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Sample records for cathartic colon genotoxicity

  1. Is Senna Laxative Use Associated to Cathartic Colon, Genotoxicity, or Carcinogenicity?

    Directory of Open Access Journals (Sweden)

    M. A. Morales

    2009-01-01

    Full Text Available Due to their natural origin, apparent low oral toxicity, effectiveness, and accessibility without a medical prescription, the anthranoid laxatives are a popular remedy for constipation and are frequently used abusively. Therefore, it is important to characterize its harmful and/or toxic effects. The sennosides, main active metabolites of senna, exhibit a very low toxicity in rats, and its genotoxic activity in bacterial strains as well as mammal cells was classified as weak in those cases where it was shown to be significant. The toxicological and mutagenic status of the crude extract of senna, however, is not as well characterized, and it is necessary to do so since it is frequently, and at the same time incorrectly, believed that the chronic use of anthranoid laxatives is a risk factor for the development of colorectal cancer. The objective of this article was to review the information that arises in various scientific medical databases using key words such as senna, sen, Senna alexandrina, Cassia angustifolia, sennosides, laxative toxicity, mainly ISI and non-ISI articles of journals with an editorial committee. Web pages of products or companies that publicize or commercialize this type of laxative were not included. This analysis establishes that (1 there is no convincing evidence that the chronic use of senna has, as a consequence, a structural and/or functional alteration of the enteric nerves or the smooth intestinal muscle, (2 there is no relation between long-term administration of a senna extract and the appearance of gastrointestinal tumors or any other type in rats, (3 senna is not carcinogenic in rats even after a two-year daily dose of up to 300 mg/kg/day, and (4 the current evidence does not show that there is a genotoxic risk for patients who take laxatives containing senna extracts or sennosides.

  2. Is senna laxative use associated to cathartic colon, genotoxicity, or carcinogenicity?

    Science.gov (United States)

    Morales, M A; Hernández, D; Bustamante, S; Bachiller, I; Rojas, A

    2009-01-01

    Due to their natural origin, apparent low oral toxicity, effectiveness, and accessibility without a medical prescription, the anthranoid laxatives are a popular remedy for constipation and are frequently used abusively. Therefore, it is important to characterize its harmful and/or toxic effects. The sennosides, main active metabolites of senna, exhibit a very low toxicity in rats, and its genotoxic activity in bacterial strains as well as mammal cells was classified as weak in those cases where it was shown to be significant. The toxicological and mutagenic status of the crude extract of senna, however, is not as well characterized, and it is necessary to do so since it is frequently, and at the same time incorrectly, believed that the chronic use of anthranoid laxatives is a risk factor for the development of colorectal cancer. The objective of this article was to review the information that arises in various scientific medical databases using key words such as senna, sen, Senna alexandrina, Cassia angustifolia, sennosides, laxative toxicity, mainly ISI and non-ISI articles of journals with an editorial committee. Web pages of products or companies that publicize or commercialize this type of laxative were not included. This analysis establishes that (1) there is no convincing evidence that the chronic use of senna has, as a consequence, a structural and/or functional alteration of the enteric nerves or the smooth intestinal muscle, (2) there is no relation between long-term administration of a senna extract and the appearance of gastrointestinal tumors or any other type in rats, (3) senna is not carcinogenic in rats even after a two-year daily dose of up to 300 mg/kg/day, and (4) the current evidence does not show that there is a genotoxic risk for patients who take laxatives containing senna extracts or sennosides.

  3. The safety of osmotically acting cathartics in colonic cleansing

    DEFF Research Database (Denmark)

    Nyberg, Caroline; Hendel, J.; Nielsen, O.H.

    2010-01-01

    Efficient cleansing of the colon before a colonoscopy or a radiological examination is essential. The osmotically acting cathartics (those given the Anatomical Therapeutic Chemical code A06AD) currently used for this purpose comprise products based on three main substances: sodium phosphate......, combinations of polyethylene glycol and electrolyte lavage solutions (PEG-ELS), and magnesium citrate. All these preparations give adequate cleansing results and have similar profiles in terms of the frequency and type of mild to moderate adverse effects. However, serious adverse events, such as severe...... hyperphosphatemia and irreversible kidney damage owing to acute phosphate nephropathy, have been reported after use of sodium-phosphate-based products. The aim of this Review is to provide an update on the potential safety issues related to the use of osmotically acting cathartics, especially disturbances of renal...

  4. The safety of osmotically acting cathartics in colonic cleansing

    DEFF Research Database (Denmark)

    Nyberg, Caroline; Hendel, J.; Nielsen, O.H.

    2010-01-01

    hyperphosphatemia and irreversible kidney damage owing to acute phosphate nephropathy, have been reported after use of sodium-phosphate-based products. The aim of this Review is to provide an update on the potential safety issues related to the use of osmotically acting cathartics, especially disturbances of renal......Efficient cleansing of the colon before a colonoscopy or a radiological examination is essential. The osmotically acting cathartics (those given the Anatomical Therapeutic Chemical code A06AD) currently used for this purpose comprise products based on three main substances: sodium phosphate...... function and water and electrolyte balance. The available evidence indicates that PEG-ELS-based products are the safest option. Magnesium-citrate-based, hypertonic products should be administered with caution to elderly individuals and patients who are prone to develop disturbances in water and electrolyte...

  5. Effects of nociceptin/orphanin FQ on rats with cathartic colon

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To demonstrate the change and effect of nociceptin/orphanin FQ in the colon of rats with cathartic colon.METHODS: The cathartic colon model was established by feeding rats rhubarb for 3 mo, the changes of colonic electromyography were investigated by both suspension muscle strips test and serosal recordings of colonic myoelectrical activity. Immunohistochemical staining (S-P methods) and image analysis were used to determine the changes of nociceptin/orphanin FQ in the proximal colon and distal colon of rats with cathartic colon.RESULTS: Suspension muscle strips test in vitro showed OFQ (10-9-10-6 mol/L) concentration dependently caused an immediate tonic contraction in the isolated colon. But the increase of tension in cathartic colon was less than control groups (P<0.01). Intravenous administration of OFQ (1μg/kg) caused phasic contractions in the proximal colon, while the amplitude of phasic contractions caused by OFQ in cathartic colon was much lower than that in the control groups (2.58 ± 0.41 vs 4.16± 0.53, t= -2.6, P = 0.012). OFQ was highly expressed in the myenteric plexus of the rat colon but not in the muscle cells. The immunoreactivity of OFQ in the proximal colon in cathartic colon rats decreased significantly compared with the control group (P = 0.001).CONCLUSION: Colonic smooth muscle of cathartic colon showed low sensitivity to the stimulation of OFQ, suggesting that it might be caused by the abnormal distribution of OFQ or the abnormalities of receptors, leading to the disorganization of dynamic and incoordinated contractions.

  6. Changes of mu and kappa opioid receptors in cathartic colon of rat

    Institute of Scientific and Technical Information of China (English)

    LIU Bao-hua; MO Ping; JIA Hou-jun; LI Chun-xue; ZHANG Sheng-ben

    2004-01-01

    Objective: To oberve the changes of mu and kappa opioid receptors in the cathartic colon of rat, and to clarify that whether opioid receptors accounts for the occurrence of slow trait constipation (STC). Methods: The cathartiic colon model of rat was made by feeding with laxatives. The activity of mu and kappa opioid receptors in the cathartic colon of rat was measured by radio-ligand binding assay. Results: Compared with the control group, the maximal binding capacity (Bmax) and affinity(Kd) of mu opioid receptor in cathartic colon group were significantly increased (207. 00 ± 22. 90 fmol/mg·p vs 82. 00 ± 14.23 fmol/mg· p, P < 0.01 ;3.30 ± 0.45 mmol/L vs 2.40 ± 0.57 mmol/L, P < 0.05). The maximal binding capacity of kappa opioid receptor also showed a great increase (957. 00 ± 102. 41 fmol/mg· p vs 459.00 ± 52.41 fmol/mg·p, P < 0.01 ), but no significant difference of affinity was found between the two groups. Conclsion: The mu and kappa opioid receptors may be involved in the functional disorders of cathartic colon.

  7. In vivo genotoxic effects of dietary heme iron on rat colon mucosa and ex vivo effects on colon cells monitored by an optimized alkaline comet assay.

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    Océane, C Martin

    2015-04-01

    In conclusion, our results offer a suitable protocol to evaluate genotoxicity on in vivo cryopreserved colon mucosa and on in vitro murine colonic cells, with a middle throughput capacity. This protocol confirms the increase of genotoxicity in rat colon mucosa after an heme-iron diet. Moreover, this protocol enables the demonstration that aldehydes from heme-induced lipoperoxidation are responsible for this increase of genotoxicity.

  8. Sucrose, glucose and fructose have similar genotoxicity in the rat colon and affect the metabolism

    DEFF Research Database (Denmark)

    Hansen, Max; Baunsgaard, D.; Autrup, H.

    2008-01-01

    We have shown previously that a high sucrose intake increases the background level of somatic mutations and the level of bulky DNA adducts in the colon epithelium of rats. The mechanism may involve either glucose or fructose formed by hydrolysis of sucrose. Male Big Blue (R) rats were fed 30...... and proliferation were determined in colon, and a metabonomic analysis was performed in plasma and urine. The sugars increased the mutation rates in colon and the bulky adduct levels in colon and liver to a similar extent. All sugars decrease the caecal concentration of acetic acid and propionic acid....... The metabonomic studies indicated disturbed amino acid metabolism and decrease in plasma and urinary acetate as a common feature for all sugars and confirmed triglyceridemic effects of fructose. In conclusion, the genotoxicity may be related to the altered chemical environment in the caecum and thereby also...

  9. Effects of konjac glucomannan, inulin and cellulose on acute colonic responses to genotoxic azoxymethane.

    Science.gov (United States)

    Wu, Wen-Tzu; Yang, Lien-Chuan; Chen, Hsiao-Ling

    2014-07-15

    Mice were fed low-fibre, or that supplemented with soluble fibre (konjac glucomannan, KGM; inulin), or insoluble fibre (cellulose) to determine how these three fibres modulated the acute colonic responses to an azoxymethane (AOM) treatment. Results indicated that KGM and inulin exerted greater anti-genotoxic effects compared to cellulose and up-regulated the gene expressions of glutathione S-transferase and antioxidant enzymes. The apoptotic index in the distal colon was the greatest and the expression of Bcl-2 was the lowest in the KGM group 24h after the AOM treatment. On the other hand, the proliferative index and expression of Cyclin D1 were lower in all fibre groups. Furthermore, KGM increased cecal short-chain fatty acid contents, and both KGM and inulin increased fecal probiotic concentrations. This study suggested that soluble fibres were more effective than cellulose on ameliorating AOM-induced genotoxicity by up-regulating antioxidant enzyme genes, and enhancing epithelium apoptosis by down-regulating Bcl-2.

  10. 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.

  11. Flow cytometric evaluation of the contribution of ionic silver to genotoxic potential of nanosilver in human liver HepG2 and colon Caco2 cells.

    Science.gov (United States)

    Sahu, Saura C; Njoroge, Joyce; Bryce, Steven M; Zheng, Jiwen; Ihrie, John

    2016-04-01

    Exposure to nanosilver found in food- and cosmetics-related consumer products is of public concern because of the lack of information about its safety. In this study, two widely used in vitro cell culture models, human liver HepG2 and colon Caco2 cells, and the flow cytometric micronucleus (FCMN) assay were evaluated as tools for rapid predictive screening of the potential genotoxicity of nanosilver. Recently, we reported the genotoxicity of 20 nm nanosilver using these systems. In the current study presented here, we tested the hypothesis that the nanoparticle size and cell types were critical determinants of its genotoxicity. To test this hypothesis, we used the FCMN assay to evaluate the genotoxic potential of 50 nm nanosilver of the same shape, composition, surface charge and obtained from the same commercial source using the same experimental conditions and in vitro models (HepG2 and Caco2) as previously tested for the 20 nm silver. Results of our study show that up to the concentrations tested in these cultured cell test systems, the smaller (20 nm) nanoparticle is genotoxic to both the cell types by inducing micronucleus (MN). However, the larger (50 nm) nanosilver induces MN only in HepG2 cells, but not in Caco2 cells. Also in this study, we evaluated the contribution of ionic silver to the genotoxic potential of nanosilver using silver acetate as the representative ionic silver. The MN frequencies in HepG2 and Caco2 cells exposed to the ionic silver in the concentration range tested are not statistically significant from the control values except at the top concentrations for both the cell types. Therefore, our results indicate that the ionic silver may not contribute to the MN-forming ability of nanosilver in HepG2 and Caco2 cells. Also our results suggest that the HepG2 and Caco2 cell cultures and the FCMN assay are useful tools for rapid predictive screening of a genotoxic potential of food- and cosmetics-related chemicals including nanosilver.

  12. Dietary low-dose sucrose modulation of IQ-induced genotoxicity in the colon and liver of Big Blue((TM)) rats

    DEFF Research Database (Denmark)

    Moller, P.; Hansen, Max; Autrup, H.

    2003-01-01

    Earlier studies have indicated that sucrose increases 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced aberrant crypt foci in the colon. In this study, we investigated the role of sucrose in IQ-induced genotoxicity of the colon mucosa and liver. Big Blue(TM) rats were fed with IQ (20 ppm...... in feed) and/or sucrose (3.45 or 6.85 wt.% in feed) for 3 weeks. IQ increased DNA strand breaks in the colon, whereas the mutation frequency was increased in the liver. The level of IQ-induced DNA adducts was elevated in both colon mucosa cells and liver. In the liver, high sucrose intake increased...... the level of DNA adducts above that of IQ and low sucrose intake. Oxidative DNA damage detected in terms of 7-hydro-8-oxo-2'-deoxyguanosine by HPLC-EC, or endonuclease HI or formamidopyrimidine DNA glycosylase sensitive sites were unaltered in the colon and liver. Expression of ERCC1 and OGG1 mRNA levels...

  13. Experimental lead poisoning in Turkey Vultures, Cathartes aura

    Science.gov (United States)

    Carpenter, J.W.; Pattee, O.H.; Fritts, S.H.; Rattner, B.A.; Wiemeyer, Stanley N.; Royle, J. Andrew; Smith, M.R.

    2003-01-01

    Lead-induced mortality appears to have been a major factor in the decline of the California condor, Gymnogyps californianus. We orally dosed turkey vultures (Cathartes aura) with BB-sized lead shot from January 1988 through July 1988 to determine physiological response (delta-aminolevulinic acid dehydratase inhibition, erythrocyte protoporphyrin levels, anemia), diagnostic tissue lead concentrations (blood, liver, and kidney), and comparative sensitivity of this species. Two turkey vultures died and two became so intoxicated they were euthanized. Overall, responses of measured parameters were comparable to other species exposed to lead although there was considerable individual variation. Survival time (143-211 days), even with the large number of shot and constant redosing, was much longer than reported for other species of birds, suggesting considerable tolerance by turkey vultures to the deleterious effects of lead ingestion. Based on these observations, turkey vultures appear to be poor models for assessing the risk of lead poisoning to California condors or predicting their physiological response.

  14. Contribution of ionic silver to genotoxic potential of nanosilver in human liver HepG2 and colon Caco2 cells evaluated by the cytokinesis-block micronucleus assay.

    Science.gov (United States)

    Sahu, Saura C; Roy, Shambhu; Zheng, Jiwen; Ihrie, John

    2016-04-01

    Extensive human exposure to food- and cosmetics-related consumer products containing nanosilver is of public concern because of the lack of information about their safety. Genotoxicity is an important endpoint for the safety and health hazard assessment of regulated products including nanomaterials. The in vitro cytokinesis-block micronucleus (CBMN) assay is a very useful test for predictive genotoxicity testing. Recently, we have reported the genotoxicity of 20 nm nanosilver in human liver HepG2 and colon Caco2 cells evaluated using the CBMN assay. The objective of our present study was three-fold: (i) to evaluate if HepG2 and Caco2 cells are valuable in vitro models for rapid genotoxicity screening of nanosilver; (ii) to test the hypothesis that the nanoparticle size and cell types are critical determinants of its genotoxicity; and (iii) to determine if ionic silver contributes to the nanosilver genotoxicity. With these objectives in mind, we evaluated the genotoxic potential of 50 nm nanosilver of the same shape, composition, surface charge, obtained from the same commercial source, under the same experimental conditions and the same genotoxic CBMN endpoint used for the previously tested 20 nm silver. The ionic silver (silver acetate) was also evaluated under the same conditions. Results of our study show that up to the concentrations tested in these cell types, the smaller (20 nm) nanosilver induces micronucleus formation in both the cell types but the larger (50 nm) nanosilver and the ionic silver provide a much weaker response compared with controls under the same conditions.

  15. 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 coloni...

  16. Physico-chemical characteristics and cyto-genotoxic potential of ZnO and TiO2 nanoparticles on human colon carcinoma cells

    Science.gov (United States)

    Barone, F.; De Berardis, B.; Bizzarri, L.; Degan, P.; Andreoli, C.; Zijno, A.; De Angelis, I.

    2011-07-01

    The aim of the present study is to investigate the role of the physico-chemical properties of ZnO and TiO2 NPs in the potential cytotoxicity, genotoxicity and oxidative DNA damage induction on Caco-2 cell line. As negative control, fine TiO2 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 TiO2 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 TiO2 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.

  17. 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.

  18. Diagnostic performance of CT colonography with limited cathartic preparation in colorectal cancer screening; comparison with conventional colonoscopy

    Directory of Open Access Journals (Sweden)

    Mohammed Farghally Amin

    2015-09-01

    Conclusion: This study proved that CTC with limited cathartic bowel preparation and iodinated agents for fecal tagging can obtain high sensitivity and PPV values results for <5 mm polyps comparable to those obtained with conventional preparation with laxatives. Furthermore, this method could really improve the acceptance of CTC for colorectal cancer screening.

  19. Evaluation of the cytotoxicity and genotoxicity of extracts of mussels originating from Moroccan Atlantic coast, in human colonic epithelial cells Caco-2.

    Science.gov (United States)

    Nasser, Boubker; Moustaid, Khadija; Moukha, Serge; Mobio, Théophile A; Essamadi, Abdelkhalid; Creppy, Edmond E

    2008-08-01

    Industrial processing of phosphates generates chemical wastes which are, without any treatment, discharged directly into the Atlantic Ocean at Jorf Lasfar (JL), located 120 km south of Casablanca (Morocco) were shellfish are also collected by people without any control. Marine bivalves concentrate these pollutants by filtration and serve as vectors in human's exposure. The objective of this study was to test and compare in vitro on human intestinal cells (Caco-2) the cytotoxicity and genotoxicity of mussels (Mytilus galloprovincialis) extracts (either hydrophilic or lipophilic) collected at two coastal sites; JL (neighboring a phosphate processing plat-form) and Oualidia (OL) (a vegetable growing area) located 160 km south of Casablanca (i.e. 40 km south of JL). Using Caco-2 cells, the following end-points have been evaluated, cytotoxicity as measured by MTS test, inhibition of cellular macromolecules syntheses (DNA and protein) and genotoxicity evaluated by DNA fragmentation in agarose gel electrophoresis. The results indicated, that hydrophilic and lipophilic OL mussels extracts are cytotoxic and inhibit cellular macromolecules syntheses. Moreover these extracts damage the DNA in Caco-2 cells. The lipophilic JL mussels extract is cytotoxic, inhibits cellular macromolecules syntheses, and damages the DNA in Caco-2 cells whereas the hydrophilic extract of JL mussels fails to inhibit protein synthesis and does not damage the DNA. This extract rather enhances protein synthesis, suggesting possible metallothioneins induction by metal ions. Altogether these in vitro data indicate that mussels collected from OL could be more harmful than those from JL even though the later is closer to the pollution site than OL. Nevertheless consumption of mussels from all these areas may present a risk for humans. Epidemiological studies will be needed for global risk assessment in humans living in these areas especially those consuming see food regularly.

  20. Repeated use of an abandoned vehicle by nesting Turkey vultures (Cathartes aura)

    Science.gov (United States)

    Igl, L.D.; Peterson, S.L.

    2010-01-01

    Turkey Vultures (Cathartes aura) lay their eggs on an existing substrate in the dark recesses of a variety of natural sites (Kirk and Mossman 1998). Although an important requirement of Turkey Vulture nest-site selection is isolation from human disturbances (Kirk and Mossman 1998), their nests have been reported in abandoned buildings since at least the early 1800s (Nuttall 1832). Depopulation of rural areas in North America in recent decades has resulted in many abandoned buildings within the Turkey Vulture's breeding range (Peck 2003). Increased use of abandoned buildings by nesting Turkey Vultures has been implicated in the species' recent northward range expansion (Peck 2003, Nelson et al. 2005, Houston et al. 2007). Although abandoned or inoperative vehicles also are widespread in rural areas, we found no published literature documenting Turkey Vultures' use of these potential nest sites. Herein, we summarize the first documented incidence of a Turkey Vulture nesting in an abandoned vehicle.

  1. Fauna helmintológica peruana: Paryphostomum huaccaci sp. n. (Echinostomotidoe parásito de Cathartes aura jota Molino, 1782

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    Nicanor Ibáñez H.

    2014-06-01

    Full Text Available Es motivo de la presente nota, contribuir al conocimiento de un trematodo: Paryphostomum huaccaci sp. n. perteneciente o la Familia Echinostomatidae Poche, 1926 y que parásita a Cathartes aura jota Molina, 1782.

  2. Head color and caruncles of sympatric Cathartes vultures (Aves Cathartidae) in Guyana and their possible function in intra- and interspecific signaling

    DEFF Research Database (Denmark)

    Graves, Gary R.

    2016-01-01

    The naked heads of Cathartes vultures are widely believed to be adaptations for temperature regulation and to reduce plumage fouling during carrion feeding. Bright head color and the elaborate pattern of caruncles on the head and neck skin have a likely function in intra- and interspecific...

  3. Genotoxicity investigations on nanomaterials.

    Science.gov (United States)

    Oesch, Franz; Landsiedel, Robert

    2012-07-01

    This review is based on the lecture presented at the April 2010 nanomaterials safety assessment Postsatellite to the 2009 EUROTOX Meeting and summarizes genotoxicity investigations on nanomaterials published in the open scientific literature (up to 2008). Special attention is paid to the relationship between particle size and positive versus negative outcome, as well as the dependence of the outcome on the test used. Salient conclusions and outstanding recommendations emerging from the information summarized in this review are as follows: recognize that nanomaterials are not all the same; therefore know and document what nanomaterial has been tested and in what form; take nanomaterials specific properties into account; in order to make your results comparable with those of others and on other nanomaterials: use or at least include in your studies standardized methods; use in vivo studies to put in vitro results into perspective; take uptake and distribution of the nanomaterial into account; and in order to become able to make extrapolations to risk for human: learn about the mechanism of nanomaterials genotoxic effects. Past experience with standard non-nanosubstances already had shown that mechanisms of genotoxic effects can be complex and their elucidation can be demanding, while there often is an immediate need to assess the genotoxic hazard. Thus, a practical and pragmatic approach to genotoxicity investigations of novel nanomaterials is the use of a battery of standard genotoxicity testing methods covering a wide range of mechanisms. Application of these standard methods to nanomaterials demands, however, adaptations, and the interpretation of results from the genotoxicity testing of nanomaterials needs additional considerations exceeding those used for standard size materials.

  4. 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.

  5. 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.

  6. Genotoxic effect of alkaloids

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    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.

  7. Apparent tolerance of turkey vultures (Cathartes aura) to the non-steroidal anti-inflammatory drug diclofenac

    Science.gov (United States)

    Rattner, B.A.; Whitehead, M.A.; Gasper, G.; Meteyer, C.U.; Link, W.A.; Taggart, M.A.; Meharg, A.A.; Pattee, O.H.; Pain, D.J.

    2008-01-01

    The nonsteroidal anti-inflammatory drug diclofenac is extremely toxic to Old World Gyps vultures (median lethal dose 0.1?0.2 mg/kg), evoking visceral gout, renal necrosis, and mortality within a few days of exposure. Unintentional secondary poisoning of vultures that fed upon carcasses of diclofenac-treated livestock decimated populations in the Indian subcontinent. Because of the widespread use of diclofenac and other cyclooxygenase-2 inhibiting drugs, a toxicological study was undertaken in turkey vultures (Cathartes aura) as an initial step in examining sensitivity of New World scavenging birds. Two trials were conducted entailing oral gavage of diclofenac at doses ranging from 0.08 to 25 mg/kg body weight. Birds were observed for 7 d, blood samples were collected for plasma chemistry (predose and 12, 24, and 48 h and 7 d postdose), and select individuals were necropsied. Diclofenac failed to evoke overt signs of toxicity, visceral gout, renal necrosis, or elevate plasma uric acid at concentrations greater than 100 times the estimated median lethal dose reported for Gyps vultures. For turkey vultures receiving 8 or 25 mg/kg, the plasma half-life of diclofenac was estimated to be 6 h, and it was apparently cleared after several days as no residues were detectable in liver or kidney at necropsy. Differential sensitivity among avian species is a hallmark of cyclooxygenase-2 inhibitors, and despite the tolerance of turkey vultures to diclofenac, additional studies in related scavenging species seem warranted.

