Available The pharmaceutical, textile and food industry bear much of the responsibility for environmental pollution. In order to appropriately treat and mitigate the effects of pharmaceutical effluent, it is necessary to study it in order to determine its physical and chemical composition. In this work, the physicochemical characteristics of a pharmaceutical effluent were studied, to include the concentration of phenolic compounds, heavy metals, total phosphorus, nitrate, chemical oxygen demand (COD, and dissolved oxygen (DO. The in vivo micronucleus test was performed in mice, for investigation and possible genotoxicity and mutagenicity of the effluent from the pharmaceutical hub in Anápolis - Goiás. In all samples, only the phenolics showed concentrations above the values established by CONAMA Resolution 430/2011. The high concentrations of total phenols and synergy between metals found in wastewater can be linked to mutagenicity and genotoxicity found in the effluent, since the results of the micronucleus test indicated higher micronucleus formation when the mice were exposed to the effluent. The results of the study highlighted the necessity of characterizing these effluents in order to determine an appropriate treatment.

  15. Evaluation of genotoxic effect of amalgam restorations in oral cavity

    Directory of Open Access Journals (Sweden)

    Chennoju Sai Kiran

    2015-01-01

    Full Text Available Background: Mercury a popular heavy metal used in dentistry in the form of amalgam is a known clastogen. The assessment of micronuclei in cells is a promising tool for studying the genotoxic effect of mercury on them. Hence, a study was conducted to evaluate the frequency of micronuclei in exfoliated buccal cells of subjects with amalgam restorations. Materials and Methods: A total of 60 subjects (age and gender-matched sample of 30 study group and 30 control group were included in this study. Smears were obtained with moistened wooden spatula from buccal mucosa in close contact with amalgam restoration and fixed with 100% ethyl alcohol. After staining with Papanicolaou stain, all the slides were examined under ×40 and 1,000 cells were counted for the presence of micronuclei. The data were entered into a spread sheet and subjected to statistical analysis. Results: A statistically significant increase in the number of micronuclei containing cells was observed in the study group when compared to control group (P < 0.05. A positive correlation was observed between the duration of restoration and frequency of micronuclei (P < 0.05. Conclusion: The results showed a definite genotoxic effect of amalgam restorations on the oral cavity which can be attributed to the clastogenic action of mercury in amalgam restorations.

  16. Combination of physico-chemical analysis, Allium cepa test system and Oreochromis niloticus erythrocyte based comet assay/nuclear abnormalities tests for cyto-genotoxicity assessments of treated effluents discharged from textile industries.

    Science.gov (United States)

    Hemachandra, Chamini K; Pathiratne, Asoka

    2016-09-01

    Bioassays for cyto-genotoxicity assessments are generally not required in current textile industry effluent discharge management regulations. The present study applied in vivo plant and fish based toxicity tests viz. Allium cepa test system and Oreochromis niloticus erythrocyte based comet assay and nuclear abnormalities tests in combination with physico-chemical analysis for assessing potential cytotoxic/genotoxic impacts of treated textile industry effluents reaching a major river (Kelani River) in Sri Lanka. Of the treated effluents tested from two textile industries, color in the Textile industry 1 effluents occasionally and color, biochemical oxygen demand and chemical oxygen demand in the Textile industry 2 effluents frequently exceeded the specified Sri Lankan tolerance limits for discharge of industrial effluents into inland surface waters. Exposure of A. cepa bulbs to 100% and 12.5% treated effluents from both industries resulted in statistically significant root growth retardation, mito-depression, and induction of chromosomal abnormalities in root meristematic cells in comparison to the dilution water in all cases demonstrating cyto-genotoxicity associated with the treated effluents. Exposure of O. niloticus to the 100% and 12.5% effluents, resulted in erythrocytic genetic damage as shown by elevated total comet scores and induction of nuclear abnormalities confirming the genotoxicity of the treated effluents even with 1:8 dilution. The results provide strong scientific evidence for the crucial necessity of incorporating cyto-genotoxicity impact assessment tools in textile industry effluent management regulations considering human health and ecological health of the receiving water course under chronic exposure. PMID:27209118

  17. Genotoxicity profiles in exfoliated human mammary cells recovered from lactating mothers in Istanbul; relationship with demographic and dietary factors.