  8. 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...

  9. Genotoxicity of 2-alkylcyclobutanones, markers for an irradiation treatment in fat-containing food - Part I : cyto- and genotoxic potential of 2-tetradecylcyclobutanone

    NARCIS (Netherlands)

    Delincee, H; Soika, C; Horvatovich, P; Rechkemmer, G; Marchioni, E

    2002-01-01

    Previous experiments had indicated a slight genotoxic potential both in rat and in human colon cells of a sample of 2-dodecylcyclobutanone, a compound formed by irradiation of food containing palmitic acid in its triglycerides. Up to date, there is no evidence that 2-alkylcyclobutanones occur in non

  10. Colon cancer

    Science.gov (United States)

    Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma ... In the United States, colorectal cancer is one of the leading causes of deaths due to cancer. Early diagnosis can often lead to a complete cure. Almost ...

  11. The Food Contaminant Deoxynivalenol Exacerbates the Genotoxicity of Gut Microbiota

    Science.gov (United States)

    Payros, Delphine; Martin, Patricia; Secher, Thomas; Bracarense, Ana Paula F. L.; Boury, Michèle; Laffitte, Joelle; Pinton, Philippe; Oswald, Eric

    2017-01-01

    ABSTRACT An increasing number of human beings from developed countries are colonized by Escherichia coli strains producing colibactin, a genotoxin suspected to be associated with the development of colorectal cancers. Deoxynivalenol (DON) is the most prevalent mycotoxin that contaminates staple food—especially cereal products—in Europe and North America. This study investigates the effect of the food contaminant DON on the genotoxicity of the E. coli strains producing colibactin. In vitro, intestinal epithelial cells were coexposed to DON and E. coli producing colibactin. In vivo, newborn rats colonized at birth with E. coli producing colibactin were fed a DON-contaminated diet. Intestinal DNA damage was estimated by the phosphorylation of histone H2AX. DON exacerbates the genotoxicity of the E. coli producing colibactin in a time- and dose-dependent manner in vitro. Although DON had no effect on the composition of the gut microbiota, and especially on the number of E. coli, a significant increase in DNA damage was observed in intestinal epithelial cells of animals colonized by E. coli strains producing colibactin and coexposed to DON compared to animals colonized with E. coli strains unable to produce colibactin or animals exposed only to DON. In conclusion, our data demonstrate that the genotoxicity of E. coli strains producing colibactin, increasingly present in the microbiota of asymptomatic human beings, is modulated by the presence of DON in the diet. This raises questions about the synergism between food contaminants and gut microbiota with regard to intestinal carcinogenesis. PMID:28292979

  12. Genotoxic activity of praziquantel.

    Science.gov (United States)

    Montero, R; Ostrosky, P

    1997-12-01

    Praziquantel is a synthetic drug with a remarkable activity against parasites, particularly treamatodes and cestodes. Initial genotoxicity tests used a spectrum of endpoints including tests in bacteria, yeasts, mammalian cells and Drosophila and each one gave negative results. Effects on reproductive cells of mice were negative as well. However, host mediated studies in mice and humans were contradictory and a comutagenic effect with several mutagens and carcinogens was found. Later studies, including monitoring in humans and pigs have shown that Praziquantel induces a greater frequency of hyperploid lymphocytes as well as structural chromosomal aberrations, but not in all the individuals treated. In vitro studies have demonstrated that Praziquantel can induce micronuclei in syrian hamster embryonic (SHE) cells and in lymphocytes of some individuals. The same was found about structural chromosomal aberrations. Fetal death and fetal resorption were found when Praziquantel was administered in high doses to pregnant rats between the 6th and 10th day of gestation. Due to its efficiency as a parasiticide, Praziquantel is in use in Latin-American, Asiatic, African and East-European countries where infections by trematodes and cestodes are frequent. However, the extensive use of Praziquantel in multiple reinfections, in non-infected and non-diagnosed individuals for prevention, in higher doses or repeated doses for cysticercosis treatment and in individuals exposed to environmental mutagens, in conjunction with new findings about its metabolism and genotoxic properties, make it necessary to further evaluate the potential of this drug not only to be mutagenic per se, but to contribute in the development of neoplasm.

  13. 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

  14. 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.

  15. Genotoxicity of pyrrolizidine alkaloids.

    Science.gov (United States)

    Chen, Tao; Mei, Nan; Fu, Peter P

    2010-04-01

    Pyrrolizidine alkaloids (PAs) are common constituents of many plant species around the world. PA-containing plants are probably the most common poisonous plants affecting livestock and wildlife. They can inflict harm to humans through contaminated food sources, herbal medicines and dietary supplements. Half of the identified PAs are genotoxic and many of them are tumorigenic. The mutagenicity of PAs has been extensively studied in different biological systems. Upon metabolic activation, PAs produce DNA adducts, DNA cross-linking, DNA breaks, sister chromatid exchange, micronuclei, chromosomal aberrations, gene mutations and chromosome mutations in vivo and in vitro. PAs induced mutations in the cII gene of rat liver and in the p53 and K-ras genes of mouse liver tumors. It has been suggested that all PAs produce a set of (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine-derived DNA adducts and similar types of gene mutations. The signature types of mutations are G : C --> T : A transversion and tandem base substitutions. Overall, PAs are mutagenic in vivo and in vitro and their mutagenicity appears to be responsible for the carcinogenesis of PAs.

  16. Beryllium: genotoxicity and carcinogenicity.

    Science.gov (United States)

    Gordon, Terry; Bowser, Darlene

    2003-12-10

    Beryllium (Be) has physical-chemical properties, including low density and high tensile strength, which make it useful in the manufacture of products ranging from space shuttles to golf clubs. Despite its utility, a number of standard setting agencies have determined that beryllium is a carcinogen. Only a limited number of studies, however, have addressed the underlying mechanisms of the carcinogenicity and mutagenicity of beryllium. Importantly, mutation and chromosomal aberration assays have yielded somewhat contradictory results for beryllium compounds and whereas bacterial tests were largely negative, mammalian test systems showed evidence of beryllium-induced mutations, chromosomal aberrations, and cell transformation. Although inter-laboratory differences may play a role in the variability observed in genotoxicity assays, it is more likely that the different chemical forms of beryllium have a significant effect on mutagenicity and carcinogenicity. Because workers are predominantly exposed to airborne particles which are generated during the machining of beryllium metal, ceramics, or alloys, testing of the mechanisms of the mutagenic and carcinogenic activity of beryllium should be performed with relevant chemical forms of beryllium.

  17. Genotoxicity of clays with potential use in biopolymers for food packaging

    DEFF Research Database (Denmark)

    Sharma, Anoop Kumar; Mortensen, Alicja; Hadrup, Niels

    Genotoxicity of clays with potential use in biopolymers for food packaging Plastics produced from biopolymers are of commercial interest as they are manufactured from renewable resources such as agricultural crop wastes and have the potential to meet environmental and health requirements. Biopoly......®30B and Cloisite®Na+ by oral gavage and the comet assay will be performed on cells from different organs including the liver, colon and kidney. A fully automated comet assay scoring system (Imstar) will be used to evaluate the genotoxic potential....

  18. 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.

  19. 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.

  20. Fecal water genotoxicity is predictive of tumor-preventive activities by inulin-like oligofructoses, probiotics (Lactobacillus rhamnosus and Bifidobacterium lactis), and their synbiotic combination.

    Science.gov (United States)

    Klinder, Annett; Förster, Antje; Caderni, Giovanna; Femia, Angelo Pietro; Pool-Zobel, Beatrice L

    2004-01-01

    The measurement of fecal water genotoxicity in human colon cells could be a useful biomarker to study effects of diet in the colon. Here we assessed aqueous fecal extracts of samples from a chronic study with rats fed prebiotics, probiotics, and their combination. Treatments were maltodextrins (controls), inulin/oligofructoses (prebiotic), Lactobacillus rhamnosus, and Bifidobacterium lactis (probiotics) or both (synbiotic). Azoxymethane (AOM) was administered to initiate tumors. Rat feces were collected at 0 and 10 days and 2, 4, and 8 mo, and cecal contents were collected at 8 mo. Aqueous phases were prepared and tested for genotoxicity in HT29 colon cells using the comet assay. The studied types of intervention reduced fecal and cecal genotoxicity. DNA damage by samples from AOM-treated, tumor-free rats was significantly lower than from tumor-bearing animals, especially after 4 mo of synbiotic and prebiotic interventions. Inulin-based diets reduced exposure to genotoxins in the feces, directly reflecting the reported reduction of tumor incidence in these animals. Evidence is provided for the validity of this measurement as a biomarker of chemoprevention because 1) fecal water genotoxicity reflected genotoxic exposure in the cecum, 2) tumor incidence and fecal genotoxicity were directly related, and 3) these interventions reduced tumor risks by reducing exposure to genotoxins in the gut.

  1. Colonic locomotion

    NARCIS (Netherlands)

    Dodou, D.

    2006-01-01

    The most effective screening method for colonic cancer is colonoscopy. However, colonoscopy cannot be easily embraced by the population because of the related pain intensity. Robotic devices that pull themselves forward through the colon are a possible alternative. The main challenge for such device

  2. Colonic angiodysplasia

    Energy Technology Data Exchange (ETDEWEB)

    Vallee, C.; Legmann, P.; Garnier, T.; Levesque, M.; Favriel, J.M.

    1984-11-01

    The main clinical, endoscopic and radiographic findings in thirty documented cases of colonic angiodysplasia or vacular ectasia are described. We emphasise the association with colonic diverticulosis and cardiovascular pathology, describe the histological changes, summarize the present physiopathological hypothesis, and consider the various therapeutic approaches.

  3. Overview of genotoxic impurities in pharmaceutical development.

    Science.gov (United States)

    Bercu, Joel P; Dobo, Krista L; Gocke, Elmar; McGovern, Timothy J

    2009-01-01

    This symposium focuses on the management of genotoxic impurities in the synthesis of pharmaceuticals. Recent developments in both Europe and United States require sponsors of new drug applications to develop processes to control the risks of potential genotoxic impurities. Genotoxic impurities represent a special case relative to the International Conference on Harmonisation Q3A/Q3B guidances, because genotoxicity tests used to qualify the drug substance may not be sufficient to demonstrate safety of a potentially genotoxic impurity. The default risk management approach for a genotoxic impurity is the threshold of toxicological concern unless a more specific risk characterization is appropriate. The symposium includes descriptions of industry examples where impurities are introduced and managed in the synthesis of a pharmaceutical. It includes recent regulatory developments such as the "staged threshold of toxicological concern" when administration is of short duration (eg, during clinical trials).

  4. Lead- induced genotoxicity in wheat

    Directory of Open Access Journals (Sweden)

    Elena Truta

    2010-02-01

    Full Text Available The changes induced in cytogenetic parameters from root meristems of Triticum aestivum cv. Maruca seedlings have been studied after treatment with lead acetate and lead nitrate solutions, at four concentrations (10, 25, 50, 100 μM containing 2.07, 5.18, 10.36, respectively 20.72 μg ml-1 Pb2+. Lead induced mitosis disturbances in root meristematic cells of wheat seedlings, expressed mainly in decrease of mitotic index and changes in preponderance of division phases. This heavy metal has genotoxic effects, expressed in the occurrence of many chromosomal aberrations in all Pb2+ treated variants. Pb2+ nitrate shows a more pronounced genotoxic potential than lead acetate trihydrate.

  5. 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

  6. Evolution of genotoxicity test methods in Japan.

    Science.gov (United States)

    Sofuni, Toshio

    2017-01-01

    The evolution of methods to assess genotoxicity of test compounds is thought to be one of the important subjects in The Japanese Environmental and Mutagen Society (JEMS). In 1970, the Ministry of Education of Japan (at that time) organized a research group (Organizer: Y. Tazima, National Institute of Genetics), and started a systematic research on the genotoxic effects induced by chemical substances. Considering the importance of this issue through the outcomes of the research group, JEMS was established in 1972, and President Tazima organized the 1st annual meeting in the August in Tokyo with the participation of experts in this field working in national institutes, universities and others in Japan. The discovery that food additives possessed genotoxic potential triggered various scientific activities in the field of genotoxicity. Another important point was the correlation between genotoxicity and carcinogenicity, in which the establishment of the reverse mutation assay played an important role. Other critical factors, such as side effects of drugs, occupational cancer, and environmental pollution due to genotoxic chemicals, emphasized the importance of genotoxicity tests for human safety. The tests performed to assess genotoxicity from 1960s to 1980s will be described to understand that many different genotoxic methodologies were discussed in these periods.

  7. 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.

  8. Colonic Lipomas Mimicking Colon Cancer

    Directory of Open Access Journals (Sweden)

    Berna AYTAÇ

    2010-09-01

    Full Text Available Objective: Colonic lipomas are uncommon tumors of the gastrointestinal tract. Most of these tumors are asymptomatic and usually detected incidentally during colonoscopy or laparotomy and do not require treatment. Large lipomas are usually symptomatic and may mimic clinic manifestations of colonic carcinoma. Here we studied seven cases of submucosal and intramuscular colonic lipomas to evaluate the clinical features, diagnosis and treatment of this disease.Material and Method: Seven patients who were diagnosed with colonic lipoma between 1999 and 2006 were evaluated as regards age, gender, size of tumor, anatomic site, symptoms, location and treatment modality.Result: The mean age was 57.8± 14.7 years. Five patients were male and two were female. The size of the lipomas ranged from 1 to 5.5 cm and all were symptomatic except one patient. Five of the gastrointestinal lipomas were located submucosally and 2 intramurally. Five lipomas arose from the ascending colon, 1 from the hepatic flexure and 1 from the splenic flexure. Four large GI lipomas were removed by subtotal resection and one case underwent hemicolectomy while two pedunculated lipomas were resected by polypectomy. No recurrence was found after at least one year follow-up with endoscopic examination.Conclusion: Colonic lipomas may mimic malignancy with their clinical manifestations. Appropriate radiological and colonoscopic evaluation is essential to avoid unnecessary wide resections.

  9. Colon Cancer

    Centers for Disease Control (CDC) Podcasts

    2013-11-05

    In this podcast, Dr. Tom Frieden, CDC Director, discusses colon cancer and the importance of early detection.  Created: 11/5/2013 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 3/6/2014.

  10. Colon Polyps

    Science.gov (United States)

    ... whole grains. Reduce your fat intake. Limit alcohol consumption. Don't use tobacco. Stay physically active and maintain a healthy body weight. Talk to your doctor about calcium. Studies have shown that increasing your consumption of calcium may help prevent recurrence of colon ...

  11. Learning about Colon Cancer

    Science.gov (United States)

    ... What do we know about heredity and colon cancer? Colon cancer, a malignant tumor of the large intestine, ... page Additional Resources for Information on Hereditary Colon Cancer Colon and Rectal Cancer Information [cancer.gov] The most ...

  12. Genotoxicity studies on green tea catechin.

    Science.gov (United States)

    Ogura, R; Ikeda, N; Yuki, K; Morita, O; Saigo, K; Blackstock, C; Nishiyama, N; Kasamatsu, T

    2008-06-01

    The beneficial effects of tea catechins are well documented. We evaluated the genotoxic potential of a green tea catechin preparation using established genotoxicity assays, including a bacterial reverse mutation assay (Ames test), a chromosomal aberration assay in cultured Chinese hamster lung cells (CHL/IU), a mouse lymphoma L5178Y/tk assay, and a bone marrow micronucleus (MN) assay in ICR CD mice and SD rats. No significant increases in the number of revertant colonies were observed in the Ames test, but positive responses were observed in two in vitro assays: the chromosomal aberration assay and mouse lymphoma L5178/tk assay. However, the in vivo study demonstrated no significant increase in micronucleated polychromatic erythrocytes (MNPCE) in the bone marrow of both ICR CD mice and SD rats administered a high dose of the green tea catechin preparation up to 2000mg/kg. Combined with favorable epidemiological information suggesting a chemopreventive effect of tea catechins on carcinogenesis, we conclude that green tea catechin presents no significant genotoxic concern under the anticipated conditions of use. These results are consistent with other genotoxicity studies of tea catechins, which show minimal, if any, genotoxic potential.

  13. 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.

  14. Cobalt and antimony: genotoxicity and carcinogenicity.

    Science.gov (United States)

    De Boeck, Marlies; Kirsch-Volders, Micheline; Lison, Dominique

    2003-12-10

    The purpose of this review is to summarise the data concerning genotoxicity and carcinogenicity of Co and Sb. Both metals have multiple industrial and/or therapeutical applications, depending on the considered species. Cobalt is used for the production of alloys and hard metal (cemented carbide), diamond polishing, drying agents, pigments and catalysts. Occupational exposure to cobalt may result in adverse health effects in different organs or tissues. Antimony trioxide is primarily used as a flame retardant in rubber, plastics, pigments, adhesives, textiles, and paper. Antimony potassium tartrate has been used worldwide as an anti-shistosomal drug. Pentavalent antimony compounds have been used for the treatment of leishmaniasis. Co(II) ions are genotoxic in vitro and in vivo, and carcinogenic in rodents. Co metal is genotoxic in vitro. Hard metal dust, of which occupational exposure is linked to an increased lung cancer risk, is proven to be genotoxic in vitro and in vivo. Possibly, production of active oxygen species and/or DNA repair inhibition are mechanisms involved. Given the recently provided proof for in vitro and in vivo genotoxic potential of hard metal dust, the mechanistic evidence of elevated production of active oxygen species and the epidemiological data on increased cancer risk, it may be advisable to consider the possibility of a new evaluation by IARC. Both trivalent and pentavalent antimony compounds are generally negative in non-mammalian genotoxicity tests, while mammalian test systems usually give positive results for Sb(III) and negative results for Sb(V) compounds. Assessment of the in vivo potential of Sb2O3 to induce chromosome aberrations (CA) gave conflicting results. Animal carcinogenicity data were concluded sufficient for Sb2O3 by IARC. Human carcinogenicity data is difficult to evaluate given the frequent co-exposure to arsenic. Possible mechanisms of action, including potential to produce active oxygen species and to interfere with

  15. 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.

  16. Cation Exchange Resins and colonic perforation. What surgeons need to know

    Science.gov (United States)

    Rodríguez-Luna, María Rita; Fernández-Rivera, Enrique; Guarneros-Zárate, Joaquín E.; Tueme-Izaguirre, Jorge; Hernández-Méndez, José Roberto

    2015-01-01

    Introduction Since 1961 the use of Cation Exchange Resins has been the mainstream treatment for chronic hyperkalemia. For the past 25 years different kind of complications derived from its clinical use have been recognized, being the colonic necrosis the most feared and lethal of all. Presentation of case We report a case of a 72-year-old patient with chronic kidney disease, treated with calcium polystyrene sulfonate for hyperkalemia treatment who presented in the emergency department with constipation treated with hypertonic cathartics. With clinical deterioration 48 h later progressed with colonic necrosis requiring urgent laparotomy, sigmoidectomy and open abdomen management with subsequent rectal stump perforation and dead. The histopathology finding: calcium polystyrene sulfonate embedded in the mucosa, consistent with the cause of perforation. Discussion Lillemoe reported the first case series of five uremic patients with colonic perforation associated with the use of SPS in sorbitol in 1987 and in 2009 the FDA removed from the market the SPS containing 70% of sorbitol. The pathophysiologic change of CER goes from mucosal edema, ulcers, pseudomembranes, and the most severe case transmural necrosis. Up to present day, some authors have questioned the use of CER in the setting of lowering serum potassium. Despite its worldwide use in hyperkalemia settings, multiple studies have not demonstrated a significant potassium excretion by CER. Conclusion Despite the low incidence of colonic complication and lethal colonic necrosis associated with the CER clinical use, the general surgeon needs a high index of suspicion when dealing with patients treated with CER and abdominal pain. PMID:26439420

  17. "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.

  18. International current of the genotoxicity testing

    Institute of Scientific and Technical Information of China (English)

    HayaM

    2002-01-01

    One of the goals of the genetic toxicology is to assess the risk to humans that derives from genotoxic agents.The risk involves both somatic and germ cells,with damage to the former resulting in cancer and damage to the latter in adverse effects that could be transmitted through generations.It is necessary to consider not only direct effects,but also effects that are the result of analtered environment.To perform an accurate risk assessment.it is necessary to evaluate genotoxic hazards in ways that are appropriate both methodologically and strategically.In establishing a genotoxicity assay system,international cooperation is important because it enables us to incorporate the thoughts of specialists everywhere and to learn of specific regional concerns.Here I will introduce the “Guidance on a Strategy for Testing of Chemicals for Mutagenicity” recently reported by the UK Committee on Mutagenicity (COM) and also I will briefly summarize the activities of the International Workshop on Genotoxicity Test Procedures(IWGTP).The first and the second workshops focused on methodology.we started to include the strategic issues as well as procedures in the third workshop.Starting with the 3rd IWGT,the workshop will become an activity of the International Association of EMSs.

  19. Genotoxicity assessment of 4-methylimidazole: regulatory perspectives.

    Science.gov (United States)

    Morita, Takeshi; Uneyama, Chikako

    2016-01-01

    4-Methylimidazole (4-MI) is formed as a result of the Maillard reaction process, and therefore is found in many foods and beverages. It is also found in soft drinks (i.e., cola) as a by-product in the production of some caramel colors. NTP bioassays revealed clear evidence of lung carcinogenicity of 4-MI in male and female mice, but not in rats and then IARC classified 4-MI as group 2B carcinogen. Genotoxicity studies with 4-MI were negative in the Ames tests and in the erythrocyte micronucleus tests with mice or rats. US California EPA (CEPA) evaluated the testing has not been adequately comprehensive to rule out a genotoxic mode of action; as target tissue of the carcinogenicity of 4-MI was lung, the lung should be used as a source tissue for in vitro metabolic activation system. Thus, CEPA defined the No Significant Risk Level (NSRL) for 10(-5) lifetime risk level of cancer by 4-MI as 29 μg/day based on the non-threshold approach. As higher levels of 4-MI than the NSRL were identified in some kinds of cola, health concerns of 4-MI were drawn the attention. On the other hand, other regulatory bodies (e.g., European Food Safety Authority, EFSA) showed no concerns of 4-MI from the use of caramel colors in food. EFSA evaluated 4-MI is not genotoxic, so, non-observed adverse effect level of 4-MI was considered to be 80 mg/kg/day. In this paper, genotoxic assessments of 4-MI in different regulatory bodies are presented and the risk evaluation of 4-MI is discussed based on new genotoxicity data.

  20. 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

  1. 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.

  2. 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.

  3. Cytotoxicity and genotoxicity of butyl cyclohexyl phthalate.

    Science.gov (United States)

    Köksal, Çinel; Nalbantsoy, Ayse; Karabay Yavaşoğlu, N Ülkü

    2016-03-01

    Butyl cyclohexyl phthalate (BCP) is frequently used in personal care products, medical and household applications. The aim of this study is therefore to evaluate possible cytotoxicity and genotoxicity of BCP using in vitro and in vivo assays. The in vitro cytotoxic effect of BCP was investigated on mouse fibroblastic cell line (L929 cells) by MTT assay. The result showed that BCP inhibits cell proliferation in a concentration-dependent manner (IC50 value = 0.29 µg/mL). For genotoxicity assessment, tested concentrations of BCP demonstrated mutagenic activity in the presence of S9 mix with the Salmonella strain TA100 in the Ames test. Results showed that BCP is a secondary mutagenic substance even in low concentrations. The data obtained from 28-days repeated toxicity tests on mice revealed that BCP caused abnormalities of chromosome number, in a dose-dependent manner. Additionally, DNA damage, particularly DNA strand breaks, was assessed by Comet assay. The test result shows that BCP seemed to have genotoxic potential at a high level of exposure.

  4. Genotoxic activity of a technical toxaphene mixture and its photodegradation products in SOS genotoxicity tests.

    Science.gov (United States)

    Bartos, Tomás; Skarek, Michal; Cupr, Pavel; Kosubová, Petra; Holoubek, Ivan

    2005-01-03

    Toxaphene (CAS No. 800-35-2) is a complex mixture of several hundred components that was used worldwide primarily as an agricultural pesticide with insecticide effects in the second half of the 20th century. In vitro investigations of the genotoxicity and mutagenicity of toxaphene were generally described in the literature, but they provided somewhat equivocal results. We re-evaluated the genotoxicity of technical toxaphene in two prokaryotic systems. The SOS Chromotest showed high sensitivity to toxaphene: three concentrations (40, 20 and 10 mg/l) were clearly positive and the dose-response effect was evident. In the umuC assay, a dose-dependent increase in genotoxic activity was observed at toxaphene concentrations from 2.5 to 40.0 mg/l, but these results were found to be not significant. The genotoxicity of toxaphene and its photodegradation products after UV-irradiation (3-6-9 h) at concentrations ranging from 7.5 to 60.0 mg/l was also examined in this study. An irradiated solution of technical toxaphene after 3 h showed no significant evidence of bacterial growth inhibition. However, exposure of Salmonella to 6 h UV-irradiated toxaphene showed a toxic effect compared with the negative control. After 9 h irradiation, a decrease of bacterial growth was observed. Activity of beta-galactosidase in the presence of a toxaphene solution was significantly increased after 6 and 9 h irradiation, reaching values that were 2.4- and 3.1-fold higher, respectively, than the control, which exceeded the criteria of significant genotoxicity. These results show that while technical toxaphene is a weak, direct-acting mutagen in some bacterial tests, a dose-dependent toxicity and genotoxicity of its photoproducts could be conclusively demonstrated by the umuC test.

  5. A predictive toxicogenomics signature to classify genotoxic versus non-genotoxic chemicals in human TK6 cells

    Directory of Open Access Journals (Sweden)

    Andrew Williams

    2015-12-01

    Full Text Available Genotoxicity testing is a critical component of chemical assessment. The use of integrated approaches in genetic toxicology, including the incorporation of gene expression data to determine the DNA damage response pathways involved in response, is becoming more common. In companion papers previously published in Environmental and Molecular Mutagenesis, Li et al. (2015 [6] developed a dose optimization protocol that was based on evaluating expression changes in several well-characterized stress-response genes using quantitative real-time PCR in human lymphoblastoid TK6 cells in culture. This optimization approach was applied to the analysis of TK6 cells exposed to one of 14 genotoxic or 14 non-genotoxic agents, with sampling 4 h post-exposure. Microarray-based transcriptomic analyses were then used to develop a classifier for genotoxicity using the nearest shrunken centroids method. A panel of 65 genes was identified that could accurately classify toxicants as genotoxic or non-genotoxic. In Buick et al. (2015 [1], the utility of the biomarker for chemicals that require metabolic activation was evaluated. In this study, TK6 cells were exposed to increasing doses of four chemicals (two genotoxic that require metabolic activation and two non-genotoxic chemicals in the presence of rat liver S9 to demonstrate that S9 does not impair the ability to classify genotoxicity using this genomic biomarker in TK6cells.

  6. Sucrose and IQ induced mutations in rat colon by independent

    DEFF Research Database (Denmark)

    Hansen, Max; Hald, M. T.; Autrup, H.

    2004-01-01

    Sucrose-rich diets have repeatedly been observed to have co-carcinogenic actions in colon and liver of rats and to increase the number of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) induced aberrant crypt foci in rat colon. To investigate a possible interaction between sucrose and IQ...... on the genotoxicity in rat liver and colon, we gave Big Blue rats(TM) a diet containing sucrose (0%, 3.45% or 13.4% w/w) and/or IQ (70 ppm) for a period of 3 weeks. Sucrose and IQ increased the mutation frequency in the colon. The effect of combined treatments with IQ and sucrose on the mutation frequencies...... was additive indicating that sucrose and IQ act independently. This was supported by the mutation spectra where sucrose expands the background mutations in the colon, whereas IQ, in other studies, more specifically has induced G:C --> T:A transversions. In the liver IQ increased the mutation frequency, whereas...

  7. Genotoxicity evaluation of alpha-linolenic acid-diacylglycerol oil

    Directory of Open Access Journals (Sweden)

    Hiroshi Honda

    2016-01-01

    Full Text Available The alpha-linolenic acid (ALA-diacylglycerol (DAG oil is an edible oil enriched with DAG (>80% and ALA (>50%. Although DAG oil, which mainly consists of oleic and linoleic acids has no genotoxic concerns, the fatty acid composition could affect the chemical property of DAG. Therefore, the purpose of this study was to evaluate the genotoxicity of ALA-DAG oil using standard genotoxicity tests in accordance with the OECD guidelines. ALA-DAG oil showed negative results in the bacterial reverse mutation test (Ames test and in vitro micronucleus test in cultured Chinese hamster lung cells with and without metabolic activation, and in the in vivo bone marrow micronucleus test in mice. Our results did not show any genotoxicity, suggesting that the fatty acid composition had no deleterious effects. We conclude that ALA-DAG oil had no genotoxicity concerns under the testing conditions.

  8. Genotoxicity of Anesthetics Evaluated In Vivo (Animals)

    Science.gov (United States)

    Braz, Mariana G.; Karahalil, Bensu

    2015-01-01

    The anesthesia has been improved all over the years. However, it can have impact on health, in both patients and animals anesthetized, as well as professionals exposed to inhaled anesthetics. There is continuing effort to understand the possible effects of anesthetics at molecular levels. Knowing the effects of anesthetic agents on genetic material could be a valuable basic support to better understand the possible mechanisms of these agents. Thus, the purpose of this review is to provide an overview on the genotoxic potential, evaluated in animal models, of many anesthetics that have already been used and those currently used in anesthesia. PMID:26199936

  9. 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

  10. Genotoxicity assessment of 4-methylimidazole: regulatory perspectives

    OpenAIRE

    Morita, Takeshi; Uneyama, Chikako

    2016-01-01

    4-Methylimidazole (4-MI) is formed as a result of the Maillard reaction process, and therefore is found in many foods and beverages. It is also found in soft drinks (i.e., cola) as a by-product in the production of some caramel colors. NTP bioassays revealed clear evidence of lung carcinogenicity of 4-MI in male and female mice, but not in rats and then IARC classified 4-MI as group 2B carcinogen. Genotoxicity studies with 4-MI were negative in the Ames tests and in the erythrocyte micronucle...

  11. Genotoxicity Expert Panel review: weight of evidence evaluation of the genotoxicity of glyphosate, glyphosate-based formulations, and aminomethylphosphonic acid.

    Science.gov (United States)

    Brusick, David; Aardema, Marilyn; Kier, Larry; Kirkland, David; Williams, Gary

    2016-09-01

    In 2015, the International Agency for Research on Cancer (IARC) published a monograph concluding there was strong evidence for genotoxicity of glyphosate and glyphosate formulations and moderate evidence for genotoxicity of the metabolite aminomethylphosphonic acid (AMPA). These conclusions contradicted earlier extensive reviews supporting the lack of genotoxicity of glyphosate and glyphosate formulations. The IARC Monograph concluded there was strong evidence of induction of oxidative stress by glyphosate, glyphosate formulations, and AMPA. The Expert Panel reviewed the genotoxicity and oxidative stress data considered in the IARC Monograph, together with other available data not considered by IARC. The Expert Panel defined and used a weight of evidence (WoE) approach that included ranking of studies and endpoints by the strength of their linkage to events associated with carcinogenic mechanisms. Importantly, the Expert Panel concluded that there was sufficient information available from a very large number of regulatory genotoxicity studies that should have been considered by IARC. The WoE approach, the inclusion of all relevant regulatory studies, and some differences in interpretation of individual studies led to significantly different conclusions by the Expert Panel compared with the IARC Monograph. The Expert Panel concluded that glyphosate, glyphosate formulations, and AMPA do not pose a genotoxic hazard and the data do not support the IARC Monograph genotoxicity evaluation. With respect to carcinogenicity classification and mechanism, the Expert Panel concluded that evidence relating to an oxidative stress mechanism of carcinogenicity was largely unconvincing and that the data profiles were not consistent with the characteristics of genotoxic carcinogens.

  12. 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....

  13. Forskolin: genotoxicity assessment in Allium cepa.

    Science.gov (United States)

    Mohammed, Khalid Pasha; Aarey, Archana; Tamkeen, Shayesta; Jahan, Parveen

    2015-01-01

    Forskolin, a diterpene, 7β-acetoxy-8,13-epoxy-1α,6β,9α-trihydroxy-labd-14-en-11-one (C22H34O7) isolated from Coleus forskohlii, exerts multiple physiological effects by stimulating the enzyme adenylate cyclase and increasing cyclic adenosine monophosphate (cAMP) concentrations. Forskolin is used in the treatment of hypertension, congestive heart failure, eczema, and other diseases. A cytogenetic assay was performed in Allium cepa to assess possible genotoxic effects of forskolin. Forskolin was tested at concentrations 5-100 μM for exposure periods of 24 or 48 h. Treated samples showed significant reductions in mitotic index (p < 0.05) and increases in the frequency of chromosome aberrations (p < 0.01) at both exposure times. The treated meristems showed chromosome aberrations including sticky metaphases, sticky anaphases, laggard, anaphase bridges, micronuclei, polyploidy, fragments, breaks, and C-mitosis. Forskolin may cause genotoxic effects and further toxicological evaluations should be conducted to ensure its safety.

  14. Genotoxicity evaluation of sesamin and episesamin.

    Science.gov (United States)

    Hori, Hisako; Takayanagi, Tomomi; Kamada, Yoko; Shimoyoshi, Satomi; Ono, Yoshiko; Kitagawa, Yoshinori; Shibata, Hiroshi; Nagao, Minako; Fujii, Wataru; Sakakibara, Yutaka

    2011-02-03

    Sesamin is a major lignan that is present in sesame seeds and oil. Sesamin is partially converted to its stereoisomer, episesamin, during the refining process of non-roasted sesame seed oil. We evaluated the genotoxicity of these substances through the following tests: a bacterial reverse mutation assay (Ames test), a chromosomal aberration test in cultured Chinese hamster lung cells (CHL/IU), a bone marrow micronucleus (MN) test in Crlj:CD1 (ICR) mice, and a comet assay using the liver of Sprague-Dawley (SD) rats. Episesamin showed negative results in the Ames test with and without S9 mix, in the in vitro chromosomal aberration test with and without S9 mix, and in the in vivo comet assay. Sesamin showed negative results in the Ames test with and without S9 mix. In the in vitro chromosomal aberration test, sesamin did not induce chromosomal aberrations in the absence of S9 mix, but induced structural abnormalities at cytotoxic concentrations in the presence of S9 mix. Oral administration of sesamin at doses up to 2.0g/kg did not cause a significant increase in either the percentage of micronucleated polychromatic erythrocytes in the in vivo bone marrow MN test or in the % DNA in the comet tails in the in vivo comet assay of liver cells. These findings indicate that sesamin does not damage DNA in vivo and that sesamin and episesamin have no genotoxic activity.

  15. 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.

  16. 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.

  17. Colon cancer screening

    Science.gov (United States)

    Screening for colon cancer; Colonoscopy - screening; Sigmoidoscopy - screening; Virtual colonoscopy - screening; Fecal immunochemical test; Stool DNA test; sDNA test; Colorectal cancer - screening; Rectal ...

  18. Colon capsule endoscopy

    Institute of Scientific and Technical Information of China (English)

    Ignacio Fernandez-Urien; Cristina Carretero; Ana Borda; Miguel Mu(n)oz-Navas

    2008-01-01

    Wireless capsule endoscopy has become the first imaging tool for small bowel examination.Recently,new capsule endoscopy applications have been developed,such as esophageal capsule endoscopy and colon capsule endoscopy.Clinical trials results have shown that colon capsule endoscopy is feasible,accurate and safe in patients suffering from colonic diseases.It could be a good alternative in patients refusing conventional colonoscopy or when it is contraindicated.Upcoming studies are needed to demonstrate its utilty for colon cancer screening and other indications such us ulcerative colitis.Comparative studies including both conventional and virtual colonoscopy are also required.

  19. Steviol glycoside safety: is the genotoxicity database sufficient?

    Science.gov (United States)

    Urban, J D; Carakostas, M C; Brusick, D J

    2013-01-01

    The safety of steviol glycoside sweeteners has been extensively reviewed in the literature. National and international food safety agencies and approximately 20 expert panels have concluded that steviol glycosides, including the widely used sweeteners stevioside and rebaudioside A, are not genotoxic. However, concern has been expressed in recent publications that steviol glycosides may be mutagenic based on select studies representing a small fraction of the overall database, and it has been suggested that further in vivo genotoxicity studies are required to complete their safety profiles. To address the utility of conducting additional in vivo genotoxicity studies, this review evaluates the specific genotoxicity studies that are the sources of concern, and evaluates the adequacy of the database including more recent genotoxicity data not mentioned in those publications. The current database of in vitro and in vivo studies for steviol glycosides is robust and does not indicate that either stevioside or rebaudioside A are genotoxic. This, combined with a lack of evidence for neoplasm development in rat bioassays, establish the safety of all steviol glycosides with respect to their genotoxic/carcinogenic potential.

  20. 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.

  1. LEAKAGE OF COLONIC ANASTOMOSIS AFTER COLON RESECTION

    Institute of Scientific and Technical Information of China (English)

    Kanellos I; Pramateftakis MG

    2004-01-01

    Objective To present the diagnosis and management of anastomotic leakage after colon resection. Methods Early diagnosis and urgent therapeutic intervention are required in order to avert life-threatening conditions that may be caused by anastomotic leakage. Results The diagnosis of anastomotic leakage is based on clinical features, peripheral blood investigations and abdominal computed tomography (CT) scan. Major leaks are defined by symptoms of peritonitis and septicaemia due to leakage. Major leaks should be managed operatively. Minor leaks can be managed conservatively with successful outcomes. Conclusion Leakage of colonic anastomosis remains the most serious complication after colon resection. It is a major cause of postoperative morbidity and mortality. A high index of suspicion is required in order to detect early, nonspecific signs of a leakage and urgent surgical intervention is usually required to avert life-threatening events.

  2. CT findings of colonic complications associated with colon cancer.

    Science.gov (United States)

    Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Young Tong; Kim, Chang-Jin

    2010-01-01

    A broad spectrum of colonic complications can occur in patients with colon cancer. Clinically, some of these complications can obscure the presence of underlying malignancies in the colon and these complications may require emergency surgical management. The complications of the colon that can be associated with colon cancer include obstruction, perforation, abscess formation, acute appendicitis, ischemic colitis and intussusception. Although the majority of these complications only rarely occur, familiarity with the various manifestations of colon cancer complications will facilitate making an accurate diagnosis and administering prompt management in these situations. The purpose of this pictorial essay is to review the CT appearance of the colonic complications associated with colon cancer.

  3. CT Findings of Colonic Complications Associated with Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Young Tong; Kim, Chang Jin [Cheonan Hospital, Soonchunhyang University, Cheonan (Korea, Republic of)

    2010-04-15

    A broad spectrum of colonic complications can occur in patients with colon cancer. Clinically, some of these complications can obscure the presence of underlying malignancies in the colon and these complications may require emergency surgical management. The complications of the colon that can be associated with colon cancer include obstruction, perforation, abscess formation, acute appendicitis, ischemic colitis and intussusception. Although the majority of these complications only rarely occur, familiarity with the various manifestations of colon cancer complications will facilitate making an accurate diagnosis and administering prompt management in these situations. The purpose of this pictorial essay is to review the CT appearance of the colonic complications associated with colon cancer.

  4. Colon cancer - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100157.htm Colon cancer - Series—Normal anatomy To use the sharing features on this page, please enable JavaScript. Go to slide 1 out of 5 Go to slide 2 out of ... to slide 5 out of 5 Overview The colon, or large intestine, is a muscular tube that ...

  5. Cat scratch colon.

    Science.gov (United States)

    Ruiz-Rebollo, M Lourdes; Velayos-Jiménez, Benito; Prieto de Paula, José María; Alvarez Quiñones, María; González Hernández, José Manuel

    2011-01-01

    Over the past few years, we have read several publications regarding the term "cat scratch colon." This neologism was developed to define some bright red linear markings seen in the colonic mucosa that resemble scratches made by a cat. We would like to communicate a recent case attended at our institution.

  6. Cat Scratch Colon

    Directory of Open Access Journals (Sweden)

    M. Lourdes Ruiz-Rebollo

    2011-01-01

    Full Text Available Over the past few years, we have read several publications regarding the term “cat scratch colon.” This neologism was developed to define some bright red linear markings seen in the colonic mucosa that resemble scratches made by a cat. We would like to communicate a recent case attended at our institution.

  7. Evaluation of the genotoxicity of cellulose nanofibers

    Directory of Open Access Journals (Sweden)

    de Lima R

    2012-07-01

    plant cells, the most genotoxic nanofibers were those derived from green, white, and brown cotton, and curaua, while genotoxicity in animal cells was observed using nanofibers from brown cotton and curaua. An important finding was that ruby cotton nanofibers did not cause any significant DNA breaks in the cell types employed.Conclusion: This work demonstrates the feasibility of determining the genotoxic potential of nanofibers derived from plant cellulose to obtain information vital both for the future usage of these materials in agribusiness and for an understanding of their environmental impacts.Keywords: cotton, curaua, nanotoxicology, environmental nanotechnology

  8. Understanding your colon cancer risk

    Science.gov (United States)

    Colon cancer - prevention; Colon cancer - screening ... We do not know what causes colon cancer, but we do know some of the things that may increase the risk of getting it, such as: Age. Your risk increases ...

  9. 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.

  10. Human biological monitoring of occupational genotoxic exposures

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Sorsa, M

    1993-01-01

    for and the biomonitoring results should preferentially be linked with accurate ambient air monitoring. In persons occupationally exposed to styrene the endpoints of DNA-damage and DNA-repair in genetic monitoring are methods of choice in exposure situations above the current Danish (25 ppm) or Finnish (20 ppm......) occupational exposure limit value of styrene in ambient air. The consideration of ethical issues in human genetic monitoring is an important but often overlooked aspect. This includes the scientific and preventional relevance of performing a test on individuals, pre- and post study information of donors......Human biological monitoring is a valuable tool for exposure assessment in groups of persons occupationally exposed to genotoxic agents. If the monitoring activity covers genetic material the term genetic monitoring is used. The methods used for genetic monitoring are either substance specific, e...

  11. In vitro genotoxicity of pyridine in human lymphocytes.

    Science.gov (United States)

    Emelnsia, Aida D; Rather, Irfan A

    2016-05-01

    This work was carried out to study the genotoxicity of pyridine in vitro on human leucocyte culture. Cyclophosphamide, a well-known carcinogen was used as positive control. The four different concentrations of pyridine and cyclophosphamide showed breaks and pulverization of chromosomes in dose dependent manner. Higher number of pulverization was observed with higher concentration of pyridine (3.25μg/mL). Based on this data, our results confirm that both pyridine and its precursor showed genotoxicity against human lymphocytes.

  12. Sonography in Colonic Diverticulitis

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Mi Yun; Choi, Byung Hun; Kim, Keum Won; Kwon, Kwi Ryun; Lim, Myung Ah; Kim, Sung Soo; Choi, Chang Ho [Sunlin Presbyterian Hospital, Pohang (Korea, Republic of)

    1996-06-15

    To evaluate the sonographic findings and the diagnostic value of colonic diverticulitis. We evaluated the sonograms of 26 patients with colonic diverticulitis retrospectively. The final diagnosis was based on the pathologic interpretation of a surgical specimen (5 cases), clinical course (21 cases), on barium enema (12 cases) and colonoscopy (1 case). Twenty-five patients had acute diverticulitis in the cecum and 1 patient in the descending colon. On sonography, an oval or short tubular focus which protruded from the colonic wall was seen in 23 patients (88%) and the longest diameter were from 0.5 cm to 3 cm (mean 1.4cm). The lesions were echogenic in 8 cases and hypoechoic in 17 cases. Segmental thickening of the colonic wall was seen in 13 patients (50%), of these, protruding focus was seen in 92%. Pericolic abscess located inposterolateral and medial portion to the colon was seen in 11 patients (42%). Infiltration in pericolic fat(50%), enlargement of pericolic lymph nodes (27%) and small pericolic fluid (8%) were also seen. Our results show that ultrasonography is useful technique in the diagnosis of colonic diverticulitis and in the differentiation from acute appendicitis

  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. CT Findings of Colonic Complications Associated with Colon Cancer

    OpenAIRE

    Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Young Tong; Kim, Chang-Jin

    2010-01-01

    A broad spectrum of colonic complications can occur in patients with colon cancer. Clinically, some of these complications can obscure the presence of underlying malignancies in the colon and these complications may require emergency surgical management. The complications of the colon that can be associated with colon cancer include obstruction, perforation, abscess formation, acute appendicitis, ischemic colitis and intussusception. Although the majority of these complications only rarely oc...

  15. Laparoscopic Colon Resection

    Science.gov (United States)

    ... thorough evaluation by a surgeon qualified in laparoscopic colon resection in consultation with your primary ... Olympic Blvd., Suite 600 Los Angeles, CA 90064 Tel: (310) 437-0544 Fax: (310) 437- ...

  16. Colonic potassium handling

    DEFF Research Database (Denmark)

    Sørensen, Mads Vaarby; Matos, Joana E.; Prætorius, Helle;

    2010-01-01

    regulated by hormones and adapts readily to changes in dietary K+ intake, aldosterone and multiple local paracrine agonists. In chronic renal insufficiency, colonic K+ secretion is greatly enhanced and becomes an important accessory K+ excretory pathway. During severe diarrheal diseases of different causes......, intestinal K+ losses caused by activated ion secretion may become life threatening. This topical review provides an update of the molecular mechanisms and the regulation of mammalian colonic K+ absorption and secretion. It is motivated by recent results, which have identified the K+ secretory ion channel...... in the apical membrane of distal colonic enterocytes. The directed focus therefore covers the role of the apical Ca2+ and cAMP-activated BK channel (KCa1.1) as the apparently only secretory K+ channel in the distal colon....

  17. Adenocarcinoma in Colonic Interposition

    Directory of Open Access Journals (Sweden)

    Shahar Grunner

    2013-03-01

    Full Text Available A 59-year-old female with dysphagia presented to our clinic. In childhood, she underwent colonic interposition due to anastomotic stricture after a previous proximal gastrectomy for gastric ulcer perforation. Imaging studies revealed a space-occupying lesion obstructing the distal interposed colon. At surgery, completion gastrectomy with segmental colectomy was carried out, and Roux-en-Y coloenterostomy and enteroenterostomy were performed.

  18. A sucrose-rich diet induces mutations in the rat colon

    DEFF Research Database (Denmark)

    Dragsted, Lars O.; Daneshvar, Bahram; Vogel, Ulla

    2002-01-01

    affecting the overall energy and carbohydrate intake. We observed a dose-dependent increase in the mutation frequency at the cII site in the colonic mucosa with increased sucrose levels, reaching a 129% increase at the highest dose level. This would indicate a direct or indirect genotoxic effect...... of a sucrose-rich diet. No significant increase in mutations was observed in the liver. To seek an explanation for this finding, a variety of parameters were examined representing different mechanisms, including increased oxidative stress, changes in oxidative defense, effects on DNA repair, or changes......, but the background level of DNA adducts (I-compounds) as determined by (32)P postlabeling was significantly decreased in colon. This decrease in colon I-compounds correlated inversely with both mutation frequency and ERCC1 DNA repair gene expression. Dietary sucrose did not change liver apoptosis or cell turnover...

  19. Genotoxicity and carcinogenicity risk of carbon nanotubes.

    Science.gov (United States)

    Toyokuni, Shinya

    2013-12-01

    Novel materials are often commercialized without a complete assessment of the risks they pose to human health because such assessments are costly and time-consuming; additionally, sometimes the methodology needed for such an assessment does not exist. Carbon nanotubes have the potential for widespread application in engineering, materials science and medicine. However, due to the needle-like shape and high durability of multiwalled carbon nanotubes (MWCNTs), concerns have been raised that they may induce asbestos-like pathogenicity when inhaled. Indeed, experiments in rodents supported this hypothesis. Notably, the genetic alterations in MWCNT-induced rat malignant mesothelioma were similar to those induced by asbestos. Single-walled CNTs (SWCNTs) cause mitotic disturbances in cultured cells, but thus far, there has been no report that SWCNTs are carcinogenic. This review summarizes the recent noteworthy publications on the genotoxicity and carcinogenicity of CNTs and explains the possible molecular mechanisms responsible for this carcinogenicity. The nanoscale size and needle-like rigid structure of CNTs appear to be associated with their pathogenicity in mammalian cells, where carbon atoms are major components in the backbone of many biomolecules. Publishing adverse events associated with novel materials is critically important for alerting people exposed to such materials. CNTs still have a bright future with superb economic and medical merits. However, appropriate regulation of the production, distribution and secondary manufacturing processes is required, at least to protect the workers.