    Science.gov (United States)

    Yilmaz, Bayram; Sandal, Suleyman; Ayvaci, Habibe; Tug, Niyazi; Vitrinel, Ayca

    2012-12-12

    We have investigated the presence of DNA damage in human mammary epithelial cells collected from healthy lactating mothers (age, 20-35 years) who were resident in the Istanbul area. Breast milk (10ml) was collected from 30 women between one and two weeks post-partum. Demographic information (parity, breast cancer, occupation, duration of residency in Istanbul, consumption of fish, beef and poultry) was also obtained. Milk samples were diluted 1:1 with RPMI 1640 medium and centrifuged to collect cells. The cells were re-suspended and cell viability was determined by use of 0.4% trypan blue. DNA damage was assessed by use of the comet assay (alkaline single-cell gel electrophoresis). Fifty cells per slide and two slides per sample were scored to evaluate DNA damage. The cells were visually classified into four categories on the basis of extent of migration: undamaged (UD), lightly damaged (LD), moderately damaged (MD) and highly damaged (HD). Total comet scores (TCS) were calculated as: 1× UD+2× LD+3× MD+4× HD. Exfoliated mammary cells of the donors showed high (TCS≥150a.u.), moderate and low DNA damage in 10 (33.3%), 8 (26.7%) and 12 (40%) mothers, respectively. There was no significant correlation between TCS for DNA damage and the duration of previous breastfeeding, parity or age. None of the mothers was vegetarian, smoker or on any medication. Meat and chicken consumption did not significantly correlate with the TCS values. Fish consumption was significantly correlated with TCS results (Spearman's rho=0.39, p<0.05). No significant correlation was found between the DNA-damage scores and the period of residency in Istanbul, but fish consumption increased as the duration of stay was longer (Spearman's rho=0.53, p<0.01). These findings suggest that the primary causes of differences in genotoxicity detected in lactating mothers in Istanbul may be of dietary origin. Our experience also confirms that sampling breast milk from lactating mothers provides a valuable

  18. Effects of smoking during pregnancy on DNA damage and ROS level consequences in maternal and newborns’ blood.

    Science.gov (United States)

    Aydogan, Umit; Durmaz, Emre; Ercan, Cihangir Mutlu; Eken, Ayse; Ulutas, Onur Kenan; Kavuk, Serkan; Gursel, Orhan; Alanbay, Ibrahim; Akay, Cemal; Kurekci, Ahmet Emin; Aydin, Ahmet; Sayal, Ahmet; Saglam, Kenan; Cok, Ismet

    2013-01-01

    Some of the genotoxic/carcinogenic substances or metabolites in cigarette smoke are capable of passing through the placenta and harming a newborn’s health. Smoking is also known as a factor in the formation of oxidative damage and the main mechanism involved in the carcinogenic process. Predetermining this genotoxic risk can be successfully achieved by measuring certain parameters of oxidative stress. The comet assay is considered an important biomarker for the evaluation of genotoxic substances and is effective for detecting DNA damage caused by smoking. This study examined third trimester bloods and the cord blood of 28 actively smoking and 22 non-smoking mothers in terms of DNA damage and oxidative stress parameters. Cu/Zn superoxide dismutase (CuZn-SOD), malondialdehyde (MDA), catalase (CAT), plasma nitrite/nitrates (NO2-/NO3-), selenium-dependent glutathione peroxidase (Se-GPx), Cu, and Zn levels were measured as indicators of oxidative damage. There were no significant increases in DNA damage of the actively smoking pregnant group in comparison with the non-smoking pregnant group, either in the third trimester or cord blood. Oxidative stress parameters of smoker and non-smoker groups were statistically different for MDA (pSmoking mothers may have been exposed to more oxidative stress than non-smoking mothers

  19. Comparative embryotoxicity and genotoxicity of the herbicide diuron and its metabolites in early life stages of Crassostrea gigas: Implication of reactive oxygen species production.

    Science.gov (United States)

    Behrens, Daphné; Rouxel, Julien; Burgeot, Thierry; Akcha, Farida

    2016-06-01

    ). Concerning genotoxicity, no significant difference was observed between diuron and all of its metabolites including 3, 4 DCA with damages detected from the concentration of 0.05μgL(-1). As for diuron, the toxicity of the metabolites seems to be mediated in some part by ROS production as clearly demonstrated by the decrease in genotoxicity and developmental abnormalities in the presence of the oxidant scavenger, ascorbic acid. PMID:27078212

  20. The cadmium–mercaptoacetic acid complex contributes to the genotoxicity of mercaptoacetic acid-coated CdSe-core quantum dots

    Directory of Open Access Journals (Sweden)

    Tang WK

    2012-05-01

    Full Text Available Weikun Tang,1 Junpeng Fan,1 Yide He,1 Bihai Huang,2 Huihui Liu,1 Daiwen Pang,2 Zhixiong Xie11College of Life Sciences, 2College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, People's Republic of ChinaAbstract: Quantum dots (QDs have many potential clinical and biological applications because of their advantages over traditional fluorescent dyes. However, the genotoxicity potential of QDs still remains unclear. In this paper, a plasmid-based system was designed to explore the genotoxic mechanism of QDs by detecting changes in DNA configuration and biological activities. The direct chemicobiological interactions between DNA and mercaptoacetic acid-coated CdSe-core QDs (MAA–QDs were investigated. After incubation with different concentrations of MAA–QDs (0.043, 0.13, 0.4, 1.2, and 3.6 µmol/L in the dark, the DNA conversion of the covalently closed circular (CCC DNA to the open circular (OC DNA was significantly enhanced (from 13.9% ± 2.2% to 59.9% ± 12.8% while the residual transformation activity of plasmid DNA was greatly decreased (from 80.7% ± 12.8% to 13.6% ± 0.8%, which indicated that the damages to the DNA structure and biological activities induced by MAA–QDs were concentration-dependent. The electrospray ionization mass spectrometry data suggested that the observed genotoxicity might be correlated with the cadmium–mercaptoacetic acid complex (Cd–MAA that is formed in the solution of MAA–QDs. Circular dichroism spectroscopy and transformation assay results indicated that the Cd–MAA complex might interact with DNA through the groove-binding mode and prefer binding to DNA fragments with high adenine and thymine content. Furthermore, the plasmid transformation assay could be used as an effective method to evaluate the genotoxicities of nanoparticles.Keywords: genotoxicity, MAA CdSe quantum dots, cadmium–MAA complex, transformation assay, DNA 

  1. Smac/DIABLO Promotes Mitomycin C-induced Apoptosis of Bladder Cancer T24 Cells

    Institute of Scientific and Technical Information of China (English)

    WANG Liang; ZENG Fuqing; ZHENG Liduan; TONG Qiangsong

    2006-01-01

    The enhancing effects of Smac gene on the mitomycin C-induced apoptosis of the bladder cancer cell line T24 were investigated. The Smac gene was transfected into bladder cancer cell line T24 under the induction of liposome. The intrinsic Smac level was detected by using immunohistochemistry and RT-PCR. The in vitro cellular growth activities were assayed by MTT colorimetry.Apoptosis was assayed by the flow cytometry. The results showed that as compared with the control cells, the apoptosis rate of T24 cells induced by mitomycin C was enhanced by transfected Smac gene. Flow cytometry revealed that, the apoptosis rate was 18.84% and 33.52%, and 10.72% and 26.24% respectively in blank and transfected cells treated with 0.05 or 0.005 mg/mL mitomycin C (P<0.05). It was concluded that Smac could enhance the apoptosis of T24 by mitomycin C,which could provide a useful experimental evidence for bladder cancer therapy.

  2. DNA damage in organs of mice treated acutely with patulin, a known mycotoxin.

    Science.gov (United States)

    de Melo, Flávia Terezinha; de Oliveira, Iuri Marques; Greggio, Samuel; Dacosta, Jaderson Costa; Guecheva, Temenouga Nikolova; Saffi, Jenifer; Henriques, João Antonio Pêgas; Rosa, Renato Moreira