  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. 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.

  2. Analysis of Delphinidin and Luteolin Genotoxicity in Human Lymphocyte Culture

    Directory of Open Access Journals (Sweden)

    Jasmin Ezić

    2015-08-01

    Full Text Available Introduction: Bioflavonoids delphinidin (2-(3,4,5-Trihydroxyphenylchromenylium-3,5,7-triol and luteolin (2-(3,4-Dihydroxyphenyl-5,7-dihydroxy-4-chromenone have been recognized as promising antioxidants and anticancer substances. Due to their extensive use, the goal of the research was to determine whether they have any genotoxic potential in vitro.Methods: Analysis of genotoxic potential was performed applying chromosome aberrations test in human lymphocyte culture, as this kind of research was not conducted abundantly for these two bioflavonoids. Delphinidin and luteolin were dissolved in DMSO and added to cultures in final concentrations of 25, 50 and 100 μM.Results: In human lymphocytes cultures Delphinidin induced PCDs in all treatments, potentially affecting the cell cycle and topoisomerase II activity. In concentration of 50 μM luteolin showed strong genotoxic effects and caused significant reduction of cell proliferation.Conclusion: Luteolin exhibited certain genotoxic and cytostatic potential. Delphinidin was not considered genotoxic, however its impact on mitosis, especially topoisomerase II activity, was revealed.

  3. Genotoxic risk in rubber manufacturing industry: a systematic review.

    Science.gov (United States)

    Bolognesi, Claudia; Moretto, Angelo

    2014-10-15

    A large body of evidence from epidemiological studies among workers employed in the rubber manufacturing industry has indicated a significant excess cancer risk in a variety of sites. The International Agency for Research on Cancer has recently classified the "Occupational exposures in the rubber-manufacturing industry" as carcinogenic to humans (Group 1). A genotoxic mechanism for the increased cancer risk was suggested on the basis of the evidence from the scientific literature. Exposure assessment studies have shown that workers in the rubber manufacturing industry may be exposed to different airborne carcinogenic and/or genotoxic chemicals, such as certain aromatic amines, polycyclic aromatic hydrocarbons, N-nitrosamines, although the available information does not allow to establish a causal association of cancer or genotoxic risk with particular substances/classes of chemicals or specific jobs. The aim of this paper is to critically evaluate, by conducting a systematic review, the available biomonitoring studies using genotoxicity biomarkers in rubber manufacturing industry. This systematic review suggests that a genotoxic hazard may still be present in certain rubber manufacturing industries. A quantitative risk assessment needs further studies addressing the different, processes and chemicals in the rubber manufacturing industries.

  4. Evaluation of genotoxicity testing of FDA approved large molecule therapeutics.

    Science.gov (United States)

    Sawant, Satin G; Fielden, Mark R; Black, Kurt A

    2014-10-01

    Large molecule therapeutics (MW>1000daltons) are not expected to enter the cell and thus have reduced potential to interact directly with DNA or related physiological processes. Genotoxicity studies are therefore not relevant and typically not required for large molecule therapeutic candidates. Regulatory guidance supports this approach; however there are examples of marketed large molecule therapeutics where sponsors have conducted genotoxicity studies. A retrospective analysis was performed on genotoxicity studies of United States FDA approved large molecule therapeutics since 1998 identified through the Drugs@FDA website. This information was used to provide a data-driven rationale for genotoxicity evaluations of large molecule therapeutics. Fifty-three of the 99 therapeutics identified were tested for genotoxic potential. None of the therapeutics tested showed a positive outcome in any study except the peptide glucagon (GlucaGen®) showing equivocal in vitro results, as stated in the product labeling. Scientific rationale and data from this review indicate that testing of a majority of large molecule modalities do not add value to risk assessment and support current regulatory guidance. Similarly, the data do not support testing of peptides containing only natural amino acids. Peptides containing non-natural amino acids and small molecules in conjugated products may need to be tested.

  5. On the relationship between sialomucin and sulfomucin expression and hydrogenotrophic microbes in the human colonic mucosa.

    Directory of Open Access Journals (Sweden)

    Jennifer A Croix

    Full Text Available The colonic mucus layer is comprised primarily of acidomucins, which provide viscous properties and can be broadly classified into sialomucins or sulfomucins based on the presence of terminating sialic acid or sulfate groups. Differences in acidomucin chemotypes have been observed in diseases such as colorectal cancer and inflammatory bowel disease, and variation in sialo- and sulfomucin content may influence microbial colonization. For example, sulfate derived from sulfomucin degradation may promote the colonization of sulfate-reducing bacteria (SRB, which through sulfate respiration generate the genotoxic gas hydrogen sulfide. Here, paired biopsies from right colon, left colon, and rectum of 20 subjects undergoing routine screening colonoscopies were collected to enable parallel histochemical and microbiological studies. Goblet cell sialo- and sulfomucins in each biopsy were distinguished histochemically and quantified. Quantitative PCR and multivariate analyses were used to examine the abundance of hydrogenotrophic microbial groups and SRB genera relative to acidomucin profiles. Regional variation was observed in sialomucins and sulfomucins with the greatest abundance of each found in the rectum. Mucin composition did not appear to influence the abundance of SRB or other hydrogenotrophic microbiota but correlated with the composition of different SRB genera. A higher sulfomucin proportion correlated with higher quantities of Desulfobacter, Desulfobulbus and Desulfotomaculum, relative to the predominant Desulfovibrio genus. Thus, acidomucin composition may influence bacterial sulfate respiration in the human colon, which may in turn impact mucosal homeostasis. These results stress the need to consider mucus characteristics in the context of studies of the microbiome that target intestinal diseases.

  6. Inflammation and colon cancer.

    Science.gov (United States)

    Terzić, Janos; Grivennikov, Sergei; Karin, Eliad; Karin, Michael

    2010-06-01

    The connection between inflammation and tumorigenesis is well-established and in the last decade has received a great deal of supporting evidence from genetic, pharmacological, and epidemiological data. Inflammatory bowel disease is an important risk factor for the development of colon cancer. Inflammation is also likely to be involved with other forms of sporadic as well as heritable colon cancer. The molecular mechanisms by which inflammation promotes cancer development are still being uncovered and could differ between colitis-associated and other forms of colorectal cancer. Recent work has elucidated the role of distinct immune cells, cytokines, and other immune mediators in virtually all steps of colon tumorigenesis, including initiation, promotion, progression, and metastasis. These mechanisms, as well as new approaches to prevention and therapy, are discussed in this review.

  7. Congenital Pouch Colon

    Directory of Open Access Journals (Sweden)

    Vivek Gharpure

    2012-07-01

    Full Text Available Face The Examiner:QUESTIONS1. What are the diagnostic features of congenital pouch colon (CPC?Ans: A male patient with CPC often have a wide colovesical fistula and present with anorectal malformation and meconuria; on plain abdominal film, a single large bowel loop occupying more than 50% of the abdominal cavity is also a diagnostic sign. Girls (persistent cloaca/vestibular fistula/anteriorly placed anus etc. often present late with intractable constipation or multiple episodes of enterocolitis and persistent abdominal distension with common cloaca or anterior ectopic anus/ rectovestibular fistula. The congenital pouch colon can be identified as replacement of a part or entire colon in the configuration of pouch that lacks taenia coli, haustrations, appendices epiploicae, abnormal blood supply and a wide fistula with genitourinary system in a patient of anorectal malformation.

  8. CT findings of colonic diverticulitis

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Shigeru; Ohba, Satoru [Nagoya City Univ. (Japan). Medical School; Mizutani, Masaru [and others

    1998-11-01

    Although colonic diverticulitis has no indication for operation, but in some mistaken cases were operated with a diagnosis of acute appendicitis. We evaluated the CT findings of colonic diverticulitis about 19 cases and of asymptomatic colonic diverticula about 15 cases retrospectively. Diagnosis was confirmed of barium enema and operation. CT are complementary methods of examination that can delineated the range of thickening of the colon and the extension of inflammatory changes around the colon. We also believe that CT findings of colonic diverticulitis are useful for differentiating from a diagnosis of appendicitis. (author)

  9. Recent trend of colonic diverticulosis

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Yae Soon; Lee, Sung Woo; Han, Chang Yul; Lee, Kwan Seh [Inje Medical College, Seoul (Korea, Republic of)

    1988-08-15

    Colonic Diverticulosis is once thought to be a rare disease in Korea compared with western countries, but the incidence has been increasing with passage of time. Authors reviewed 151 cases of colon study with new double contrast method performed from November, 1986 to March, 1987 at Paik Hospital Inje college. The results were as follow: 1. The colonic diverticulosis was found in 39 cases out of 151 colon study (25.8%). 2. Colonic Diverticulosis were located at right and transvercolon in 54% and left and sigmoid colon in 18%. 3. Increasing occurrence in younger age group predilection; 4th decade was observed.

  10. Genotoxicity of unmodified and organo-modified montmorillonite

    DEFF Research Database (Denmark)

    Sharma, Anoop Kumar; Schmidt, Bjørn; Frandsen, Henrik Lauritz;

    2010-01-01

    The natural clay mineral montmorillonite (Cloisite (R) Na+) and an organo-modified montmorillonite (Cloisite (R) 30B) were investigated for genotoxic potential as crude suspensions and as suspensions filtrated through a 0.2-mu m pore-size filter to remove particles above the nanometre range...... absent in the filtered samples, which was independently confirmed by dynamic light-scattering measurements. Detection and identification of free quaternary ammonium modifier in the filtered sample was carried out by HPLC-Q-TOF/MS and revealed a total concentration of a mixture of quaternary ammonium...... analogues of 1.57 mu g/ml. These findings suggest that the genotoxicity of organo-modified montmorillonite was caused by the organo-modifier. The detected organo-modifier mixture was synthesized and comet-assay results showed that the genotoxic potency of this synthesized organo-modifier was in the same...

  11. 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.

  12. Investigations of potential susceptibility toward formaldehyde-induced genotoxicity.

    Science.gov (United States)

    Zeller, Jasmin; Högel, Josef; Linsenmeyer, Regina; Teller, Christopher; Speit, Günter

    2012-09-01

    Blood samples were taken from three groups of volunteers (30 male smokers, 30 female non-smokers, and 30 school children) and tested for ex vivo susceptibility toward formaldehyde (FA)-induced genotoxicity. Blood samples were exposed to 150 μM FA for 2 h, and the induction of DNA-protein crosslinks (DPX) in leukocytes was measured by a modification of the alkaline comet assay (i.e., reduction of γ-irradiation induced DNA migration). Removal of DPX was determined by the abolition of FA-induced reduction in DNA migration within 4 h after the end of the exposure. Induction and persistence of FA-induced DNA lesions was also measured by the sister chromatid exchange (SCE) test with cultured lymphocytes after treatment of whole blood cultures with FA (150 μM). Furthermore, the expression (mRNA level) of the GSH-dependent formaldehyde dehydrogenase (FDH, identical to alcohol dehydrogenase 5; ADH5) was measured in leukocytes by quantitative real-time RT-PCR with TaqMan probes. The subjects were also analyzed for the GSTM1 and GSTT1 metabolic gene polymorphisms and a correlation analysis with the investigated genetic endpoints for FA-induced genotoxicity was performed. The results indicate that there are no biologically relevant differences between the three study groups with regard to the various indicators of cellular sensitivity toward FA-induced genotoxic effects and the expression of FDH. The induced genotoxic effects were not associated with polymorphisms in GSTM1 and GSTT1. None of the study groups showed particular mutagen sensitivity toward FA-induced genotoxicity. These results suggest that a low scaling factor to address possible human inter-individual differences in FA-induced genotoxicity could be reasonable.

  13. Genotoxicity of diuron and glyphosate in oyster spermatozoa and embryos.

    Science.gov (United States)

    Akcha, F; Spagnol, C; Rouxel, J

    2012-01-15

    We investigated the effects of genotoxicant exposure in gametes and embryos to find a possible link between genotoxicity and reproduction/developmental impairment, and explore the impact of chemical genotoxicity on population dynamics. Our study focused on the genotoxic effects of two herbicides on oyster gametes and embryos: glyphosate (both as an active substance and in the Roundup formulation) and diuron. France is Europe's leading consumer of agrochemical substances and as such, contamination of France's coastal waters by pesticides is a major concern. Glyphosate and diuron are among the most frequently detected herbicides in oyster production areas; as oyster is a specie with external reproduction, its gametes and embryos are in direct contact with the surrounding waters and are hence particularly exposed to these potentially dangerous substances. In the course of this study, differences in genotoxic and embryotoxic responses were observed in the various experiments, possibly due to differences in pollutant sensitivity between the tested genitor lots. Glyphosate and Roundup had no effect on oyster development at the concentrations tested, whereas diuron significantly affected embryo-larval development from the lowest tested concentration of 0.05 μg L⁻¹, i.e. an environmentally realistic concentration. Diuron may therefore have a significant impact on oyster recruitment rates in the natural environment. Our spermiotoxicity study revealed none of the tested herbicides to be cytotoxic for oyster spermatozoa. However, the alkaline comet assay showed diuron to have a significant genotoxic effect on oyster spermatozoa at concentrations of 0.05 μg L⁻¹ upwards. Conversely, no effects due to diuron exposure were observed on sperm mitochondrial function or acrosomal membrane integrity. Although our initial results showed no negative effect on sperm function, the possible impact on fertilization rate and the consequences of the transmission of damaged DNA for

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    Satomi Kawaguchi

    2010-01-01

    Full Text Available 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 human lymphoblastoid cells were exposed to methyl nitrosourea (MNU, ethyl nitrosourea (ENU, methyl methanesulfonate (MMS, ethyl methanesulfonate (EMS, bleomycin (BLM, or UVC. In Comet assay, cells were exposed to each mutagen with (Comet assay/araC and without (Comet assay DNA repair inhibitors (araC and hydroxyurea. Furthermore, acellular Comet assay (acellular assay was performed to determine how single-strand breaks (SSBs as the initial damage contributes to DNA migration and/or to micronucleus formation. The lowest genotoxic dose (LGD, which is defined as the lowest dose at which each mutagen causes a positive response on each genotoxicity assay, was used to compare the power of the Comet assay to detect a low level of genotoxic potential and that of MN test; that is, a low LGD indicates a high power. Results are summarized as follows: (1 for all mutagens studied, LGDs were MN test ≦ Comet assay; (2 except for BLM, LGDs were Comet assay/araC ≦ MN test; (3 except for UVC and MNU, LGDs were acellular assay ≦ Comet assay/araC ≦ MN test ≦ Comet assay. The following is suggested by the present findings: (1 LGD in the Comet assay is higher than that in MN test, which suggests that the power of the MN test to detect a low level of genotoxic potential is superior to that of the Comet assay; (2 for the studied mutagens, all assays were able to detect all mutagens correctly, which suggests that the sensitivity of the Comet assay and that of the MN test were

  16. A central role for heme iron in colon carcinogenesis associated with red meat intake.

    Science.gov (United States)

    Bastide, Nadia M; Chenni, Fatima; Audebert, Marc; Santarelli, Raphaelle L; Taché, Sylviane; Naud, Nathalie; Baradat, Maryse; Jouanin, Isabelle; Surya, Reggie; Hobbs, Ditte A; Kuhnle, Gunter G; Raymond-Letron, Isabelle; Gueraud, Françoise; Corpet, Denis E; Pierre, Fabrice H F

    2015-03-01

    Epidemiology shows that red and processed meat intake is associated with an increased risk of colorectal cancer. Heme iron, heterocyclic amines, and endogenous N-nitroso compounds (NOC) are proposed to explain this effect, but their relative contribution is unknown. Our study aimed at determining, at nutritional doses, which is the main factor involved and proposing a mechanism of cancer promotion by red meat. The relative part of heme iron (1% in diet), heterocyclic amines (PhIP + MeIQx, 50 + 25 μg/kg in diet), and NOC (induced by NaNO₂+ NaNO₂; 0.17 + 0.23 g/L of drinking water) was determined by a factorial design and preneoplastic endpoints in chemically induced rats and validated on tumors in Min mice. The molecular mechanisms (genotoxicity, cytotoxicity) were analyzed in vitro in normal and Apc-deficient cell lines and confirmed on colon mucosa. Heme iron increased the number of preneoplastic lesions, but dietary heterocyclic amines and NOC had no effect on carcinogenesis in rats. Dietary hemoglobin increased tumor load in Min mice (control diet: 67 ± 39 mm²; 2.5% hemoglobin diet: 114 ± 47 mm², P = 0.004). In vitro, fecal water from rats given hemoglobin was rich in aldehydes and was cytotoxic to normal cells, but not to premalignant cells. The aldehydes 4-hydroxynonenal and 4-hydroxyhexenal were more toxic to normal versus mutated cells and were only genotoxic to normal cells. Genotoxicity was also observed in colon mucosa of mice given hemoglobin. These results highlight the role of heme iron in the promotion of colon cancer by red meat and suggest that heme iron could initiate carcinogenesis through lipid peroxidation. .

  17. Treatment Option Overview (Colon Cancer)

    Science.gov (United States)

    ... Colorectal Cancer Colorectal Cancer Screening Research Colon Cancer Treatment (PDQ®)–Patient Version General Information About Colon Cancer ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  18. 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 results concerning of positive findings by micronuclei and non significant ones by comet assay, are corroborated by Deng et al. (2005 study performed in workers occupationally exposed to methotrexate, also a cytostatic drug. According to Cavallo et al. (2009, the comet assay seems to be more suitable for the prompt evaluation of the genotoxic effects, for instance, of polycyclic aromatic hydrocarbons mixtures containing volatile substances, whereas the micronucleus test seems more appropriate to evaluate the effects of exposure to antineoplastic agents. However, there are studies that observed an increase in both the comet assay and the micronucleus test in nurses handling antineoplastic drugs, although statistical significance was only seen in the comet assay, quite the opposite of our results (Maluf & Erdtmann, 2000; Laffon et al. 2005.

  19. Stages of Colon Cancer

    Science.gov (United States)

    ... The PDQ summaries are based on an independent review of the medical literature. They are not policy statements of the NCI or the NIH. Purpose of This Summary This PDQ cancer information summary has current information about the treatment of colon cancer. It is meant to inform and help ...

  20. Spontaneous transverse colon volvulus.

    Science.gov (United States)

    Sana, Landolsi; Ali, Gassara; Kallel, Helmi; Amine, Baklouti; Ahmed, Saadaoui; Ali, Elouer Mohamed; Wajdi, Chaeib; Saber, Mannaï

    2013-01-01

    We report a case of spontaneous transverse colon volvulus in a young healthy woman. It constitutes an unusual case since it occurred in a young healthy woman with a subacute onset and no aetiological factor has been found. Its diagnosis is still challenging. Prompt recognition with emergency intervention constitutes the key to successful outcome.

  1. Colonization, mouse-style

    Directory of Open Access Journals (Sweden)

    Searle Jeremy B

    2010-10-01

    Full Text Available Abstract Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice. See research article: http://www.biomedcentral.com/1471-2148/10/325

  2. Understanding Antegrade Colonic Enema (ACE) Surgery

    Science.gov (United States)

    ... Enema (ACE) Surgery Understanding Antegrade Colonic Enema (ACE) Surgery Antegrade colonic enema surgery (ACE) or Malone antegrade ... Email Print What is antegrade colonic enema (ACE) surgery? Antegrade colonic enema surgery (ACE) or Malone antegrade ...

  3. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... collection below explain colon cancer risk factors, screening tests, and treatments. There are also personal stories from ... Colon Cancer Risk Play Play Colon Cancer: Screening Tests Play Play Colon Cancer Screening Tests: Colonoscopy Play ...

  4. 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.

  5. 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.

  6. External coating of colonic anastomoses

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Achiam, Michael Patrick; Rosenberg, Jacob

    2012-01-01

    Colon anastomotic leakage remains both a frequent and serious complication in gastrointestinal surgery. External coating of colonic anastomoses has been proposed as a means to lower the rate of this complication. The aim of this review was to evaluate existing studies on external coating of colonic...

  7. 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.

  8. Genotoxic Maillard byproducts in current phytopharmaceutical preparations of Echinodorus grandiflorus

    Directory of Open Access Journals (Sweden)

    ELISANGELA C. LIMA-DELLAMORA

    2014-09-01

    Full Text Available Extracts of Echinodorus grandiflorus obtained from dried leaves by three different techniques were evaluated by bacterial lysogenic induction assay (Inductest in relation to their genotoxic properties. Before being added to test cultures, extracts were sterilized either by steam sterilization or ultraviolet light. Only the extracts prepared by infusion and steam sterilized have shown genotoxic activity. The phytochemical analysis revealed the presence of the flavonoids isovitexin, isoorientin, swertisin and swertiajaponin, isolated from a genotoxic fraction. They were assayed separately and tested negative in the Inductest protocol. The development of browning color and sweet smell in extracts submitted to heat, prompted further chemical analysis in search for Maillard's reaction precursors. Several aminoacids and reducing sugars were cast in the extract. The presence of characteristic Maillard's melanoidins products was determined by spectrophotometry in the visible region and the inhibition of this reaction was observed when its characteristic inhibitor, sodium bisulfite, was added prior to heating. Remarkably, this is the first paper reporting on the appearance of such compounds in a phytomedicine preparation under a current phytopharmaceutical procedure. The genotoxic activity of such heat-prepared infusions imply in some risk of developing degenerative diseases for patients in long-term, uncontrolled use of such phytomedicines.

  9. 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.

  10. 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

  11. 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.

  12. Genotoxicity studies on a high-purity rebaudioside A preparation.

    Science.gov (United States)

    Williams, Lonnie D; Burdock, George A

    2009-08-01

    Rebaudioside A (Reb A) is a steviol glycoside isolated from the leaves of the Stevia rebaudiana plant. This non-nutritive, natural sweetener is reported to be 250-450 times sweeter than sucrose and has potential for wide use in the US diet, and is used in Japan and South America today. The safety of Reb A has been investigated in several recently published studies and information on genotoxicity is described herein. Reb A was investigated for its potential to induce genotoxicity in three in vitro and two in vivo assays (conducted according to OECD guidelines). Reb A was non-mutagenic in an Ames test using Salmonella typhimurium and Escherichia coli, in a chromosomal aberration test using Chinese Hamster V79 cells and in a mouse lymphoma assay using L5178Y+/- cells, all studies were conducted at concentrations up to 5000 microg/ml, with and without metabolic activation. Also, Reb A was non-genotoxic in a bone marrow micronucleus test in mice at doses up 750 mg/kg bw and in an unscheduled DNA synthesis test in rats at 2000 mg/kg bw. These studies provide additional evidence that Reb A is not genotoxic at the doses tested and further support the generally recognized as safe determination of Reb A.

  13. Association between CYP7A1 and the risk of proximal colon cancer in Japanese.

    Science.gov (United States)

    Ito, Hidemi; Matsuo, Keitaro; Hosono, Satoyo; Watanabe, Miki; Kawase, Takakazu; Suzuki, Takeshi; Hirai, Takashi; Yatabe, Yasushi; Tanaka, Hideo; Tajima, Kazuo

    2010-01-01

    Bile acids have long been implicated in the etiology of colorectal carcinogenesis by their genotoxicity as well as cytotoxicity. Cholesterol 7-alfa-hydroxylase (CYP7A1) is the rate-limiting enzyme that converts cholesterol into cholesterol 7-alfa-hydroxycholesterol in the first step of the classical pathway of bile acid synthesis. Recently, an association between a polymorphism (-204A>C, rs3808607) in CYP7A1 and proximal colon cancer/adenoma has been reported, which was not observed with distal colon or rectal cancer/adenoma. In this case-control study, we examined the association between haplotypes of CYP7A1 and proximal or distal colon/rectal cancer risk in a Japanese population. Subjects were 96 cases of proximal colon cancer, 357 of distal colon/rectal cancer and 961 age- and sex-matched non-cancer controls at Aichi Cancer Center. We examined five loci, including rs3808607, and evaluated the impact of haplotype on risk. In locus-specific analyses, we saw no association with rs3808607 for any site. Haplotype analyses revealed that the TAAGG haplotype was positively associated with proximal colon cancer [confounder-adjusted odds ratio: 1.72 (95% confidence interval: 1.10-2.71), p=0.018] but not with distal colon and rectal cancer combined. This association was consistently observed in analyses stratified by potential confounders. Our results indicate that CYP7A1 plays a role in the carcinogenesis of colorectal cancer specifically in the proximal colon. Confirmation of this association in other epidemiologic studies and biological evaluation of the TAAGG haplotype are warranted.