    2012-10-01

    Patulin, a known mycotoxin, is considered a significant contaminant in apples, apple-derived products and feeds. This study investigated the genotoxic effects of patulin in multiple organs (brain, kidney, liver and urinary bladder) of mice using an in vivo comet assay. We assessed the mechanism underlying this genotoxicity by measuring the GSH content and the thiobarbituric acid-reactive species (TBARS) level. Male CF-1 mice were given 1.0-3.75 mg/kg patulin intraperitoneally. The effect of patulin was dose-dependent and the highest patulin dose induced DNA strand breaks in the brain (damage index, DI, in hippocampus increased from 36.2 in control animals to 127.5), liver (44.3-138.4) and kidneys (31.5-99); decreased levels of GSH (hippocampus--from 46.9 to 18.4 nmol/mg protein); and an increase in lipid peroxidation (hippocampus--from 5.8 to 20.3 MDA equivalents/mg protein). This finding establishes an interrelationship between the pro-oxidant and genotoxic effects of patulin. Pre-treatment administration of N-acetyl-cysteine reduced patulin-induced DNA damage (hippocampus--DI from 127.5 to 39.8) and lipid peroxidation (hippocampus--20.3 to 12.8 MDA equivalents/mg protein) by restoring cellular GSH levels, reinforcing the positive relationship between patulin-induced GSH depletion and DNA damage caused by systemic administration of this mycotoxin. PMID:22222931

  3. Dietary modulation of the biotransformation and genotoxicity of aflatoxin B(1).

    Science.gov (United States)

    Gross-Steinmeyer, Kerstin; Eaton, David L

    2012-09-28

    Diet and its various components are consistently identified as among the most important 'risk factors' for cancer worldwide, yet great uncertainty remains regarding the relative contribution of nutritive (e.g., vitamins, calories) vs. non-nutritive (e.g., phytochemicals, fiber, contaminants) factors in both cancer induction and cancer prevention. Among the most potent known human dietary carcinogens is the mycotoxin, aflatoxin B(1) (AFB). AFB and related aflatoxins are produced as secondary metabolites by the molds Aspergillus flavus and Aspergillus parasiticus that commonly infect poorly stored foods including peanuts, pistachios, corn, and rice. AFB is a potent hepatocarcinogenic agent in numerous animal species, and has been implicated in the etiology of human hepatocellular carcinoma. Recent research has shown that many diet-derived factors have great potential to influence AFB biotransformation, and some efficiently protect from AFB-induced genotoxicity. One key mode of action for reducing AFB-induced carcinogenesis in experimental animals was shown to be the induction of detoxification enzymes such as certain glutathione-S-transferases that are regulated through the Keap1-Nrf2-ARE signaling pathway. Although initial studies utilized the dithiolthione drug, oltipraz, as a prototypical inducer of antioxidant response, dietary components such as suforaphane (SFN) are also effective inducers of this pathway in rodent models. However, human GSTs in general do not appear to be extensively induced by SFN, and GSTM1 - the only human GST with measurable catalytic activity toward aflatoxin B(1)-8,9-epoxide (AFBO; the genotoxic metabolite of AFB), does not appear to be induced by SFN, at least in human hepatocytes, even though its expression in human liver cells does appear to offer considerable protection against AFB-DNA damage. Although induction of detoxification pathways has served as the primary mechanistic focus of chemoprevention studies, protective effects of

  4. Dietary modulation of the biotransformation and genotoxicity of aflatoxin B1

    International Nuclear Information System (INIS)

    Diet and its various components are consistently identified as among the most important ‘risk factors’ for cancer worldwide, yet great uncertainty remains regarding the relative contribution of nutritive (e.g., vitamins, calories) vs. non-nutritive (e.g., phytochemicals, fiber, contaminants) factors in both cancer induction and cancer prevention. Among the most potent known human dietary carcinogens is the mycotoxin, aflatoxin B1 (AFB). AFB and related aflatoxins are produced as secondary metabolites by the molds Aspergillus flavus and Aspergillus parasiticus that commonly infect poorly stored foods including peanuts, pistachios, corn, and rice. AFB is a potent hepatocarcinogenic agent in numerous animal species, and has been implicated in the etiology of human hepatocellular carcinoma. Recent research has shown that many diet-derived factors have great potential to influence AFB biotransformation, and some efficiently protect from AFB-induced genotoxicity. One key mode of action for reducing AFB-induced carcinogenesis in experimental animals was shown to be the induction of detoxification enzymes such as certain glutathione-S-transferases that are regulated through the Keap1–Nrf2–ARE signaling pathway. Although initial studies utilized the dithiolthione drug, oltipraz, as a prototypical inducer of antioxidant response, dietary components such as suforaphane (SFN) are also effective inducers of this pathway in rodent models. However, human GSTs in general do not appear to be extensively induced by SFN, and GSTM1 – the only human GST with measurable catalytic activity toward aflatoxin B1-8,9-epoxide (AFBO; the genotoxic metabolite of AFB), does not appear to be induced by SFN, at least in human hepatocytes, even though its expression in human liver cells does appear to offer considerable protection against AFB–DNA damage. Although induction of detoxification pathways has served as the primary mechanistic focus of chemoprevention studies, protective

  5. Variation in genotoxic susceptibility and biomarker responses in Cirrhinus mrigala and Catla catla from different ecological niches of the Chenab River.