  14. Sonographic Features of Colonic Diverticulitis

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Yu Mee; Ko, Young Tae; Lim, Joo Won; Lee, Dong Ho; Yoon, Yup [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    1996-06-15

    To evaluate sonographic features, location of diverticulum, and usefulness of sonography as a primary diagnostic tool. Sonographic findings of 28 patients with acute diverticulitis were reviewed. The diagnosis was made by surgery (11 patients), barium enema (20 patients), colonoscopy (3 patients), or CT (2 patients). There were 13 men and 15 women with ages ranging from 23 to 71 years old (mean, 33 years old). Sonographic abnormalities were seen in the cecum in 12 patients, both the cecum and ascending colon in seven, the ascending colon in six, the descending colon in two, and the transverse colon in one. On sonography, segmental thickening of the colonic wall was the most common finding, seen in 16 patients. The second most common finidngs were pericolic omental thickening and pericolic localized fluid collection (15 patients). Pericolic inflammatory mass of varying echogenicity (10 patients), out pouching hyper echoic foci beyond the lumen of the colon into or beyond the thickened wall (5 patients), contracture of the colon (5 patients), slightly thickened terminal ileum (1 patient), and local enlargement of ileocecal lymph node (1 patient) were also seen. Most diverticulitis occurred in the right colon. The useful sonographic findings in acute diverticulitis were echogenic foci of the diverticulum in the thickened colonic wall, focally and eccentrically thickened colonic wall, and localized omental thickening or fluid collection. In cases of pericecal fluid collection, appendicitis or colonic diverticulitis can be considered as a differential diagnosis

  15. Genotoxicity in native fish associated with agricultural runoff events

    Science.gov (United States)

    Whitehead, A.; Kuivila, K.M.; Orlando, J.L.; Kotelevtsev, S.; Anderson, S.L.

    2004-01-01

    The primary objective of the present study was to test whether agricultural chemical runoff was associated with in-stream genotoxicity in native fish. Using Sacramento sucker (Catostomus occidentalis), we combined field-caging experiments in an agriculturally dominated watershed with controlled laboratory exposures to field-collected water samples, and we coupled genotoxicity biomarker measurements in fish with bacterial mutagenicity analysis of water samples. We selected DNA strand breakage as a genotoxicity biomarker and Ames Salmonella mutagenicity tests as a second, supporting indicator of genotoxicity. Data from experiments conducted during rainfall runoff events following winter application of pesticides in 2000 and 2001 indicated that DNA strand breaks were significantly elevated in fish exposed to San Joaquin River (CA, USA) water (38.8, 28.4, and 53.6% DNA strand breakage in year 2000 field, year 2000 lab, and year 2001 field exposures, respectively) compared with a nearby reference site (15.4, 8.7, and 12.6% DNA strand breakage in year 2000 field, year 2000 lab, and year 2001 field exposures, respectively). Time-course measurements in field experiments supported a linkage between induction of DNA strand breakage and the timing of agricultural runoff. San Joaquin River water also caused significant reversion mutation in two Ames Salmonella tester strains. Salmonella mutagenicity corroborated in-stream effects, further strengthening a causal relationship between runoff events and genotoxicity. Potentially responsible agents are discussed in the context of timing of runoff events in the field, concordance between laboratory and field exposures, pesticide application patterns in the drainage, and analytical chemistry data.

  16. Nonobstructing Colonic Dilatation and Colon Perforations Following Renal Transplantation

    Science.gov (United States)

    Koneru, Baburao; Selby, Rick; O’Hair, Daniel P.; Tzakis, Andreas G.; Hakala, Thomas R.; Starzl, Thomas E.

    2010-01-01

    Nonobstructing colonic dilatation has not been commonly reported following renal transplantation, and colon perforations carry a high morbidity and mortality in this population. During a 7-year period, nonobstructing colonic dilatation developed in 13 adults 1 to 13 days after renal transplantation. Twelve (92%) of the 13 had poorly functioning allografts. Five (83%) of the 6 with and 2 (29%) of the 7 without colonoscopy had resolution of nonobstructing colonic dilatation. Of the seven right-sided colon perforations during this period, six were associated with nonobstructing colonic dilatation. An additional 4 patients had diverticular perforations in the left colon. Of a total of 11 patients with colon perforation, 7 had surgery within 24 hours of the perforation and 6 (86%) of these survived. Only 1 (25%) of the 4 having surgery more than 24 hours later survived. Six of the survivors retained functioning allografts. Nonobstructing colonic dilatation seems to be a potential complication of poor graft function after renal transplantation, and colonoscopy is effective in its treatment. In patients with colon perforations, early surgery and reduced immunosuppression are essential in decreasing mortality. PMID:2331220

  17. Phytochemical study and evaluation of cytotoxic and genotoxic properties of extracts from Clusia latipes leaves

    Directory of Open Access Journals (Sweden)

    Natalia Bailón-Moscoso

    2016-02-01

    Full Text Available Abstract Some species of the Clusia genus have been shown to have important biomedical properties, including the ability to inhibit tumor growth in vitro and the usefulness for skin care. In this study, we examined the cytotoxic effect of hexane, ethyl acetate and methanol extracts from Clusia latipes Planch. & Triana, Clusiaceae, leaves on survival of human prostate cancer cells (PC-3, colon cancer cells (RKO, astrocytoma cells (D-384, and breast cancer cells (MCF-7. The ethyl acetate extract displayed the most substantial cytotoxic effect. However, using a Comet assay, we observed that the hexane extract induced a genotoxic effect (DNA damage on human lymphocytes in an in vitro model. Chromatographic purification of the C. latipes hexane extract led to the isolation and identification of friedelin, friedolan-3-ol, and hesperidin as active cytotoxic compounds in hexane extract, while β-amyrine was identified as an active cytotoxic compound in the ethyl acetate extract of C. latipes, thereby supporting further studies of the molecular mechanisms underlying the effect of these secondary metabolites on cancer cell survival.

  18. Giant colon lipoma.

    Science.gov (United States)

    Yaman, İsmail; Derici, Hayrullah; Demirpolat, Gülen

    2015-01-01

    Colon lipomas are rare, non-epithelial tumors. They are generally smaller than two centimeters and asymptomatic, they are incidentally diagnosed and do not require treatment. Large and symptomatic colon lipomas are rather rare. Its differential diagnosis is generally made by histopathological examination of the resected specimen. A fifty-year-old female patient presented with the symptoms of abdominal pain, swelling in the abdomen and loss of weight. During colonoscopy, there was a submucosal mass of 8×6 cm, which almost completely obstructed the lumen in the hepatic flexure and was covered by a mucosa that was sporadically ulcerated and necrotic in nature. In magnetic resonance imaging, an ovoid mass with a diameter of 8.5 cm at its widest dimension was detected, which had signal intensity similar to that of adipose tissue. Since the patient was symptomatic and differential diagnosis could not be made, she underwent laparoscopic right hemicolectomy. A submucosal lipoma was detected on histopathological examination of the specimen. The patient was discharged without any problems on post-operative day 7. Definite diagnosis of lipomas before surgery is challenging; they may be mistaken for malignancy, especially if the lesion is large and ulcerated. For large and symptomatic colon lipomas, surgery is required to both prevent complications and rule out malignancy.

  19. Neoplasia de colon

    Directory of Open Access Journals (Sweden)

    Alina Torreblanca Xiques

    2014-12-01

    Full Text Available El cáncer de colon es un tumor que se desarrolla por degeneración maligna de las células del intestino grueso, desde la válvula ileocecal hasta la flexura recto sigmoidea. Se presenta el caso de un paciente masculino, de 75 años, con astenia anorexia y pérdida de peso; al examen físico: mucosas hipocoloreadas, abdomen blando no doloroso a la palpación superficial ni profunda. Se palpa aumento de volumen a nivel de la fosa ilíaca derecha, fija, de consistencia dura, ruidos hidroaereos normales. Se realizaron exámenes hematológicos, radiológicos y endoscópicos para el diagnóstico. Se tuvo la confirmación diagnóstica por anatomía patológica de adenocarcinoma de colon derecho, bien diferenciado. Se aplicó tratamiento primario, consistente en una amplia resección quirúrgica del cáncer del colon y el drenaje linfático regional, posteriormente se aplicó quimioterapia. El paciente evolucionó satisfactoriamente

  20. 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

  1. Wheat bran extract alters colonic fermentation and microbial composition, but does not affect faecal water toxicity: a randomised controlled trial in healthy subjects.

    Science.gov (United States)

    Windey, Karen; De Preter, Vicky; Huys, Geert; Broekaert, Willem F; Delcour, Jan A; Louat, Thierry; Herman, Jean; Verbeke, Kristin

    2015-01-28

    Wheat bran extract (WBE), containing arabinoxylan-oligosaccharides that are potential prebiotic substrates, has been shown to modify bacterial colonic fermentation in human subjects and to beneficially affect the development of colorectal cancer (CRC) in rats. However, it is unclear whether these changes in fermentation are able to reduce the risk of developing CRC in humans. The aim of the present study was to evaluate the effects of WBE on the markers of CRC risk in healthy volunteers, and to correlate these effects with colonic fermentation. A total of twenty healthy subjects were enrolled in a double-blind, cross-over, randomised, controlled trial in which the subjects ingested WBE (10 g/d) or placebo (maltodextrin, 10 g/d) for 3 weeks, separated by a 3-week washout period. At the end of each study period, colonic handling of NH3 was evaluated using the biomarker lactose[15N, 15N']ureide, colonic fermentation was characterised through a metabolomics approach, and the predominant microbial composition was analysed using denaturing gradient gel electrophoresis. As markers of CRC risk, faecal water genotoxicity was determined using the comet assay and faecal water cytotoxicity using a colorimetric cell viability assay. Intake of WBE induced a shift from urinary to faecal 15N excretion, indicating a stimulation of colonic bacterial activity and/or growth. Microbial analysis revealed a selective stimulation of Bifidobacterium adolescentis. In addition, WBE altered the colonic fermentation pattern and significantly reduced colonic protein fermentation compared with the run-in period. However, faecal water cytotoxicity and genotoxicity were not affected. Although intake of WBE clearly affected colonic fermentation and changed the composition of the microbiota, these changes were not associated with the changes in the markers of CRC risk.

  2. Diverticulosis in total colonic aganglionosis

    Energy Technology Data Exchange (ETDEWEB)

    Ivancev, K.; Fork, T.; Haegerstrand, I.; Ivarsson, S.; Kullendorff, C.M.

    Two infants with total colonic aganglionosis (TCA) extending into the distal part of the ileum are described. Considerable diagnostic delay occurred with the correct diagnosis established first at 3 and 8 months, respectively. Radiologic findings compatible with TCA such as prolonged barium retention, reflux into ileum following barium enema, and foreshortening of colon were not clearly evident initially. Both patients demonstrated multiple acquired colon diverticula which increased both in number and size during the period of observation. These diverticula are probably a late manifestation of the spastic state of the anganglionic colon. Thus demonstration of diverticula supplies a strong evidence of TCA in infants with intestinal obstruction. (orig.).

  3. 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.

  4. 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

  5. Genotoxicity of Euphorbia hirta: an Allium cepa assay.

    Science.gov (United States)

    Yuet Ping, Kwan; Darah, Ibrahim; Yusuf, Umi Kalsom; Yeng, Chen; Sasidharan, Sreenivasan

    2012-06-26

    The potential genotoxic effects of methanolic extracts of Euphorbia hirta which is commonly used in traditional medicine to treat a variety of diseased conditions including asthma, coughs, diarrhea and dysentery was investigated using Allium cepa assay. The extracts of 125, 250, 500 and 1,000 µg/mL were tested on root meristems of A. cepa. Ethylmethanesulfonate was used as positive control and distilled water was used as negative control. The result showed that mitotic index decreased as the concentrations of E. hirta extract increased. A dose-dependent increase of chromosome aberrations was also observed. Abnormalities scored were stickiness, c-mitosis, bridges and vagrant chromosomes. Micronucleated cells were also observed at interphase. Result of this study confirmed that the methanol extracts of E. hirta exerted significant genotoxic and mitodepressive effects at 1,000 µg/mL.

  6. 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.

  7. Tradescantia micronucleus test indicates genotoxic potential of traffic emissions in European cities

    DEFF Research Database (Denmark)

    Klumpp, A.; Ansel, W.; Klumpp, G.

    2006-01-01

    , the Tradescantia micronucleus (Trad-MCN) test was applied to examine the genotoxicity of urban air pollution. Cuttings of Tradescantia clone #4430 were exposed to ambient air at 65 monitoring sites in 10 conurbations employing a standardised methodology. The tests revealed an elevated genotoxic potential mainly...... is recommended in order to reduce the variability of results due to varying environmental conditions. The Tradescantia micronucleus test can be used to assess genotoxic potential at urban sites....

  8. Cytotoxicity and genotoxicity of phenazine in two human cell lines.

    Science.gov (United States)

    McGuigan, Claire F; Li, Xing-Fang

    2014-06-01

    Phenazine was recently identified as a drinking water disinfection byproduct (DBP), but little is known of its toxic effects. We examined in vitro cytotoxicity and genotoxicity of phenazine (1.9-123 μM) in HepG2 and T24 cell lines. Cytotoxicity was determined by an impedance-based real-time cell analysis instrument. The BrdU (5-bromo-2'-deoxyuridine) proliferation and MTT ((3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) viability assays were used to examine mechanisms of cytotoxicity. Genotoxicity was determined using the alkaline comet assay. Concentration-dependent cytotoxicity was observed in HepG2 cells, primarily due to an antiproliferative effect (BrdU 24 h IC50: 11 μM; 48 h IC50: 7.8 μM) observed as low as 1.9 μM. T24 cells experienced a minor antiproliferative effect (BrdU 24 h IC50: 47 μM; 48 h IC50: 17 μM). IC50 values for HepG2 proliferation and viability were 54-77% lower compared to T24 cells. In both cell lines, IC50 values for proliferation were 66-90% lower than those for viability. At phenazine concentrations producing equivalent cytotoxicity, HepG2 cells (1.9-30.8 μM) experienced no significant genotoxic effects, while T24 cells (7.7-123 μM) experienced significant genotoxicity at ⩾61.5 μM. While these effects were seen at phenazine concentrations above those found in disinfected water, the persistence of the antiproliferative effect and the differential toxicity in each cell line deserves further study.

  9. Genotoxicity of Euphorbia hirta: An Allium cepa Assay

    OpenAIRE

    Kwan Yuet Ping; Ibrahim Darah; Umi Kalsom Yusuf; Chen Yeng; Sreenivasan Sasidharan

    2012-01-01

    The potential genotoxic effects of methanolic extracts of Euphorbia hirta which is commonly used in traditional medicine to treat a variety of diseased conditions including asthma, coughs, diarrhea and dysentery was investigated using Allium cepa assay. The extracts of 125, 250, 500 and 1,000 µg/mL were tested on root meristems of A. cepa. Ethylmethanesulfonate was used as positive control and distilled water was used as negative ...

  10. Neoplastic transformation of breast epithelial cells by genotoxic stress

    OpenAIRE

    Raman Venu; Winnard Paul T; Botlagunta Mahendran

    2010-01-01

    Abstract Background Exposure to genotoxic stresses such as radiation and tobacco smoke can cause increased cancer incidence rate as reflected in an in depth meta-analysis of data for women and breast cancer incidence. Published reports have indicated that exposures to low dose radiation and tobacco smoke are factors that contribute to the development of breast cancer. However, there is a scarcity of information on the combinatorial effects of low dose radiation and tobacco smoke on formation ...

  11. 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.

  12. Genotoxicity of organic extracts of house dust from Shanxi, China

    Energy Technology Data Exchange (ETDEWEB)

    Naufal, Z.; Zhou, G.D.; McDonald, T.; Li, Z.W.; Li, Z.; Donnelly, K.C. [Texas A& amp; M Health Science Center, College Station, TX (USA). School for Rural Public Health

    2007-07-01

    Indoor combustion of solid fuel such as coal may generate respirable particles containing polycyclic aromatic hydrocarbons (PAH) that may adhere to settled dust. Dust might therefore present a major source of PAH exposure in humans. This study evaluated the in vitro and in vivo genotoxicity of PAH mixtures extracted from house dust samples. Four dust samples (E1-4) were collected from houses in Shanxi, China, where coal is heavily used for heating and cooking. For comparison, a coal sample was also collected from one of the houses and included in the analyses. The samples were extracted with methylene chloride: acetone (95:5 v/v), dried, and redissolved in appropriate solvents for assessment in genotoxicity assays. Samples were evaluated for their ability to induce point mutations in bacteria and DNA adducts in vivo. DNA adduct levels were analyzed by nuclease P1-enhanced P-32-postlabeling. PAH were quantified using gas chromatography/mass spectrometry. Based on chemical analysis, sample E1 had the highest concentration by sampling area of benzo(a) pyrene (BaP) (181 {mu} g/m{sup 2}) and total PAH (10100 {mu} g/m{sup 2}). However, based on the microbial genotoxicity assay, sample E3, with the highest carcinogenic PAH/total PAH ratio (26%), produced the greatest number of revertants. In mice, administration of the extract of coal induced more adducts (9.81 adducts per 109 nucleotides) than dust extracts. The results of this study confirm the presence of genotoxic chemicals in residential dust. Inhalation of respirable particles containing similar mixtures of PAH represents a cancer risk for humans.

  13. COLONIC ADENOCARCINOMA WITH MALAKOPLAKIA OF COLON - A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Chitrawati Bal

    2015-09-01

    Full Text Available The gastrointestinal tract is the most common site for malakoplakia outside the urinary tract. A variety of conditions co - exists with malakoplakia including inflammatory bowel disease, systemic lupus erythematosus, immunodeficiency and tuberculosis. Rarely, it is associated with colonic ad enocarcinoma or adenomas. We report a case of malakoplakia in association with colonic adenocarcinoma.

  14. 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.

  15. 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.

  16. Genotoxic effects of sodium nitrate in onion roots

    Directory of Open Access Journals (Sweden)

    Maria-Mihaela ANTOFIE

    2013-11-01

    Full Text Available The scope of this paper is to assess cyto- and genotoxic effects of sodium nitrate on Allium cepa root tips by using different concentrations (i.e. 0,1%; 1% and 5% for treating uniform healthy onion bulbs for three different periods of time: 6, 24 and 72 hours. In the end of the experiment the harvested root tips were prepared according to Feulgen’s squash technique using Schiff reagent and the investigations were realized according to Allium test. The cytotoxic and genotoxic effects of nitrate were investigated by calculating the mitotic index and observing all chromosomes’ complement alterations during the mitosis. The phase rate of cells undergoing mitosis is also studied. For microscopy investigations a Novex Holland B microscope with digital camera included was used. The cytogenetic analysis of nitrate effects revealed a strong decrease in the mitotic index which is more intense with the concentration and time of exposure. Moreover, this effect is associated in case of the variant treated with 5% sodium nitrate acting for more than 24 hours, with the appearance of genotoxic effects such as chromosomal alterations, highly condensed chromatin expression easily identified during mitosis stages, sticky chromosomes and chromosomal bridges and laggards.

  17. 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

  18. 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.

  19. Genotoxicity of unmodified and organo-modified montmorillonite.

    Science.gov (United States)

    Sharma, Anoop Kumar; Schmidt, Bjørn; Frandsen, Henrik; Jacobsen, Nicklas Raun; Larsen, Erik Husfeldt; Binderup, Mona-Lise

    2010-07-19

    The natural clay mineral montmorillonite (Cloisite) Na+) and an organo-modified montmorillonite (Cloisite 30B) were investigated for genotoxic potential as crude suspensions and as suspensions filtrated through a 0.2-microm pore-size filter to remove particles above the nanometre range. Filtered and unfiltered water suspensions of both clays did not induce mutations in the Salmonella/microsome assay at concentrations up to 141microg/ml of the crude clay, using the tester strains TA98 and TA100. Filtered and unfiltered Cloisite) Na+ suspensions in culture medium did not induce DNA strand-breaks in Caco-2 cells after 24h of exposure, as tested in the alkaline comet assay. However, both the filtered and the unfiltered samples of Cloisite 30B induced DNA strand-breaks in a concentration-dependent manner and the two highest test concentrations produced statistically significantly different results from those seen with control samples (porgano-modified montmorillonite was caused by the organo-modifier. The detected organo-modifier mixture was synthesized and comet-assay results showed that the genotoxic potency of this synthesized organo-modifier was in the same order of magnitude at equimolar concentrations of organo-modifier in filtrated Cloisite) 30B suspensions, and could therefore at least partly explain the genotoxic effect of Cloisite) 30B.

  20. In vivo and in vitro genotoxicity studies of Semelil (ANGIPARSTM

    Directory of Open Access Journals (Sweden)

    Khorram Khorshid HR

    2008-04-01

    Full Text Available Semelil is a novel herbal-based compound formulated for treatment of bed sore and diabetic foot ulcer. The objective of the present preclinical study was to assess the mutagenicity and genotoxicity of Semelil in full compliance with the standard guidelines for testing chemicals. "nThe potential genotoxicity of Semelil, as part of the safety evaluation process was assessed in three different in vitro and in vivo tests, including bacterial reverse mutation (Ames test, mammalian bone marrow chromosomal aberration, and rodent dominant lethal assays. "nEffects of Semelil was clearly negative at different doses in the Ames test. No statistically significant differences were observed between the levels of chromosomal aberrations in bone marrow cells of mice from the experimental and control groups. The rate of post-implantation losses and thus, the number of lethal mutations in germ cells at different stages of spermatogenesis in male mice treated with a single dose of Semelil did not statistically exceed the control rate. While on the basis of these observations, Semelil can be considered genotoxically safe, further investigations using other bio-assays for mutagenicity studies are warranted.

  1. 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.

  2. 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.

  3. An Act of Colonization

    DEFF Research Database (Denmark)

    Rasmussen, Anders Bo

    When Gideon Welles, U.S. Secretary of the Navy, sat down to write his diary entry on September 26, 1862, his thoughts turned once more to colonization. President Lincoln was an ardent proponent of colonization, “the government-promoted settlement of black Americans in Africa or some other location......” and based on the recurring cabinet discussions, Welles understood that “Great Britain, Denmark and perhaps other powers would take them [the black population].” Since at least 1860, Denmark had encouraged the American government to send the “quite uncivilized (…) Africans liberated” from slave ships to St...... and the United States signed an act on July 19, 1862, wherein the U.S. Navy agreed to unload “all negroes, mulattoes, or persons of color, delivered from on board vessels seized in the prosecution of the slave trade.” Yet, despite the two countries’ mutual interests in employing “laborers of African Extraction...

  4. Malacoplaquia intestinal Colonic malakoplakia

    Directory of Open Access Journals (Sweden)

    Jacinto José Frem Aun

    1998-04-01

    Full Text Available Malacoplakia is a chronic granulomatous disease of unknown origin. However immunodeficiency states (immunossuppressive medication, old people, renal transplantation, leukaemia, diabetes mellitus, malnutrition and others have been associated with patients with malacoplakia. An infectious cause of malakoplakia is suggested by the finding of coliform bacteria in the phagolysosomes of macrophages. The histologic study is characterized by a infiltrate of large macrophages (Hansenmann cells with pathognomonic inclusions containing siderocalcific structures (Michaelis-Gutmann bodies. Most of the cases reported in literature, involve the genitourinary tract, but other structures can be affected (brain, bone, adrenal glands, lymph nodes, intestine, and others. A 66-year-old man whith a abdominal mass, went to our hospital with a colonic tumour diagnosis. The patient was submitted to a surgery, with resection of the rigth colon. The disease was invading a portion of the retroperitoneal tissue that was removed. The histopatologic study showed the pathognomonic sign of malakoplakia (Hansenmann cells and Michaelis-Gutmann bodies. Norfloxacin have been used to the complementar treatment with total cure of the patient.