    Science.gov (United States)

    Hussain, Bilal; Sultana, Tayyaba; Sultana, Salma; Mahboob, Shahid; Al-Ghanim, K A; Nadeem, Shahid

    2016-07-01

    A large number of methods have been applied to evaluate genotoxic damage in different aquatic species. Comet assay, as a method for detecting DNA alterations, and micronucleus test, as an index of chromosomal damage are the most widely used and authentic methods in laboratory and field studies. The primary objective of the study was to evaluate the genotoxic effects of heavy metals generated by toxic industrial effluents and various kinds of pollutants from urban and agricultural areas and domestic waste on Catla catla and Cirrhinus mrigala due to water pollution in the Chenab River, Pakistan. The heavy metals Cd, Cu, Mn. Zn, Pb, Cr, Sn, and Hg were detected by atomic absorption spectrophotometry from water samples collected from predetermined sampling sites. All the physicochemical parameters and heavy metals were found to exceed the upper limits recommended by various agencies. Comet assays showed significant (p  0.05) findings were observed between fish collected from farmed and non-polluted upstream waters. Micronucleus assays showed similar findings for single and double micronucleus induction in C. catla and C. mrigala. A significantly (p comet and micronucleus assays, expedient methods for toxicity screening of aquatic environments. Regular monitoring is necessary to assess eco-health of the Chenab River by choosing perhaps C. mrigala, being a bottom feeder, as a bioindicator that could provide more reliable information to determine the status of the environmental quality of the river. PMID:27068917

  6. Physico-chemical characteristics and cyto-genotoxic potential of ZnO and TiO{sub 2} nanoparticles on human colon carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Barone, F; Bizzarri, L; Andreoli, C; Zijno, A; De Angelis, I [Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome (Italy); De Berardis, B [Department of Technology and Health, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Degan, P, E-mail: barone@iss.it [Molecular Mutagenesis and DNA Repair, Istituto Nazionale per la Ricerca sul Cancro, L.go R. Benzi 10, 16132 Genova (Italy)

    2011-07-06

    The aim of the present study is to investigate the role of the physico-chemical properties of ZnO and TiO{sub 2} NPs in the potential cytotoxicity, genotoxicity and oxidative DNA damage induction on Caco-2 cell line. As negative control, fine TiO{sub 2} particles were used. The characterization of particles was carried out by electron microscopy (SEM, TEM) using a Soft Imaging System. To evaluate the effects of ZnO and TiO{sub 2} NPs induced on Caco-2 viability, Neutral Red assay was performed after treatment with different particle concentrations. Our results showed a significant dose and time dependent effect after treatment with ZnO NPs. On the contrary, no effect was observed on Caco-2 cells exposed to TiO{sub 2} particles either in micro-and in nano-size. The role of surface in the cytotoxicity induced on Caco-2 was also considered. The levels of DNA 8-oxodG, as the main marker of oxidative DNA damage, were measured by high-performance liquid chromatography with electrochemical detection (HPLC/EC). A significant increase in the 8-oxodG levels was observed after 6 h exposure for both NPs. The estimation of the potential genotoxicity of the two NPs is ongoing by the cytokinesis-block micronucleus assay. Our preliminary results showed that a slight micronucleus increase in binucleated cells was detected in the dose range applied only for ZnO.

  7. Genotoxic hazards of azo pigments and other colorants related to 1-phenylazo-2-hydroxynaphthalene.

    Science.gov (United States)

    Møller, P; Wallin, H

    2000-01-01

    Azo pigments are used extensively as coloring agents in inks, paints and cosmetics. We have surveyed the literature for genotoxic and cancer data on nine colorants, which are structurally related to 1-phenylazo-2-hydroxynaphthalene (C.I. Solvent yellow 14). C.I. Solvent yellow 14 is metabolized by oxidative and peroxidative enzymes. Metabolically activated C.I. Solvent yellow 14 forms both RNA and DNA adducts. It induces liver nodules in rats upon oral administration. Although there is a mixture of negative and positive findings in short-term tests and in animal cancer studies, C.I. Solvent yellow 14 should be considered genotoxic. C.I. Pigment red 3 should be considered carcinogenic but is only weakly genotoxic. C.I. Solvent yellow 7, C.I. Pigment orange 5, C.I. Pigment red 4, and C.I. Pigment red 23 should be considered genotoxic. C.I. Pigment red 53:1 is not genotoxic, and observations of spleen tumors in male rats but not in female rats or mice seem to be related to toxic effects of high doses of C.I. Pigment red 53:1 in this organ. The data in the literature indicate that Pigment red 57:1 is not genotoxic or carcinogenic. We did not find sufficient data for a relevant evaluation of C.I. Pigment red 2 and C.I. Pigment red 64:1. Some of the colorants have in common the 2-amino-1-naphthol structure. This compound is not genotoxic. On the other hand, reductive cleavage of the azo bonds or hydrolysis of anilido bonds would produce aromatic amines, most of which have been under suspicion for genotoxicity or carcinogenicity. For C.I. Pigment red 53:1 and 57:1, sulphonated aromatic amines would be formed that are not genotoxic.

  8. The nucleotide excision repair pathway is required for UV-C-induced apoptosis in Caenorhabditis elegans.

    Science.gov (United States)

    Stergiou, L; Doukoumetzidis, K; Sendoel, A; Hengartner, M O

    2007-06-01

    Ultraviolet (UV) radiation is a mutagen of major clinical importance in humans. UV-induced damage activates multiple signaling pathways, which initiate DNA repair, cell cycle arrest and apoptosis. To better understand these pathways, we studied the responses to UV-C light (254 nm) of germ cells in Caenorhabditis elegans. We found that UV activates the same cellular responses in worms as in mammalian cells. Both UV-induced apoptosis and cell cycle arrest were completely dependent on the p53 homolog CEP-1, the checkpoint proteins HUS-1 and CLK-2, and the checkpoint kinases CHK-2 and ATL-1 (the C. elegans homolog of ataxia telangiectasia and Rad3-related); ATM-1 (ataxia telangiectasia mutated-1) was also required, but only at low irradiation doses. Importantly, mutation of genes encoding nucleotide excision repair pathway components severely disrupted both apoptosis and cell cycle arrest, suggesting that these genes not only participate in repair, but also signal the presence of damage to downstream components of the UV response pathway that we delineate here. Our study suggests that whereas DNA damage response pathways are conserved in metazoans in their general outline, there is significant evolution in the relative importance of individual checkpoint genes in the response to specific types of DNA damage.

  9. Acute toxicity and genotoxic activity of avocado seed extract (Persea americana Mill., c.v. Hass).

    Science.gov (United States)

    Padilla-Camberos, Eduardo; Martínez-Velázquez, Moisés; Flores-Fernández, José Miguel; Villanueva-Rodríguez, Socorro

    2013-01-01

    The use of vegetal extracts requires toxicological and genotoxic evaluations to establish and verify safety before being added to human cosmetic, pharmaceutical medicine, or alimentary products. Persea americana seeds have been used in traditional medicine as treatment for several diseases. In this work, the ethanolic seed extract of Persea americana was evaluated with respect to its genotoxic potential through micronucleus assay in rodents. The frequency of micronuclei in groups of animals treated with avocado seed extract showed no differences compared to the negative control (vehicle); therefore, it is considered that the avocado seed extract showed no genotoxic activity in the micronucleus test.

  10. Acute Toxicity and Genotoxic Activity of Avocado Seed Extract (Persea americana Mill., c.v. Hass

    Directory of Open Access Journals (Sweden)

    Eduardo Padilla-Camberos

    2013-01-01

    Full Text Available The use of vegetal extracts requires toxicological and genotoxic evaluations to establish and verify safety before being added to human cosmetic, pharmaceutical medicine, or alimentary products. Persea americana seeds have been used in traditional medicine as treatment for several diseases. In this work, the ethanolic seed extract of Persea americana was evaluated with respect to its genotoxic potential through micronucleus assay in rodents. The frequency of micronuclei in groups of animals treated with avocado seed extract showed no differences compared to the negative control (vehicle; therefore, it is considered that the avocado seed extract showed no genotoxic activity in the micronucleus test.