  5. High throughput comet assay to study genotoxicity of nanomaterials

    Directory of Open Access Journals (Sweden)

    Naouale El Yamani

    2015-06-01

    Full Text Available The unique physicochemical properties of engineered nanomaterials (NMs have accelerated their use in diverse industrial and domestic products. Although their presence in consumer products represents a major concern for public health safety, their potential impact on human health is poorly understood. There is therefore an urgent need to clarify the toxic effects of NMs and to elucidate the mechanisms involved. In view of the large number of NMs currently being used, high throughput (HTP screening technologies are clearly needed for efficient assessment of toxicity. The comet assay is the most used method in nanogenotoxicity studies and has great potential for increasing throughput as it is fast, versatile and robust; simple technical modifications of the assay make it possible to test many compounds (NMs in a single experiment. The standard gel of 70-100 μL contains thousands of cells, of which only a tiny fraction are actually scored. Reducing the gel to a volume of 5 μL, with just a few hundred cells, allows twelve gels to be set on a standard slide, or 96 as a standard 8x12 array. For the 12 gel format, standard slides precoated with agarose are placed on a metal template and gels are set on the positions marked on the template. The HTP comet assay, incorporating digestion of DNA with formamidopyrimidine DNA glycosylase (FPG to detect oxidised purines, has recently been applied to study the potential induction of genotoxicity by NMs via reactive oxygen. In the NanoTEST project we investigated the genotoxic potential of several well-characterized metal and polymeric nanoparticles with the comet assay. All in vitro studies were harmonized; i.e. NMs were from the same batch, and identical dispersion protocols, exposure time, concentration range, culture conditions, and time-courses were used. As a kidney model, Cos-1 fibroblast-like kidney cells were treated with different concentrations of iron oxide NMs, and cells embedded in minigels (12

  6. Explant cultures of human colon

    DEFF Research Database (Denmark)

    Autrup, Herman; Barrett, L.A.; Jackson, F.E.

    1978-01-01

    Human colonic epithelium has been cultured as explants in a chemically defined medium for periods of 1 to 20 days. The viability of the explants was shown by the preservation of the ultrastructural features of the colonic epithelial cells and by active incorporation of radioactive precursors into...

  7. Get Tested for Colon Cancer: Here's How

    Science.gov (United States)

    ... Local Offices Close + - Text Size Get Tested for Colon Cancer [Video] This free video explains the most commonly ... re like most people, the thought of getting colon cancer or even going for a colon cancer test ...

  8. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... Search Category Cancer A-Z Colorectal Cancer Colon Cancer Videos Thanks to improvements in prevention, early detection, ... also personal stories from colon cancer survivors. Colon Cancer Prevention & Risk Reduction Play Play Colorectal Cancer: A ...

  9. A sucrose-rich diet induces mutations in the rat colon

    DEFF Research Database (Denmark)

    Dragsted, L.O.; Daneshvar, B.; Vogel, Ulla Birgitte

    2002-01-01

    A sucrose-rich diet has repeatedly been observed to have cocarcinogenic actions in the colon and liver of rats and to increase the number of aberrant crypt foci in rat colon. To investigate whether sucrose-rich diets might directly increase the genotoxic response in the rat colon or liver, we have...... added sucrose to the diet of Big Blue rats, a strain of Fischer rats carrying 40 copies of the lambda-phage on chromosome 4. Dietary sucrose was provided to the rats for 3 weeks at four dose levels including the background level in the purified diet [3.4% (control), 6.9%, 13.8%, or 34.5%] without...... or in blood plasma. We conclude that a sucrose-rich diet directly or indirectly increases the mutation frequency in rat colon in a dose-dependent manner and concomitantly decreases the level of background DNA adducts, without a direct effect on the expression of major DNA repair enzyme systems. We also...

  10. 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

  11. Genotoxicity of copper oxide nanoparticles with different surface chemistry on rat bone marrow mesenchymal stem cells

    DEFF Research Database (Denmark)

    Zhang, Wenjing; Jiang, Pengfei; Chen, Wei

    2016-01-01

    chemistry had influence on the toxicity to some extent too. The intracellular reactive oxygen species (ROS) level of MSCs was then quantified. Finally, the genotoxicity of the CuO NPs was studied by comet assay. The results suggest that the genotoxicity of CuO NPs was mainly dependent on NPs concentration...... impact on the differentiation potential of the MSCs....

  12. 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

  13. Genotoxicity testing using the Mutatox assay: evaluation of benzo[a]pyrene as a positive control

    NARCIS (Netherlands)

    Klamer, H.J.C.; Villerius, L.A.; Roelsma, J.; Maagd, de P.G.J.; Opperhuizen, A.

    1997-01-01

    In a study on bioassay-directed chemical factionation of sediment extracts, problems were encountered using benzo(a)pyrene (BaP) as a positive control in the Mutatox™ bacterial genotoxicity assay. Genotoxic responses of tests with this compound, prescribed by the Mutatox supplier, could only be meas

  14. The development of improved and new in vitro assays for detecting the genotoxic and non-genotoxic carcinogenic potential of chemicals in the discovery phase of drug development

    NARCIS (Netherlands)

    Westerink, W.M.A.

    2011-01-01

    In drug development, toxicity is an important factor for attrition, resulting in a failure rate of 30%-40%. Hepatotoxicity, nephrotoxicity, cardiovascular safety, reproduction toxicity, developmental toxicity (teratogenicity), genotoxicity and carcinogenicity are the main causes for attrition in saf

  15. Genotoxic and anti-genotoxic effects of esculin and its oligomer fractions against mitomycin C-induced DNA damages in mice.

    Science.gov (United States)

    Mokdad Bzeouich, Imen; Mustapha, Nadia; Maatouk, Mouna; Ghedira, Kamel; Ghoul, Mohamed; Chekir-Ghedira, Leila

    2016-12-01

    Mitomycin C is one of the most effective chemotherapeutic drugs against various solid tumors. However, despite its wide spectrum of clinical benefits, this agent is capable of inducing various types of genotoxicity. In this study, we investigated the effect of esculin and its oligomer fractions (E1, E2 and E3) against mitomycin C induced genotoxicity in liver and kidney cells isolated from Balb/C mice using the comet assay. Esculin and its oligomer fractions were not genotoxic at the tested doses (20 mg/kg and 40 mg/kg b.w). A significant decrease in DNA damages was observed, suggesting a protective role of esculin and its oligomer fractions against the genotoxicity induced by mitomycin C on liver and kidney cells. Moreover, esculin and its oligomer fractions did not induce an increase of malondialdehyde levels.

  16. Diverticulosis of colon: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Han, Chang Yul [Paik Hospital, Seoul (Korea, Republic of)

    1972-12-15

    The authors reports 2 cases of diverticulosis involving the sacending colon and cecum: one, 55 year old, 85 kg Korean male admitted to Paik Hospital because of abdominal palm, constipation and tenderness in the right lower abdomen. The other, 48 year old, 78 kg male visited to our hospital for the routine examination. According to late European and American statistics, the colonic diverticulosis was discovered in late middle life about 20%, however, the incidence of colonic diverticulosis is rare in Korea. This paper presents a brief review of literature on the etiology, incidence and symptom.

  17. Colonic lymphangiomatosis associated with anemia

    Institute of Scientific and Technical Information of China (English)

    Woo Chul Chung; Hye-Kang Kim; Jin Young Yoo; Jeong Rok Lee; Kang-Moon Lee; Chang Nyol Paik; U-Im Jang; Jin Mo Yang

    2008-01-01

    lymphangioma is an uncommon malformation of lymphatic system.Multiple colonic lymphangioma named as lymphangiomatosis is considered an extremely rare disease.Although lymphangioma is a benign tumor and most colonic lymphangiomas do not cause symptoms and do not require treatment,resection of lymphangioma is necessary in the presence of symptoms such as abdominal pain,bleeding,intussusceptions.We report a case of colonic lymphangiomatosis in a man who presented with abdominal discomfort and anemia,which was diagnosed and treated with endoscopic snare polyperctomy.

  18. 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.

  19. Screening potential genotoxic effect of aquatic plant extracts using the mussel micronucleus test

    Directory of Open Access Journals (Sweden)

    Bettina Eck-Varanka

    2016-01-01

    Full Text Available 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, and Oenanthe aquatica (L. Poir. (water dropwort, family Umbelliferae. Methods: For genotoxicity assessment, the mussel micronucleus test was applied. Micronucleus frequency was determined from the haemolymph of Unio 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.

  20. 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.

  1. Assessment of methyl methacrylate genotoxicity by the micronucleus test.

    Science.gov (United States)

    Araújo, Amarildo Mariano de; Alves, Guilherme Rodrigues; Avanço, Guilherme Trevisan; Parizi, José Luiz Santos; Nai, Gisele Alborghetti

    2013-01-01

    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.

  2. Genotoxic and antimicrobial studies of the leaves of Psidium guajava

    Directory of Open Access Journals (Sweden)

    Nwannemka Lauretta Ofodile

    2013-11-01

    Full Text Available Background: The guava, Psidium guajava is one of the most gregarious of fruit trees, of the Myrtaceae family. The leaf of P. guajava is a common herb used in the treatment of diarrhea in Nigeria and this has generated special interest in the probable antimicrobial and genotoxic effects of the leaf. However the mode of action of the leaf extracts has not been reported, hence the genotoxicity study. Materials and Methods: Antimicrobial activity of the aqueous and ethanolic extracts of the leaves of Psidium guajava on Aspergillus fumigatus, Candida albicans, Salmonella spp., and Staphylococcus aureus were investigated using agar-well method and also subjected to phytochemical screening and Gas chromatography-Mass spectroscopy analysis. General toxicity and genotoxic effects of the aqueous leaf extracts (0.01 g/mL, 0.03 g/mL, 0.06 g/mL and 0.08 g/mL of P. guajava on Allium cepa root tips were also investigated using aceto-orcein squash technique. Results: Results showed that both aqueous and ethanolic extracts of guava leaf inhibited the growth of the bacteria and fungi tested. The ethanolic extract showed stronger inhibition than the aqueous extract against the organisms. A total of forty one compounds were identified in guava leaves using GC-MS analysis and these substances were found to be essential oils. The cytological effects at low concentration included mainly c-mitosis, vagrant chromosomes, chromosome bridges, and binucleate cells with EC50 of 0.02 g/mL. Conclusion: The antimicrobial activity of the essential oils from the extracts of leaves of P. guajava could be partly due to alterations associated with the cell division as deduced from the results.

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

    Directory of Open Access Journals (Sweden)

    Amaya Azqueta

    2015-06-01

    Full Text Available In the last two decades the production and use of nanomaterials (NMs has impressively increased. Their small size, given a mass equal to that of the corresponding bulk material, implies an increase in the surface area and consequently in the number of atoms that can be reactive. They possess different physical, chemical and biological properties compared to bulk materials of the same composition, which makes them very interesting and valuable for many different applications in technology, energy, construction, electronics, agriculture, optics, paints, textiles, food, cosmetics, medicine... Toxicological assessment of NMs is crucial; the same properties that make them interesting also make them potentially harmful for health and the environment. However, the term NM covers many different kinds of particle , and so there is no simple, standard approach to assessing their toxicity. NMs can enter the cell, interact with cell components and even penetrate the nucleus and interfere with the genetic material. Among the different branches of toxicology, genotoxicity is a main area of concern since it is closely related with the carcinogenic potential of compounds. The Organisation for Economic Co-operation and Development (OECD has published internationally agreed in vitro and in vivo validated test methods to evaluate different genotoxic endpoints of chemicals, including chromosome and gene mutations, and DNA breaks. However not all the assays are suitable to study the genotoxic potential of NMs as has been shown by the OECD Working Party on Manufactured Nanomaterials (WPMN. Moreover, alterations to DNA bases, which are precursors to mutations and of great importance in elucidating the mechanism of action of NMs, are not covered by the OECD guidelines. The in vivo standard comet assay (which measures DNA breaks and alkali-labile sites was included in the OECD assays battery in September 2014 while the in vitro standard comet assay is currently under

  4. 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...

  5. Cholesterol metabolism and colon cancer.

    Science.gov (United States)

    Broitman, S A; Cerda, S; Wilkinson, J

    1993-01-01

    While epidemiologic and concordant experimental data indicate a direct relationship between dietary fat (and presumably caloric) intake and the development of colon cancer, the effect of dietary cholesterol on this disease is still not clear. However, there appears to be a developing literature concerning an inverse relationship between serum and plasma cholesterol levels, and the risk for colon cancer. Findings that low serum cholesterol levels are apparent as early as ten years prior to the detection of colon cancer implies that sub clinical disease is probably not involved initially in this process. The possibility of low serum cholesterol as a bio-marker was considered in epidemiologic studies which focused upon obese men with lower than normal serum cholesterol levels who were found to be at increased risk to colon cancer. While the relationship between low serum cholesterol and colonic or intestinal cholesterol metabolism is presently not understood, current genetic studies provide a promising though as yet unexplored potential association. Alterations which occur during the developmental progression of colonic cancer include changes in chromosome 5, which also carries two genes vital to the biosynthesis and regulation of systemic and cellular cholesterol metabolism, 3-hydroxy-3-methylglutaryl coenzyme A synthase, and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA R). Regulation of cholesterol metabolism in intestinal cells in vivo and in vitro varies from that seen in normal fibroblasts or hepatocytes in terms of exogenous sources of cholesterol and how these sources regulate internal synthesis. Colonic cancer cells have been used to assess small bowel enterocyte cholesterol metabolism, which has been possible because of their ability to differentiate in culture, however information regarding true colonic enterocyte cholesterol metabolism is relatively scarce. Colonic cancer cells have been shown to possess a diminished or nonexistent ability to use

  6. Spontaneous Perforation of Rectosigmoid Colon

    Directory of Open Access Journals (Sweden)

    Farhad Haj Sheikholeslami

    2010-12-01

    Full Text Available Spontaneous perforation of the sigmoid colon or rectom is definedas a sudden perforation of the colon in the absence of diseasessuch as tumors, diverticulosis or external injury. It is avery rare finding, and if neglected, results in severe peritonitisand high mortality. The causes of this rare condition are numerous,and in this case it might be due to the chronic constipationinduced by an anticholinergic antipsychotic.Iran J Med Sci 2010; 35(4: 339-341.

  7. [Lactobacilli and colon carcinoma--A review].

    Science.gov (United States)

    Wang, Shumei; Zhang, Lanwei; Shan, Yujuan

    2015-06-04

    Epidemiological studies showed that incidence of colon carcinoma is increased in the world. There are many difficulties to inhibit colon carcinoma because the causes of inducing colon carcinoma were various and interactive each other. Previous evidence supported the balance of the colonic microflora was critical in inhibiting colon carcinoma and the protection by colonic microflora could be improved by ingesting lactobacilli. Therefore, the biological functions and anticancer effects of lactobacilli attract attention of researchers. In this review we discussed the causes of colon carcinoma; the anticancer mechanisms of lactobacilli on the basis of our own studies. Eventually, we summarized the effects of anticancer of different components and metabolic products extracted from lactobacilli.

  8. 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.

  9. A possible role for chromium(III) in genotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Snow, E.T. (New York Univ. Medical Center, Tuxedo (United States))

    1991-05-01

    Chromium is found in the environment in two major forms: reduced Cr{sup III} and Cr{sup VI}, or chromate. Chromate, the most biologically active species, is readily taken up by living cells and reduced intracellularly, via reactive intermediates, to stable Cr{sup III} species. Cr{sup III}, the most abundant form of chromium in the environment, does not readily cross cell membranes and is relatively inactive in vivo. However, intracellular Cr{sup III} can react slowly with both nucleic acids and proteins and can be genotoxic. The authors have investigated the genotoxicity of Cr{sup III} in vitro using a DNA replication assay and in vivo by CaCl{sub 2}-mediated transfection of chromium-treated DNA into Escherichia coli. These results suggest that Cr{sup III} alters the interaction between the DNA template and the polymerase such that the binding strength of the DNA polymerase is increased and the fidelity of DNA replication is decreased. These interactions may contribute to the mutagenicity of chromium ions in vivo and suggest that Cr{sup III} can contribute to chromium-mediated carcinogenesis.

  10. 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.

  11. 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.

  12. 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.

  13. Pb low doses induced genotoxicity in Lactuca sativa plants.

    Science.gov (United States)

    Silva, S; Silva, P; Oliveira, H; Gaivão, I; Matos, M; Pinto-Carnide, O; Santos, C

    2017-03-01

    Soil and water contamination by lead (Pb) remains a topic of great concern, particularly regarding crop production. The admissible Pb values in irrigation water in several countries range from ≈0.1 to ≈5 mg L(-1). In order to evaluate putative effects of Pb within legal doses on crops growth, we exposed Lactuca sativa seeds and seedlings to increasing doses of Pb(NO3)2 up to 20 mg L(-1). The OECD parameter seed germination and seedling/plant growth were not affected by any of the Pb-concentrations used. However, for doses higher than 5 mg L(-1) significant DNA damage was detected: Comet assay detected DNA fragmentation at ≥ 5 mg L(-1) and presence of micronuclei (MN) were detected for 20 mg L(-1). Also, cell cycle impairment was observed for doses as low as 0.05 mg L(-1) and 0.5 mg L(-1) (mostly G2 arrest). Our data show that for the low doses of Pb used, the OECD endpoints were not able to detect toxicity, while more sensitive endpoints (related with DNA damage and mitotic/interphase disorders) identified genotoxic and cytostatic effects. Furthermore, the nature of the genotoxic effect was dependent on the concentration. Finally, we recommend that MN test and the comet assay should be included as sensitive endpoints in (eco)toxicological assays.

  14. 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.

  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. 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.

  17. 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.

  18. 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.

  19. Studies on Potential Mutagenic and Genotoxic Activity of Setarud

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    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.

  20. 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.

  1. 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).

  2. 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.

  3. 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).

  4. Optimization of low energy sonication treatment for granular activated carbon colonizing biomass assessment.

    Science.gov (United States)

    Saccani, G; Bernasconi, M; Antonelli, M

    2014-01-01

    This study is aimed at optimizing a low energy sonication (LES) treatment for granular activated carbon (GAC)-colonizing biomass detachment and determination, evaluating detachment efficiency and the effects of ultrasound exposure on bacterial cell viability. GAC samples were collected from two filters fed with groundwater. Conventional heterotrophic plate count (HPC) and fluorescence microscopy with a double staining method were used to evaluate cell viability, comparing two LES procedures, without and with periodical bulk substitution. A 20 min LES treatment, with bulk substitution after cycles of 5 min as maximum treatment time, allowed to recover 87%/100% of attached biomass, protecting detached bacteria from ultrasound damaging effects. Observed viable cell inactivation rate was 6.5/7.9% cell/min, with membrane-compromised cell damage appearing to be even higher (11.5%/13.1% cell/min). Assessing bacterial detachment and damaging ultrasound effects, fluorescence microscopy turned out to be more sensitive compared to conventional HPC. The optimized method revealed a GAC-colonizing biomass of 9.9 x 10(7) cell/gGAC for plant 1 and 8.8 x 10(7) cell/gGAC for plant 2, 2 log lower than reported in literature. The difference between the two GAC-colonizing biomasses is higher in terms of viable cells (46.3% of total cells in plant 1 GAC-colonizing biomass compared to the 33.3% in plant 2). Studying influent water contamination through multivariate statistical analyses, apossible combined toxic and genotoxic effect of chromium VI and trichloroethylene was suggested as a reason for the lower viable cell fraction observed in plant 2 GAC-colonizing population.

  5. 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.

  6. Persistence of anticancer activity in berry extracts after simulated gastrointestinal digestion and colonic fermentation.

    Directory of Open Access Journals (Sweden)

    Emma M Brown

    Full Text Available Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0-50 µg/ml gallic acid equivalents, the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer.

  7. Additional survey on genotoxicity of natural anthraquinones in the hepatocyte primary culture/DNA repair assay.

    Science.gov (United States)

    Mori, H; Yoshimi, N; Iwata, H; Tanaka, T; Kawai, K; Sankawa, U

    1988-08-01

    Genotoxicity of fungal anthraquinones of islandicin, iridoskyrin and (-) rubroskyrin, and a colorant of insect origin, cochineal and its component, carminic acid, an anthraquinone, was examined in the hepatocyte primary culture/DNA repair test. The results were compared with that of versicolorin A, an anthraquinone with bisfuran ring, which had been proved to be genotoxic on this assay. All of these anthraquinones, differently from versicolorin A did not show clear response of DNA repair. The results suggest that these agents are not genotoxic carcinogens.

  8. 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.

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

    Science.gov (United States)

    Costa, Solange; Coelho, Patrícia; Costa, Carla; Silva, Susana; Mayan, Olga; Santos, Luís Silva; Gaspar, Jorge; Teixeira, João Paulo

    2008-10-30

    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+/-0.08ppm (0.04-1.58ppm). 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 found between FA

  11. RARE CASE OF COLONIC METASTASIS

    Directory of Open Access Journals (Sweden)

    Vinod Kumar

    2015-04-01

    Full Text Available Colon cancer is the second most common type of cancer in females and the third in males worldwide. The most common sites of colon cancer metastasis are the regional lymph nodes, liver, lung, bone and brain. In this case report, an extremely rare case of colon adenocarcinoma with metastasis to the philtrum with extensive peritoneal and bowel involvement is presented. A 44 year old male presented with a change in bowel habits, melena and weight loss . Diagnosed to have carcinoma rectum underwent Abdominoperenial resection (APR two y ears back. Biopsies were consistent with the diagnosis of invasive moderately differentiated adenocarcinoma. Now presented with swelling over philtrum . Fine needle aspiration (FNAC was done suggestive of adenocarcinoma. This case presented for its uncommon presentation.

  12. 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

    , expression was unaffected by DEP or sucrose feeding. Among biomarkers of oxidative stress, including vitamin C, malondialdehyde and protein oxidations (gamma-glutamyl semialdehyde and 2-amino adipic semialdehyde) in plasma and liver, only malondialdehyde was increased in plasma by sucrose/DEP feeding...

  13. Biomonitoring of genotoxic exposure among stainless steel welders

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Boisen, T; Christensen, J M

    1992-01-01

    A biosurvey in the Danish metal industry measured the genotoxic exposure from stainless steel welding. The study comprised measurements of chromosomal aberrations (CA), sister-chromatid exchanges (SCE), unscheduled DNA synthesis (UDS) in peripheral lymphocytes and serum immunoglobulin G....... A higher frequency of chromosomal aberrations, classified as translocations, double minutes, exchanges and rings, was observed in stainless steel welders than in non-welders. SCE was lower in welders working with both MMA and TIG welding than in reference persons. N-Acetoxy-N-acetylaminofluorene (NA...... lymphocytes in exposed persons compared with non-exposed are suggested. MMA welding gave the highest exposure to chromium, an increased number of chromosomal aberrations and a decrease in SCE when compared with TIG welding. Consequently improvements in the occupational practice of stainless steel welding...

  14. The potential for new methods to assess human reproductive genotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Mendelsohn, M.L.

    1987-09-01

    The immediate prospects are not good for practical methods for measuring the human heritable mutation rate. The methods discussed here range from speculative to impractical, and at best are sensitive enough only for large numbers of subjects. Given the rapid development of DNA methods and the current status of two-dimensional gel electrophoresis, there is some hope that the intermediate prospects may be better. In contrast, the prospects for useful cellular-based male germinal methods seem more promising and immediate. Effective specific locus methods for sperm are already conceivable and may be practical in a few years. Obviously such methods will not predict heritable effects definitively, but they will provide direct information on reproductive genotoxicity and should contribute significantly to many current medical and environmental situations where genetic damage is suspected. 22 refs.

  15. Neurological manifestation of colonic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Uzair Chaudhary

    2012-04-01

    Full Text Available Paraneoplastic neurologic disorders are extremely rare in cancer patients and are most commonly associated with certain tumors, such as ovarian cancer, small cell lung cancer, and breast cancer. We report here a paraneoplastic neurological syndrome in a 53-year-old man with colonic adenocarcinoma with a solitary liver metastasis. His paraneoplastic syndrome was successfully treated by methylprednisolone and primary oncologic therapies including neoadjuvant chemotherapy and definitive surgery. This is also the first documented case of simultaneous manifestation of a sensory neuropathy and limbic encephalitis with colon cancer.

  16. Medullary carcinoma of the colon

    DEFF Research Database (Denmark)

    Fiehn, Anne-Marie Kanstrup; Grauslund, Morten; Glenthøj, Anders

    2015-01-01

    Medullary carcinoma of the colon is a rare variant of colorectal cancer claimed to have a more favorable prognosis than conventional adenocarcinomas. The histopathologic appearance may be difficult to distinguish from poorly differentiated adenocarcinoma. The study aimed to evaluate the diagnostic...... differences in CK20 (p = 0.005) expression and in the rate of BRAF mutations (p = 0.0035). In conclusion, medullary carcinomas of the colon are difficult to discriminate from poorly differentiated adenocarcinoma even with the help of immunohistochemical and molecular analyses. This raises the question whether...