  11. Acute toxicity and genotoxic activity of avocado seed extract (Persea americana Mill., c.v. Hass).

    Science.gov (United States)

    Padilla-Camberos, Eduardo; Martínez-Velázquez, Moisés; Flores-Fernández, José Miguel; Villanueva-Rodríguez, Socorro

    2013-01-01

    The use of vegetal extracts requires toxicological and genotoxic evaluations to establish and verify safety before being added to human cosmetic, pharmaceutical medicine, or alimentary products. Persea americana seeds have been used in traditional medicine as treatment for several diseases. In this work, the ethanolic seed extract of Persea americana was evaluated with respect to its genotoxic potential through micronucleus assay in rodents. The frequency of micronuclei in groups of animals treated with avocado seed extract showed no differences compared to the negative control (vehicle); therefore, it is considered that the avocado seed extract showed no genotoxic activity in the micronucleus test. PMID:24298206

  12. Evaluation of the co-genotoxic effects of 1800 MHz GSM radiofrequency exposure and a chemical mutagen in cultured human cells

    Science.gov (United States)

    Perrin, Anne; Freire, Maëlle; Bachelet, Christine; Collin, Alice; Levêque, Philippe; Pla, Simon; Debouzy, Jean-Claude

    2010-11-01

    We investigated the effect of a 1800 MHz radiofrequency GSM signal combined with a known chemical mutagen (4-nitroquinoline-N-oxide: 4NQO) on human THP1 cells. Comet and γ-H2AX assays were used to assess DNA damage. No heating of the cell cultures was noted during exposure (2 h). The exposure of cells to electromagnetic fields with SARs of 2 to 16 W/kg did not increase the DNA damage induced by 4NQO, whereas the number of DNA strand breaks increased with a temperature increase of at least 4 °C. In conclusion, no co-genotoxic effect of radiofrequency was found at levels of exposure that did not induce heating.

  13. Assessment of phenolic content, free-radical-scavenging capacity genotoxic and anti-genotoxic effect of aqueous extract prepared from Moricandia arvensis leaves.

    Science.gov (United States)

    Skandrani, I; Limem, I; Neffati, A; Boubaker, J; Ben Sghaier, M; Bhouri, W; Bouhlel, I; Kilani, S; Ghedira, K; Chekir-Ghedira, L

    2010-02-01

    The present study was undertaken to provide a set of data on the safety of an aqueous extract (AQE) from Moricandia arvensis. For this reason, Escherichia coli tested strains PQ35 and PQ37 were used to detect induction of DNA lesions by AQE. The SOS Chromotest showed that AQE induced a marginally genotoxic effect, as expressed by the induction factor (IF) value only with E. coli PQ37 tested strain (IF=1.77 at a dose of 250 microg/assay). The measurement of the anti-genotoxic activity of the AQE was also studied by inhibition of beta-galactosidase induction. A significant anti-genotoxic effect was observed with different tested doses of AQE, which suggests that M. arvensis extract has the potential to protect DNA from the action of nitrofurantoïn (NF) and free radicals generated by hydrogen peroxide (H2O2). In addition to anti-genotoxic activity, AQE showed a free-radical-scavenging capacity towards ABTS+* and DPPH*. Total phenolic content was also evaluated following Folin-Ciocalteu method and results indicated high correlation between total phenol content and anti-genotoxic and antioxidant activities for AQE, but the highest correlation was showed with its capacity to stabilize ABTS+* (R2=0.9944). PMID:19951736

  14. Genotoxic Effects of Low- and High-LET Radiation on Human Epithelial Cells Grown in 2-D Versus 3-D Culture

    Science.gov (United States)

    Patel, Z. S.; Cucinotta, F. A.; Huff, J. L.

    2011-01-01

    Risk estimation for radiation-induced cancer relies heavily on human epidemiology data obtained from terrestrial irradiation incidents from sources such as medical and occupational exposures as well as from the atomic bomb survivors. No such data exists for exposures to the types and doses of high-LET radiation that will be encountered during space travel; therefore, risk assessment for space radiation requires the use of data derived from cell culture and animal models. The use of experimental models that most accurately replicate the response of human tissues is critical for precision in risk projections. This work compares the genotoxic effects of radiation on normal human epithelial cells grown in standard 2-D monolayer culture compared to 3-D organotypic co-culture conditions. These 3-D organotypic models mimic the morphological features, differentiation markers, and growth characteristics of fully-differentiated normal human tissue and are reproducible using defined components. Cultures were irradiated with 2 Gy low-LET gamma rays or varying doses of high-LET particle radiation and genotoxic damage was measured using a modified cytokinesis block micronucleus assay. Our results revealed a 2-fold increase in residual damage in 2 Gy gamma irradiated cells grown under organotypic culture conditions compared to monolayer culture. Irradiation with high-LET particle radiation gave similar results, while background levels of damage were comparable under both scenarios. These observations may be related to the phenomenon of "multicellular resistance" where cancer cells grown as 3-D spheroids or in vivo exhibit an increased resistance to killing by chemotherapeutic agents compared to the same cells grown in 2-D culture. A variety of factors are likely involved in mediating this process, including increased cell-cell communication, microenvironment influences, and changes in cell cycle kinetics that may promote survival of damaged cells in 3-D culture that would

  15. Genotoxicity of paracetamol on the germ cells of Drosophilla melanogaster

    Directory of Open Access Journals (Sweden)

    Saleha Y. M. alakilli

    2007-12-01

    Full Text Available Paracetamol is a common analgesic and antipyretic drug. The aim of the present study is to determine the potential genetic effects of Paracetamol in Drosophilla melanogaster using two methods: Sex Linked Recessive Lethals (SLRL test and effect of Paracetamol on enzyme activity using spectrophotometric analysis. Three concentrations of drug were used (5, 10, and 20 mM. The results reveal significant differences in S.L.R.L, except spermatozoa stages showed insignificant increases when the data of the four broods were considered all together in three treatments. Meanwhile, Paracetamol showed a genotoxic effects in the three categories of the two generations of S.L.R.L, F1 heterozygous females, F2 bar eye females and F2 wild type males on the genetic back ground of Cholinesterase in all treatments.

  16. Genotoxicity Studies in Groundwater, Surface Waters, and Contaminated Soil

    Directory of Open Access Journals (Sweden)

    Luc Verschaeve

    2002-01-01

    Full Text Available It is at present considered important to include biological tests in measuring programmes of environmental samples to supplement the chemical and physical parameters that are currently used. A battery of tests is therefore necessary, also within a given “endpoint” (e.g., genotoxicity, because one single test will not give all the answers to our questions. As it is not possible to include all available tests in routine screening programmes, a selection of tests should be made. According to comparative investigations, the bacterial Ames test remains very important. When no preconcentration step is involved, other bacterial tests (e.g., the umu-C and VITOTOX® tests may be recommended. The comet assay may be used in Daphnia or human white blood cells. Further validations, comparisons, mechanistic investigations, etc. remain necessary as differences are often found between the tests that are not solely explained by differences in genetic endpoint and that therefore should further be investigated and understood.

  17. Effects of wood dust:Inflammation, Genotoxicity and Cancer

    DEFF Research Database (Denmark)

    Lange, Jette Bornholdt

    The present thesis focuses on the inflammatory, genotoxic and carcinogenic effects of exposure to different species of wood dust. The experimental work performed in this thesis consists of two parts. The first part of the study was carried out in an in vitro model with the human lung epithelial...... with incidence rates between of 0.3 to 1.4 per 100,000 for men and 0.1 to 0.8 per 100,000 for women in Europe, depending on country. However, cancer at this site is associated with occupational exposures including wood dust. Especially the adenocarcinoma subtype is strongly associated with exposure to wood dust...... primarily from hard woods. Non-malignant symptoms like allergy, asthma, rhinitis and chronic bronchitis have also been associated with occupational exposure to wood dust in epidemiological studies. In most epidemiological studies hardwoods (e.g. oak and beech wood dust) seems to have greater association...

  18. Subchronic exposure to ethyl tertiary butyl ether resulting in genetic damage in Aldh2 knockout mice.

    Science.gov (United States)

    Weng, Zuquan; Suda, Megumi; Ohtani, Katsumi; Mei, Nan; Kawamoto, Toshihiro; Nakajima, Tamie; Wang,