  17. Colon,rectum and anus

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008303 MicroRNA expression profiling in hydrox-ycamptothecin-resistant human colon cancer cell line by microarray.TONG Jinlu(童锦禄), et al. Dept Gastroenterol, Renji Hosp, Med Sch, Shanghai Jiaotong Univ, Shanghai Instit Dig Dis, Shanghai 200001. Chin J Dig 2008;28(4):246-249.Objective To explore the role of a novel regulatory molecule-microRNA in the hydroxycamptothecin-resistant human colon cancer cell line SW1116/HCPTin order to provide a new reversal target for multidrug resistance.

  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 effect of Phenanthrene on Chironomus sancticaroli (Diptera: Chironomidae

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    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. Comet Assay on Daphnia magna in eco-genotoxicity testing.

    Science.gov (United States)

    Pellegri, Valerio; Gorbi, Gessica; Buschini, Annamaria

    2014-10-01

    Detection of potentially hazardous compounds in water bodies is a priority in environmental risk assessment. For the evaluation and monitoring of water quality, a series of methodologies may be applied. Among them, the worldwide used toxicity tests with organisms of the genus Daphnia is one of the most powerful. In recent years, some attempts were made to utilize Daphnia magna in genotoxicity testing as many of the new environmental contaminants are described as DNA-damaging agents in aquatic organisms. The aim of this research was to develop a highly standardized protocol of the Comet Assay adapted for D. magna, especially regarding the isolation of cells derived from the same tissue (haemolymph) from newborn organisms exposed in vivo. Several methods for haemolymph extraction and different Comet Assay parameters were compared. Electrophoretic conditions were adapted in order to obtain minimum DNA migration in cells derived from untreated organisms and, at the same time, maximum sensitivity in specimens treated with known genotoxicants (CdCl2 and H2O2). Additional tests were performed to investigate if life-history traits of the cladoceran (such as the age of adult organisms that provide newborns, the clutch size of origin, the number of generations reared in standard conditions) and the water composition as well, might influence the response of the assay. This study confirms the potential application of the Comet Assay in D. magna for assessing genotoxic loads in aqueous solution. The newly developed protocol could integrate the acute toxicity bioassay, thus expanding the possibility of using this model species in freshwater monitoring (waters, sediment and soil elutriates) and is in line with the spirit of the EU Water Framework Directive in reducing the number of bioassays that involve medium-sized species.

  1. COMPARATIVE GENOTOXIC RESPONSES TO ARSENITE IN GUINEA PIG, MOUSE, RAT AND HUMAN LYMPHOCYTES

    Science.gov (United States)

    Comparative genotoxic responses to arsenite in guinea pig, mouse, rat and human lymphocytes.Inorganic arsenic is a known human carcinogen causing skin, lung, and bladder cancer following chronic exposures. Yet, long-term laboratory animal carcinogenicity studies have ...

  2. Detection of genotoxic, cytotoxic, and protective activities of Eugenia dysenterica DC. (Myrtaceae) in mice.

    Science.gov (United States)

    Vieira, Pabline Marinho; Veronezi, Eduardo; Silva, Carolina R; Chen-Chen, Lee

    2012-06-01

    Eugenia dysenterica DC. (Myrtaceae), popularly known in Brazil as cagaiteira, is a widespread plant species in the Brazilian Cerrado. In folk medicine, the leaves of this plant are used to treat diarrhea and dysentery. The fruits are used for fresh consumption and industrial purposes. Because of the use of this plant as a therapeutic resource and food, the present study evaluated the genotoxic, cytotoxic, antigenotoxic, and anticytotoxic effects of the lyophilized ethanolic leaf extract of E. dysenterica using the mouse bone marrow micronucleus test. The genotoxicity and antigenotoxicity of this extract were evaluated using the frequency of micronucleated polychromatic erythrocytes, and the cytotoxicity and anticytotoxicity were assessed by the polychromatic and normochromatic erythrocyte ratio. According to our results, the lyophilized ethanolic leaf extract of E. dysenterica exhibited genotoxic and cytotoxic effects at the higher doses and protection against cyclophosphamide-induced genotoxic and cytotoxic actions at all doses tested.

  3. A compilation of genotoxicity and carcinogenicity data on aromatic aminosulphonic acids.

    Science.gov (United States)

    Jung, R; Steinle, D; Anliker, R

    1992-07-01

    A review is presented to evaluate existing information on genotoxicity and carcinogenicity testing of various aromatic aminosulphonic acids (AASAs). A great variety of water-soluble azo dyes can form aromatic phenyl- or naphthyl-aminosulphonic acids by chemical and enzymatic reduction. AASAs are also used as intermediates in the synthesis of azo dyes and azo pigments and can arise as contaminants in the final products. Comparisons have been made with the data available on the corresponding unsulphonated analogues, some of which are known to be genotoxic and/or carcinogenic. The vast majority of the AASAs were conclusively non-mutagenic in the Ames test. In most cases the absence of genotoxicity was also demonstrated with a variety of other test systems in vitro and in vivo. It is concluded that AASAs, in contrast with some of their unsulphonated analogues, generally have no or very low genotoxic and tumorigenic potential.

  4. The cytotoxicity and genotoxicity of soluble and particulate cobalt in human lung epithelial cells.

    Science.gov (United States)

    Xie, Hong; Smith, Leah J; Holmes, Amie L; Zheng, Tongzhang; Pierce Wise, John

    2016-05-01

    Cobalt is a toxic metal used in various industrial applications leading to adverse lung effects by inhalation. Cobalt is considered a possible human carcinogen with the lung being a primary target. However, few studies have considered cobalt-induced toxicity in human lung cells, especially normal lung epithelial cells. Therefore, in this study, we sought to determine the cytotoxicity and genotoxicity of particulate and soluble cobalt in normal primary human lung epithelial cells. Cobalt oxide and cobalt chloride were used as representative particulate and soluble cobalt compounds, respectively. Exposure to both particulate and soluble cobalt induced a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ion levels. Based on intracellular cobalt ion levels, we found that soluble and particulate cobalt induced similar cytotoxicity while soluble cobalt was more genotoxic than particulate cobalt. These data indicate that cobalt compounds are cytotoxic and genotoxic to human lung epithelial cells.

  5. 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.

  6. The Genotoxicity of Titanium Dioxide and Cerium Dioxide Nanoparticles in Human Respiratory Epithelial Cells

    Science.gov (United States)

    Due to the exponential growth of the nanomaterial industry, risk assessment of human exposure to nanomaterials in consumer products is of paramount importance. The genotoxicity of nanomaterials is an important aspect of hazard identification and regulatory guidance. However, this...

  7. Genotoxic Effects of Titanium Dioxide and Cerium Dioxide Nanoparticles in Human Respiratory Epithelial Cells

    Science.gov (United States)

    The nanomaterial industry has recently seen rapid growth, therefore, the risk assessment of human exposure to nanomaterials in consumer products is of paramount importance. The genotoxicity of nanomaterials is a fundamental aspect of hazard identification and regulatory guidance....

  8. METABOLISM, MICROFLORA EFFECTS, AND GENOTOXICITY IN HALOACETIC ACID-TREATED CULTURES OF RAT CECAL MICROBIOTA

    Science.gov (United States)

    Haloacetic acids are by-products of drinking water disinfection. Several compounds in this class are genotoxic and have been identified as rodent hepatocarcinogens. Enzymes produced by the normal intestinal bacteria can transform some promutagens and procarcinogens to their bio...

  9. Measurement of DNA strand breaks as a biomarker of genotoxic pollutants

    Digital Repository Service at National Institute of Oceanography (India)

    Sarkar, A.; Patil, S.S.; Holkar, P.K.R.

    This paper deals with the development of a molecular biomarker technique by measurement of DNA integrity in marine organisms for biomonitoring of pollution due to genotoxic compounds. The marine environment is continuously being polluted...

  10. KEYNOTE LECTURES-KL1 New development in risk assessment of genotoxic carcinogens in foods

    Institute of Scientific and Technical Information of China (English)

    CHEN Jun-Shi

    2006-01-01

    @@ The no-observed-effect level (NOEL) in a study of carcinogenicity for compounds that are both genotoxic and carcinogenic represents the limit of detection in that bioassay, rather than an estimate of a possible threshold. Therefore, for those genotoxic and carcinogenic contaminants (e.g. acrylamides, PAHs, etc.) in foods it is not possible to develop health-based guidance values (e.g. ADI or PTWI) using the traditional NOEL and safety/uncertainty factors.

  11. Vitamin C conjugates of genotoxic lipid peroxidation products: Structural characterization and detection in human plasma

    OpenAIRE

    Sowell, John; Frei, Balz; Stevens, Jan F.

    2004-01-01

    α,β-Unsaturated aldehydes such as 4-hydroxy-2-nonenal (HNE) and other electrophilic lipid peroxidation (LPO) products may contribute to the pathogenesis of cancer, cardiovascular diseases, and other age-related diseases by cytotoxic, genotoxic, and proinflammatory mechanisms. The notion that vitamin C (ascorbic acid) acts as a biological antioxidant has been challenged recently by an in vitro study showing that ascorbic acid promotes, rather than inhibits, the formation of genotoxic LPO produ...

  12. Characterization of Cr(V)-induced genotoxicity using CdTe nanocrystals as fluorescent probes.

    Science.gov (United States)

    Zhang, Wen-Hao; Sui, Chao-Xia; Wang, Xie; Yin, Gong-Ju; Liu, Ying-Fan; Zhang, Ding

    2014-12-21

    CdTe nanocrystals capped by cysteamine were synthesized to study Cr(V)-induced genotoxicity. On the surface of TiO2 thin films, the stepwise process of DNA breakage induced by Cr(V)-GSH complexes was vividly observed by using CdTe-DNA self-assembled fluorescent probes; in acetate buffer solution, an analytical method was developed to detect Cr(V)-induced genotoxicity with CdTe fluorescent probes.

  13. Genotoxic Pyrrolizidine Alkaloids — Mechanisms Leading to DNA Adduct Formation and Tumorigenicity

    OpenAIRE

    2002-01-01

    Abstract: Plants that contain pyrrolizidine alkaloids are widely distributed in the world. Although pyrrolizidine alkaloids have been shown to be genotoxic and tumorigenic in experimental animals, the mechanisms of actions have not been fully understood. The results of our recent mechanistic studies suggest that pyrrolizidine alkaloids induce tumors via a genotoxic mechanism mediated by 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5Hpyrrolizine (DHP)-derived DNA adduct formation. This mechanism may ...

  14. The use of ex vivo human skin tissue for genotoxicity testing

    Energy Technology Data Exchange (ETDEWEB)

    Reus, Astrid A.; Usta, Mustafa [TNO Triskelion BV, Utrechtseweg 48, 3704 HE, Zeist (Netherlands); Krul, Cyrille A.M., E-mail: cyrille.krul@tno.nl [TNO, Utrechtseweg 48, 3704 HE Zeist (Netherlands)

    2012-06-01

    As a result of the chemical legislation concerning the registration, evaluation, authorization and restriction of chemicals (REACH), and the Seventh Amendment to the Cosmetics Directive, which prohibits animal testing in Europe for cosmetics, alternative methods for safety evaluation of chemicals are urgently needed. Current in vitro genotoxicity assays are not sufficiently predictive for the in vivo situation, resulting in an unacceptably high number of misleading positives. For many chemicals and ingredients of personal care products the skin is the first site of contact, but there are no in vitro genotoxicity assays available in the skin for additional evaluation of positive or equivocal responses observed in regulatory in vitro genotoxicity assays. In the present study ex vivo human skin tissue obtained from surgery was used for genotoxicity evaluation of chemicals by using the comet assay. Fresh ex vivo human skin tissue was cultured in an air–liquid interface and topically exposed to 20 chemicals, including true positive, misleading positive and true negative genotoxins. Based on the results obtained in the present study, the sensitivity, specificity and accuracy of the ex vivo skin comet assay to predict in vivo genotoxicity were 89%, 90% and 89%, respectively. Donor and experimental variability were mainly reflected in the magnitude of the response and not the difference between the presence and absence of a genotoxic response. The present study indicates that human skin obtained from surgery is a promising and robust model for safety evaluation of chemicals that are in direct contact with the skin. -- Highlights: ► We use human skin obtained from surgery for genotoxicity evaluation of chemicals. ► We use the comet assay as parameter for genotoxicity in ex vivo human skin. ► Sensitivity, specificity and accuracy to predict in vivo genotoxins are determined. ► Sensitivity, specificity and accuracy are 89%, 90% and 90%, respectively. ► The method

  15. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... personal stories from colon cancer survivors. Colon Cancer Prevention & Risk Reduction Play Play Colorectal Cancer: A Resource ... Cancer About Colorectal Cancer Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment ...

  16. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... factors, screening tests, and treatments. There are also personal stories from colon cancer survivors. Colon Cancer Prevention & ... Cancer: Don't Ignore Your Symptoms Play Play Personal Story: Lex Gilbert Play Play Personal Story: Karen ...

  17. Get Tested for Colon Cancer: Here's How

    Medline Plus

    Full Text Available ... Contrast Barium Enema(DCBE) Play Play Colon Cancer Treatments Play Play Colon Cancer Surgery: What You Need ... Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To Top Imagine a world ...

  18. Treatment Options (by Stage) for Colon Cancer

    Science.gov (United States)

    ... Colorectal Cancer Colorectal Cancer Screening Research Colon Cancer Treatment (PDQ®)–Patient Version General Information About Colon Cancer ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  19. Breast and Colon Cancer Family Registries

    Science.gov (United States)

    The Breast Cancer Family Registry and the Colon Cancer Family Registry were established by the National Cancer Institute as a resource for investigators to use in conducting studies on the genetics and molecular epidemiology of breast and colon cancer.

  20. High prevalence of mucosa-associated E. coli producing cyclomodulin and genotoxin in colon cancer.

    Directory of Open Access Journals (Sweden)

    Emmanuel Buc

    Full Text Available Some Escherichia coli strains produce toxins designated cyclomodulins (CMs which interfere with the eukaryotic cell cycle of host cells, suggesting a possible link between these bacteria and cancers. There are relatively few data available concerning the colonization of colon tumors by cyclomodulin- and genotoxic-producing E. coli. We did a qualitative and phylogenetic analysis of mucosa-associated E. coli harboring cyclomodulin-encoding genes from 38 patients with colorectal cancer (CRC and 31 with diverticulosis. The functionality of these genes was investigated on cell cultures and the genotoxic activity of strains devoid of known CM-encoding gene was investigated. Results showed a higher prevalence of B2 phylogroup E. coli harboring the colibatin-producing genes in biopsies of patients with CRC (55.3% than in those of patients with diverticulosis (19.3%, (p<0.01. Likewise, a higher prevalence of B2 E. coli harboring the CNF1-encoding genes in biopsies of patients with CRC (39.5% than in those of patients with diverticulosis (12.9%, (p = 0.01. Functional analysis revealed that the majority of these genes were functional. Analysis of the ability of E. coli to adhere to intestinal epithelial cells Int-407 indicated that highly adherent E. coli strains mostly belonged to A and D phylogroups, whatever the origin of the strains (CRC or diverticulosis, and that most E. coli strains belonging to B2 phylogroup displayed very low levels of adhesion. In addition, 27.6% (n = 21/76 E. coli strains devoid of known cyclomodulin-encoding genes induced DNA damage in vitro, as assessed by the comet assay. In contrast to cyclomodulin-producing E. coli, these strains mainly belonged to A or D E. coli phylogroups, and exhibited a non significant difference in the distribution of CRC and diverticulosis specimens (22% versus 32.5%, p = 0.91. In conclusion, cyclomodulin-producing E. coli belonging mostly to B2 phylogroup colonize the colonic mucosa of

  1. Further investigations into the genotoxicity of quinoxaline-di-N-oxides and their primary metabolites.

    Science.gov (United States)

    Liu, Qianying; Zhang, Jianwu; Luo, Xun; Ihsan, Awais; Liu, Xianglian; Dai, Menghong; Cheng, Guyue; Hao, Haihong; Wang, Xu; Yuan, Zonghui

    2016-07-01

    Quinoxaline-di-N-oxides (QdNOs) are potential antibacterial agents with a wide range of biological properties. Quinocetone (QCT), carbadox (CBX), olaquindox (OLA), mequindox (MEQ) and cyadox (CYA) are classical QdNOs. Though the genotoxicity of parent drugs has been evaluated, the genotoxicity of their primary N → O reduced metabolites remains unclear. In the present study, a battery of four different short-term tests, mouse lymphoma assay (MLA), Ames test, chromosomal aberration assay in vitro and bone marrow erythrocyte micronucleus assay in vivo was carried out to investigate the genotoxicity of the six primary N → O reduced metabolites. Additionally, the genotoxicity of five parent drugs was evaluated by the MLA. Strong genotoxicity of N1-MEQ, B-MEQ and B-CBX was found in three of the assays but not in the Ames assay, and the rank order was N1-MEQ>B-MEQ>B-CBX that is consistent with prototype QdNOs. Negative results for the five QdNOs were noted in the MLA. We present for the first time a comparison of the genotoxicity of primary N → O reduced metabolites, and evaluate the ability of five QdNOs to cause mutations in the MLA. The present study demonstrates that metabolites are involved in genetic toxicity mediated by QdNOs, and improve the prudent use of QdNOs for public health.

  2. The in vitro genotoxic effect of Tucuma (Astrocaryum aculeatum), an Amazonian fruit rich in carotenoids.

    Science.gov (United States)

    de Souza Filho, Olmiro Cezimbra; Sagrillo, Michele Rorato; Garcia, Luiz Filipe Machado; Machado, Alencar Kolinski; Cadoná, Francine; Ribeiro, Euler Esteves; Duarte, Marta Maria Medeiros Frescura; Morel, Ademir Farias; da Cruz, Ivana Beatrice Mânica

    2013-11-01

    Tucuma (Astrocaryum aculeatum) is an Amazonian fruit that presents high levels of carotenoids and other bioactive compounds such as quercetin. The extracts of tucuma peel and pulp present strong antioxidant activity which illustrate an elevated concentration that causes cytotoxic effects in human peripheral blood mononuclear cells (PBMCs). This study performed additional investigations to analyze the potential genotoxic effects of the tucuma extracts on PBMCs. The genotoxicity was evaluated by DNA fragmentation, Comet assay, and chromosomal instability G-band assays. The acute tucuma extract treatment showed genoprotective effects against DNA denaturation when compared with untreated PBMC cells. However, in the experiments with 24 and 72 h treatments to tucuma treatments, we observed low genotoxicity through a concentration of 100 μg/mL, some genotoxic effects related to intermediary concentrations (100-500 μg/mL), and more pronounced genotoxic effects on higher tucuma extract concentrations. After 24 h of treatment, the reactive oxygen species were similar among treatments and PBMC control groups. However, the caspase-1 activity related to the apoptosis and pyroptosis process increased significantly in higher tucuma concentrations. In summary, tucuma extracts, despite their higher antioxidant content and antioxidant activity, would present PBMCs genotoxic effects that are dependent on concentration and time exposition. These results need to be considered in future in vitro and in vivo studies of tucuma effects.

  3. Colon,rectum and anus

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010344 Serotonin transporter expression in rats with chronic visceral hypersensitivity.SUN Chengcheng(孙程程),et al. Dept Gastroenterol,Peking Univ 1st Hosp,Beijing 100034.World Chin J Digestol 2010;18(14):1428-33. Objective To determine whether colonic serotonin transporter (SERT) expression is altered in rats with visceral hypersensitivity and to explore the

  4. General Information about Colon Cancer

    Science.gov (United States)

    ... The PDQ summaries are based on an independent review of the medical literature. They are not policy statements of the NCI or the NIH. Purpose of This Summary This PDQ cancer information summary has current information about the treatment of colon cancer. It is meant to inform and help ...

  5. Vitamin D and colon cancer

    Institute of Scientific and Technical Information of China (English)

    Lidija; Klampfer

    2014-01-01

    Calcitriol, 1α, 25-dihydroxyvitamin D3(1,25(OH)2D3), the most active form of vitamin D, is a pleotropic hormone with a wide range of biological activities. Due to its ability to regulate calcium and phosphate metabolism, 1,25D3 plays a major role in bone health. In addition, 1,25D3 binds to the vitamin D receptor and thereby regulates the expression of a number of genes which control growth, differentiation and survival of cancer cells. In agreement, the levels of vitamin D3 appear to be an essential determinant for the development and progression of colon cancer and supplementation with vitamin D3 is effective in suppressing intestinal tumorigenesis in animal models. Vitamin D3 has been estimated to lower the incidence of colorectal cancer by 50%, which is consistent with the inverse correlation between dietary vitamin D3 intake or sunlight exposure and human colorectal cancer. Several studies confirmed that increasing vitamin D3 lowers colon cancer incidence, reduces polyp recurrence, and that sufficient levels of vitamin D3 are associated with better overall survival of colon cancer patients. Vitamin D regulates the homeostasis of intestinal epithelium by modulating the oncogenic Wnt signaling pathway and by inhibiting tumor-promoting inflammation. Both activities contribute to the ability of 1,25D3 to prevent the development and progression of colon cancer.

  6. Colon Capsule Endoscopy: Review and Perspectives

    Directory of Open Access Journals (Sweden)

    David Friedel

    2016-01-01

    Full Text Available Colon capsule endoscopy utilizing PillCam COLON 2 capsule allows for visualization potentially of the entire colon and is currently approved for patients who cannot withstand the rigors of traditional optical colonoscopy (OC and associated sedation as well as those that had an OC that was incomplete for technical reasons other than a poor preparation. We will then describe the prior experience and current status of colon capsule endoscopy.

  7. Colonic urticaria pattern due to early ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Greenberg, H.M.; Goldberg, H.I.; Axel, L.

    1981-05-15

    The unusual radiographic pattern of bleb-like mounds on the surface of the colon mucosa, previously described as colonic urticaria, was seen in 3 patients in whom no allergic state was present. This urticaria-like pattern was due to colonic distention in all 3, and represented only submucosal edema on the gross and microscopic specimens. We hypothesize that this pattern is due to early changes of ischemia caused by colon distention.

  8. In vivo rat glandular stomach and colon micronucleus tests: Kinetics of micronucleated cells, apoptosis, and cell proliferation in the target tissues after a single oral administration of stomach- or colon-carcinogens.

    Science.gov (United States)

    Ohyama, Wakako; Okada, Emiko; Fujiishi, Yohei; Narumi, Kazunori; Yasutake, Nobuyoshi

    2013-08-15

    We have developed in vivo micronucleus (MN) tests by using an epithelial cell suspension isolated from the glandular stomach and colon of rodents. In the present study, our aim was to demonstrate the characteristics of the glandular stomach and colon MN tests by analyzing time-related changes in MN frequencies, apoptosis and cell proliferation in the target tissues of male CD (SD) rats that were orally administered a single dose of a stomach- or colon-targeted carcinogen, i.e., N-nitroso-N-methylurea (MNU) or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for the stomach and 1,2-dimethylhydrazine dihydrochloride (DMH) for the colon. After treatment, the MN frequencies significantly increased in the respective target tissues, peaking at 48-96h and decreasing afterwards. The time-response pattern could be explained by the epithelial cell turnover confirmed with a labeling experiment using the thymidine analog, 5-ethynyl-2'-deoxyuridine (EdU). In the study with MNU and DMH, we also prepared paraffin sections of the respective target tissues for the immunohistochemical evaluation of apoptosis and cell proliferation. The incidence of apoptosis increased in the early phase (6 and/or 24h) after treatment, and then decreased. Cell proliferation was depressed when a high incidence of apoptosis was observed, and then it recovered until 72h. MN frequencies increased with the recovery of cell proliferation occurring later than the peak apoptosis response. These results indicated that micronuclei were induced in the glandular stomach and colon epithelial cells by administration of the model chemicals. On the other hand, MNU induced significant increases of MNed cells in both the glandular stomach and bone marrow in the same rats, while MNNG did only in the glandular stomach when administered orally up to 1/4 of the LD50. These results suggest that the glandular stomach- and colon-MN tests would be useful for evaluating the genotoxicity of agents in the gastrointestinal tract.

  9. Congenital Diverticular Disease of the Entire Colon

    Directory of Open Access Journals (Sweden)

    A. Patel

    2013-01-01

    Full Text Available Congenital or true colonic diverticulosis is a rare condition typified by the preservation of the colonic wall architecture within the diverticular outpouching. Cases of multiple jejunal diverticula have been reported as well as cases of solitary giant diverticula of the colon. There have been no reports in the literature of pancolonic congenital diverticulosis.

  10. Congenital pouch colon and segmental dilatation of the colon: A report of two unusual cases

    Directory of Open Access Journals (Sweden)

    Archana Puri

    2011-01-01

    Full Text Available This report describes two unusual cases of anorectal malformation. The first had a type III congenital pouch colon with a colovesical fistula. In the other very similar case, segmental dilatation of the colon was present along with penoscrotal hypospadias and, distally, a length of normal colon ending in a rectourethral fistula. In both patients, the appendix was short, stubby and a Y-shaped duplication of the normal colon was present just proximal to the dilated segment of colon.

  11. Genotoxicity of quinolones: substituents contribution and transformation products QSAR evaluation using 2D and 3D models.

    Science.gov (United States)

    Li, Min; Wei, Dongbin; Zhao, Huimin; Du, Yuguo

    2014-01-01

    The genotoxicity of 21 quinolones antibiotics was determined using SOS/umu assay. Some quinolones exhibited high genotoxicity, and the chemical substituent on quinolone ring significantly affected genotoxicity. To establish the relationship between genotoxicity and substituent, a 2D-QSAR model based on quantum chemical parameters was developed. Calculation suggested that both steric and electrostatic properties were correlated well with genotoxicity. Furthermore, the specific effect on three key active sites (1-, 7- and 8-positions) of quinolone ring was investigated using a 3D-QSAR (comparative molecular field analysis, CoMFA) method. From our modeling, the genotoxicity increased when substituents had: (1) big volume and/or positive charge at 1-position; (2) negative charge at 7-position; and (3) small volume and/or negative charge at 8-position. The developed QSAR models were applicable to estimate genotoxicity of quinolones antibiotics and their transformation products. It is noted that some of the transformation products exhibited higher genotoxicity comparing to their precursor (e.g., ciprofloxacin). This study provided an alternative way to understand the molecule genotoxicity of quinolones derivatives, as well as to evaluate their potential environmental risks.

  12. Neoplastic transformation of breast epithelial cells by genotoxic stress

    Directory of Open Access Journals (Sweden)

    Raman Venu

    2010-06-01

    Full Text Available Abstract Background Exposure to genotoxic stresses such as radiation and tobacco smoke can cause increased cancer incidence rate as reflected in an in depth meta-analysis of data for women and breast cancer incidence. Published reports have indicated that exposures to low dose radiation and tobacco smoke are factors that contribute to the development of breast cancer. However, there is a scarcity of information on the combinatorial effects of low dose radiation and tobacco smoke on formation and progression of breast cancer. The combination of these two genotoxic insults can induce significant damage to the genetic material of the cells resulting in neoplastic transformation. Methods To study the effects of low dose ionizing radiation and tobacco smoke on breast cells, MCF 10A cells were treated either with radiation (Rad - 0.1 Gray or cigarette smoke condensate (Csc - 10 microgram/ml of medium or a combination of Rad + Csc. Following treatments, cells were analyzed for cell cycle distribution patterns and the ability to extrude the Hoechst 33342 dye. In addition, in vitro invasion and migration as well as mammosphere formation assays were performed. Finally, differential gene expression profiles were generated from the individual and combination treatment. Results Exposure of MCF 10A cells to the combination of radiation plus cigarette smoke condensate generated a neoplastic phenotype. The transformed phenotype promoted increased mammosphere numbers, altered cell cycle phases with a doubling of the population in S phase, and increased invasion and motility. Also, exclusion of Hoechst 33342 dye, a surrogate marker for increased ABC transporters, was observed, which indicates a possible increase in drug resistance. In addition, changes in gene expression include the up regulation of genes encoding proteins involved in metabolic pathways and inflammation. Conclusions The results indicate that when normal breast cells are exposed to low dose

  13. Polysaccharides in colon-specific drug delivery.

    Science.gov (United States)

    Sinha, V R; Kumria, R

    2001-08-14

    Natural polysaccharides are now extensively used for the development of solid dosage forms for delivery of drug to the colon. The rationale for the development of a polysaccharide based delivery system for colon is the presence of large amounts of polysaccharidases in the human colon as the colon is inhabited by a large number and variety of bacteria which secrete many enzymes e.g. beta-D-glucosidase, beta-D-galactosidase, amylase, pectinase, xylanase, beta-D-xylosidase, dextranase, etc. Various major approaches utilizing polysaccharides for colon-specific delivery are fermentable coating of the drug core, embedding of the drug in biodegradable matrix, formulation of drug-saccharide conjugate (prodrugs). A large number of polysaccharides have already been studied for their potential as colon-specific drug carrier systems, such as chitosan, pectin, chondroitin sulphate, cyclodextrin, dextrans, guar gum, inulin, amylose and locust bean gum. Recent efforts and approaches exploiting these polysaccharides in colon-specific drug delivery are discussed.

  14. Evaluation of the genotoxicity of process stream extracts from a coal gasification system.

    Science.gov (United States)

    Shimizu, R W; Benson, J M; Li, A P; Henderson, R F; Brooks, A L

    1984-01-01

    Extracts of three complex organic environmental mixtures, two from an experimental coal gasifier (a raw gas and a clean gas sample) and one from a coke oven main, were examined for genotoxicity. Three short-term genotoxicity assay systems were used: Ames Salmonella typhimurium reverse mutation assay, Chinese hamster ovary cell/hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) gene locus mutation assay, and the Chinese hamster lung primary culture/sister chromatid exchange (CHL/SCE) assay. Aroclor-1254-induced rat liver homogenate fraction (S-9) was required to observe genotoxicity in both gene locus mutation assays (CHO/HGPRT and Ames). The relative survival of CHO cells exposed to extracts was highest in cells exposed to clean gas samples, with the raw gas sample being the most cytotoxic either with or without the addition of S-9. All three complex mixtures induced sister chromatid exchanges in primary lung cell cultures without the addition of S-9. The relative genotoxicity ranking of the samples varied between the mammalian and prokaryotic assay systems. Coke oven main extract produced fewer revertants in bacteria than the raw gas sample. However, the coke oven main extract was more genotoxic in the two eukaryotic systems (CHL/SCE and CHO/HGPRT) than was the raw gas sample. The results of all three assays indicate that the cleanup process used in the experimental gasifier was effective in decreasing the genotoxic materials in the process stream. These data also reemphasize the necessity of evaluating genotoxicity of complex mixtures in a variety of short-term systems.

  15. The cytotoxicity and genotoxicity of soluble and particulate cobalt in human lung fibroblast cells

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Leah J.; Holmes, Amie L. [Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Maine Center for Environmental Toxicology and Health, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Department of Applied Medical Science, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Kandpal, Sanjeev Kumar; Mason, Michael D. [Department of Chemical and Biological Engineering, University of Maine, Orono, ME (United States); Zheng, Tongzhang [Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT (United States); Wise, John Pierce, E-mail: John.Wise@usm.maine.edu [Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Maine Center for Environmental Toxicology and Health, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Department of Applied Medical Science, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States)

    2014-08-01

    Cobalt exposure is increasing as cobalt demand rises worldwide due to its use in enhancing rechargeable battery efficiency, super-alloys, and magnetic products. Cobalt is considered a possible human carcinogen with the lung being a primary target. However, few studies have considered cobalt-induced toxicity in human lung cells. Therefore, in this study, we sought to determine the cytotoxicity and genotoxicity of particulate and soluble cobalt in human lung cells. Cobalt oxide and cobalt chloride were used as representative particulate and soluble cobalt compounds, respectively. Exposure to both particulate and soluble cobalt induced a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ion levels. Based on intracellular cobalt ion levels, we found that soluble cobalt was more cytotoxic than particulate cobalt while particulate and soluble cobalt induced similar levels of genotoxicity. However, soluble cobalt induced cell cycle arrest indicated by the lack of metaphases at much lower intracellular cobalt concentrations compared to cobalt oxide. Accordingly, we investigated the role of particle internalization in cobalt oxide-induced toxicity and found that particle-cell contact was necessary to induce cytotoxicity and genotoxicity after cobalt exposure. These data indicate that cobalt compounds are cytotoxic and genotoxic to human lung fibroblasts, and solubility plays a key role in cobalt-induced lung toxicity. - Highlights: • Particulate and soluble cobalt are cytotoxic and genotoxic to human lung cells. • Soluble cobalt induces more cytotoxicity compared to particulate cobalt. • Soluble and particulate cobalt induce similar levels of genotoxicity. • Particle-cell contact is required for particulate cobalt-induced toxicity.

  16. The combined bacterial Lux-Fluoro test for the detection and quantification of genotoxic and cytotoxic agents in surface water: results from the "Technical Workshop on Genotoxicity Biosensing".

    Science.gov (United States)

    Baumstark-Khan, Christa; Rabbow, Elke; Rettberg, Petra; Horneck, Gerda

    2007-12-15

    The bioassay Lux-Fluoro test was developed for the rapid detection and quantification of environmental pollutants with genotoxic and/or cytotoxic potential. This bacterial test system uses two different reporter genes whose gene products and their reactions, respectively, can be measured easily and simultaneously by optical methods. Genotoxicity is measured by the increase of bioluminescence in genetically modified bacteria which carry a plasmid with a complete lux operon for the enzyme luciferase from the marine photobacterium P. leiognathi under the control of a DNA-damage dependent so-called SOS promoter. If the deoxyribonucleic acid in these bacteria is damaged by a genotoxic chemical, the SOS promoter is turned on and the lux operon is expressed. The newly synthesized luciferase reacts immediately with its substrate thereby producing bioluminescence in a damage-proportional manner. In the second part of the system, genetically modified bacteria carry the gene for the green fluorescent protein (gfp) from the jellyfish Aequora victoria downstream from a constitutively expressed promoter. These bacteria are fluorescent under common growth conditions. If their cellular metabolism is disturbed by the action of cytotoxic chemicals, the fluorescence decreases in a dose-proportional manner. The combined Lux-Fluoro test is shown to be well suited for the biological assessment of the geno- and cytotoxicity of a series of model agents and environmental samples at the Technical Workshop on Genotoxicity Biosensing (TECHNOTOX).

  17. Colonic perforation in Behcet's syndrome

    Institute of Scientific and Technical Information of China (English)

    Catherine M Dowling; Arnold DK Hill; Carmel Malone; John J Sheehan; Shona Tormey; Kieran Sheahan; Enda McDermott; Niall J O'Higgins

    2008-01-01

    A 17-year-old gentleman was admitted to our hospital for headache, the differential diagnosis of which included Behcet's syndrome (BS). He developed an acute abdomen and was found to have air under the diaphragm on erect chest X-ray. Subsequent laparotomy revealed multiple perforations throughout the colon. This report describes an unusual complication of Behcets syndrome occurring at the time of presentation and a review of the current literature of reported cases.

  18. Colonic perforation in Behcet's syndrome.

    Science.gov (United States)

    Dowling, Catherine-M; Hill, Arnold-Dk; Malone, Carmel; Sheehan, John-J; Tormey, Shona; Sheahan, Kieran; McDermott, Enda; O'Higgins, Niall-J

    2008-11-14

    A 17-year-old gentleman was admitted to our hospital for headache, the differential diagnosis of which included Behcet's syndrome (BS). He developed an acute abdomen and was found to have air under the diaphragm on erect chest X-ray. Subsequent laparotomy revealed multiple perforations throughout the colon. This report describes an unusual complication of Behcets syndrome occurring at the time of presentation and a review of the current literature of reported cases.

  19. Cholesterol excretion and colon cancer.

    Science.gov (United States)

    Broitman, S A

    1981-09-01

    Populations consuming diets high in fat and cholesterol exhibit a greater incidence of colon cancer than those consuming less fat and cholesterol. Lowering elevated serum cholesterol levels experimentally or clinically is associated with increased large-bowel tumorigenesis. Thus, cholesterol lost to the gut, either dietary or endogenously synthesized, appears to have a role in large-bowel cancer. Whether the effect(s) is mediated by increases in fecal bile acid excretion or some other mechanism is not clear.

  20. Late colonization of Easter Island.

    Science.gov (United States)

    Hunt, Terry L; Lipo, Carl P

    2006-03-17

    Easter Island (Rapa Nui) provides a model of human-induced environmental degradation. A reliable chronology is central to understanding the cultural, ecological, and demographic processes involved. Radiocarbon dates for the earliest stratigraphic layers at Anakena, Easter Island, and analysis of previous radiocarbon dates imply that the island was colonized late, about 1200 A.D. Substantial ecological impacts and major cultural investments in monumental architecture and statuary thus began soon after initial settlement.

  1. Primary lymphoma of the colon

    Directory of Open Access Journals (Sweden)

    Tauro Leo

    2009-01-01

    Full Text Available Primary lymphoma of the colon is a rare tumor of the gastrointestinal (GI tract and comprises only 0.2-1.2% of all colonic malignancies. The most common variety of colonic lymphoma is non-Hodgkin′s lymphoma (NHL. The GI tract is the most frequently involved site, accounting for 30-40% of all extra nodal lymphomas, approximately 4-20% of which are NHL. The stomach is the most common location of GI lymphomas, followed by the small intestine. Early diagnosis may prevent intestinal perforation; however, the diagnosis is often delayed in most cases. Therapeutic approaches described in two subsets include: Radical tumor resection (hemicolectomy plus multi-agent chemotherapy (polychemotherapy in early stage patients, biopsy plus multidrug chemotherapy in advanced stage patients. Radiotherapy is reserved for specific cases; surgery alone can be considered as an adequate treatment for patients with low-grade NHL disease that does not infiltrate beyond the sub mucosa. Although resection plays an important role in the local control of the disease and in preventing bleeding and/or perforation, it rarely eradicates the lymphoma by itself. Those with limited stage disease may enjoy prolonged survival when treated with aggressive chemotherapy.

  2. Anodically Grown Titania Nanotube Induced Cytotoxicity has Genotoxic Origins

    Science.gov (United States)

    Mohamed, M. Sheikh; Torabi, Aida; Paulose, Maggie; Kumar, D. Sakthi; Varghese, Oomman K.

    2017-02-01

    Nanoarchitectures of titania (TiO2) have been widely investigated for a number of medical applications including implants and drug delivery. Although titania is extensively used in the food, drug and cosmetic industries, biocompatibility of nanoscale titania is still under careful scrutiny due to the conflicting reports on its interaction with cellular matter. For an accurate insight, we performed in vitro studies on the response of human dermal fibroblast cells toward pristine titania nanotubes fabricated by anodic oxidation. The nanotubes at low concentrations were seen to induce toxicity to the cells, whereas at higher concentrations the cell vitality remained on par with controls. Further investigations revealed an increase in the G0 phase cell population depicting that majority of cells were in the resting rather than active phase. Though the mitochondrial set-up did not exhibit any signs of stress, significantly enhanced reactive oxygen species production in the nuclear compartment was noted. The TiO2 nanotubes were believed to have gained access to the nuclear machinery and caused increased stress leading to genotoxicity. This interesting property of the nanotubes could be utilized to kill cancer cells, especially if the nanotubes are functionalized for a specific target, thus eliminating the need for any chemotherapeutic agents.

  3. Genotoxicity induced by saponified coconut oil surfactant in prokaryote systems.

    Science.gov (United States)

    Petta, Tirzah Braz; de Medeiros, Sílvia Regina Batistuzzo; do Egito, Eryvaldo Sócrates Tabosa; Agnez-Lima, Lucymara Fassarella

    2004-11-01

    Surfactants are amphiphilic substances with special properties and chemical structures that allow a reduction in interfacial tension, which permits an increase in molecule solubilization. The critical micelle concentration (CMC) is an important characteristic of surfactants that determines their aggregate state, which is generally related to its functional mechanism. In this work the genotoxic potential of saponified coconut oil (SCO), a surfactant obtained from Cocos nucifera, was analyzed using prokaryote systems. DNA strand breaks were not observed after treatment of a plasmid with SCO. Negative results were also obtained in the SOS Chromotest using Escherichia coli strains PQ35 and PQ37. A moderate toxicity of SCO was observed after treatment of strain CC104 with a concentration above its CMC, in which micelles were found. Nevertheless, this treatment was not cytotoxic to a CC104mutMmutY strain. Furthermore, in this DNA repair-deficient strain treatment with a SCO dose below its CMC, in which only monomers were found, demonstrated the possibility of an antioxidant effect, since a reduction in spontaneous mutagenesis frequency was observed. Finally, in an Ames test without metabolic activation mutagenicity induction was observed in strains TA100 and TA104 with treatment doses below the CMC. The cytotoxic, antioxidant and mutagenic effects of SCO can be influenced by the aggregational state.

  4. Genotoxic Effects of Culture Media on Human Pluripotent Stem Cells

    Science.gov (United States)

    Prakash Bangalore, Megha; Adhikarla, Syama; Mukherjee, Odity; Panicker, Mitradas M.

    2017-01-01

    Culture conditions play an important role in regulating the genomic integrity of Human Pluripotent Stem Cells (HPSCs). We report that HPSCs cultured in Essential 8 (E8) and mTeSR, two widely used media for feeder-free culturing of HPSCs, had many fold higher levels of ROS and higher mitochondrial potential than cells cultured in Knockout Serum Replacement containing media (KSR). HPSCs also exhibited increased levels of 8-hydroxyguanosine, phospho-histone-H2a.X and p53, as well as increased sensitivity to γ-irradiation in these two media. HPSCs in E8 and mTeSR had increased incidence of changes in their DNA sequence, indicating genotoxic stress, in addition to changes in nucleolar morphology and number. Addition of antioxidants to E8 and mTeSR provided only partial rescue. Our results suggest that it is essential to determine cellular ROS levels in addition to currently used criteria i.e. pluripotency markers, differentiation into all three germ layers and normal karyotype through multiple passages, in designing culture media. PMID:28176872

  5. Identification of consensus biomarkers for predicting non-genotoxic hepatocarcinogens

    Science.gov (United States)

    Huang, Shan-Han; Tung, Chun-Wei

    2017-01-01

    The assessment of non-genotoxic hepatocarcinogens (NGHCs) is currently relying on two-year rodent bioassays. Toxicogenomics biomarkers provide a potential alternative method for the prioritization of NGHCs that could be useful for risk assessment. However, previous studies using inconsistently classified chemicals as the training set and a single microarray dataset concluded no consensus biomarkers. In this study, 4 consensus biomarkers of A2m, Ca3, Cxcl1, and Cyp8b1 were identified from four large-scale microarray datasets of the one-day single maximum tolerated dose and a large set of chemicals without inconsistent classifications. Machine learning techniques were subsequently applied to develop prediction models for NGHCs. The final bagging decision tree models were constructed with an average AUC performance of 0.803 for an independent test. A set of 16 chemicals with controversial classifications were reclassified according to the consensus biomarkers. The developed prediction models and identified consensus biomarkers are expected to be potential alternative methods for prioritization of NGHCs for further experimental validation.

  6. Assessment of mutagenic, antimutagenic and genotoxicity effects of Mimosa tenuiflora

    Directory of Open Access Journals (Sweden)

    Viviane A. Silva

    2013-04-01

    Full Text Available Genotoxic effects of Mimosa tenuiflora (Willd. Poir, Fabaceae, were investigated by using both micronucleus test and bacterial reverse mutation assay in Salmonella typhimurium TA97, TA98, TA100, TA102 respectively. In respect of Ames test results show that the extract does not induce mutations in any strains of Salmonella typhimurium tested since the mutagenicity index is less than 2. In the antimutagenic effect was observed that the extract at the concentrations tested significantly decreased the mutagenicity index of all strains tested which characterized the extract as antimutagenic in these conditions. In the micronucleus test in vivo, we observed that the concentrations used did not induce an increase in the frequency of micronucleus in normochromatic erythrocytes of mice. Therefore, we concluded that the extract of M. tenuiflora is not mutagenic in the absence of exogenous metabolizing system and does not induce an increase in the frequency of the micronucleus characterized as an agent not mutagenic in these conditions. Further studies of toxicity need to be made to the use of this plant in the treatment of diseases to be stimulated.

  7. Radio frequency electromagnetic fields: cancer, mutagenesis, and genotoxicity.

    Science.gov (United States)

    Heynick, Louis N; Johnston, Sheila A; Mason, Patrick A

    2003-01-01

    We present critiques of epidemiologic studies and experimental investigations, published mostly in peer-reviewed journals, on cancer and related effects from exposure to nonionizing electromagnetic fields in the nominal frequency range of 3 kHz to 300 GHz of interest to Subcommittee 4 (SC4) of the International Committee on Electromagnetic Safety (ICES). The major topics discussed are presented under the headings Epidemiologic and Other Findings on Human Exposure, Mammals Exposed In Vivo, Mammalian Live Tissues and Cell Preparations Exposed In Vitro, and Mutagenesis and Genotoxicity in Microorganisms and Fruit Flies. Under each major topic, we present minireviews of papers on various specific endpoints investigated. The section on Epidemiologic and Other Findings on Human Exposure is divided into two subsections, the first on possible carcinogenic effects of exposure from emitters not in physical contact with the populations studied, for example, transmitting antennas and other devices. Discussed in the second subsection are studies of postulated carcinogenic effects from use of mobile phones, with prominence given to brain tumors from use of cellular and cordless telephones in direct physical contact with an ear of each subject. In both subsections, some investigations yielded positive findings, others had negative findings, including papers directed toward experimentally verifying positive findings, and both were reported in a few instances. Further research on various important aspects may resolve such differences. Overall, however, the preponderance of published epidemiologic and experimental findings do not support the supposition that in vivo or in vitro exposures to such fields are carcinogenic.

  8. A Study on Genotoxicity of Cooking Fume from Rapessed Oil

    Institute of Scientific and Technical Information of China (English)

    CHENHUA; YANGMINGDING; 等

    1992-01-01

    The present article reports the genotoxic potential of rapeseed oil cooking fume investigated by a battery of short-term tests(Ames test,SCE/V79 in vitor and mice micronucleus in vivo test).The results showed that the cooking fume contained mutagenic activity.In the presence of S9 mix,an increase in the number of the Salmonella TA98 was observed at doses ranging from 1.0 to 5.0mg/plate,and the SCE frequencies of V79 cell were markedly raised at doses ranging from 0.05 to 0.5mg·m-1.The positive result was also obtained in mice micronucleus assay,the mice had inhaled the cooking fume a week earlier.The requency of mice bone marrow MN-PCR ws increased and it showed a remarkable time-dose-response relationship during the 4 weeks exposure.The results suggested that this cooking fume exposure may be a risk factor of lung cancer in Chinese women.

  9. Examination of genotoxic effects of fumagillin in vivo

    Directory of Open Access Journals (Sweden)

    Kulić Milan

    2009-01-01

    Full Text Available Fumagillin is an antibiotic derived from the fungus Aspergillus fumigatus. It has been used successfully for the treatment of intestinal microsporidiosis in HIV-positive humans, as well as in those suffering from intestinal amebiasis and microsporidial keratoconjunctivitis. In veterinary medicine it is approved for the treatment of microsporidiosis in bees and fish. In this research fumagillin was tested for the ability to provoke chromosomal aberrations in mouse bone marrow cells. BALB/c mice were administered fumagillin by gastric probe in doses of 5, 10 and 20 mg/kg b.w. Water-sugary syrup was the negative and cyclophosphamide (15 mg/kg b.w. the positive control. Significantly increased frequencies (p<0.01 or p<0.001 of numerical chromosomal aberrations (aneuploidies and poliploidies was observed both in the medium (10 mg/kg b.w. and the highest (20 mg/kg b.w. dose of fumagillin. Structural chromosomal aberrations (gaps, breaks and insertions were noticeably more frequent in comparison to negative control only in the highest experimental dose of dycikloheksilamine. These results clearly showed that fumagillin in concetrations 10 and 20 mg/kg b.w. had a genotoxic potential in vivo.

  10. Transgenic Plants as Sensors of Environmental Pollution Genotoxicity

    Science.gov (United States)

    Kovalchuk, Igor; Kovalchuk, Olga

    2008-01-01

    Rapid technological development is inevitably associated with many environmental problems which primarily include pollution of soil, water and air. In many cases, the presence of contamination is difficult to assess. It is even more difficult to evaluate its potential danger to the environment and humans. Despite the existence of several whole organism-based and cell-based models of sensing pollution and evaluation of toxicity and mutagenicity, there is no ideal system that allows one to make a quick and cheap assessment. In this respect, transgenic organisms that can be intentionally altered to be more sensitive to particular pollutants are especially promising. Transgenic plants represent an ideal system, since they can be grown at the site of pollution or potentially dangerous sites. Plants are ethically more acceptable and esthetically more appealing than animals as sensors of environmental pollution. In this review, we will discuss various transgenic plant-based models that have been successfully used for biomonitoring genotoxic pollutants. We will also discuss the benefits and potential drawbacks of these systems and describe some novel ideas for the future generation of efficient transgenic phytosensors.

  11. Does an extract of carob (Ceratonia siliqua L.) have chemopreventive potential related to oxidative stress and drug metabolism in human colon cells?

    Science.gov (United States)

    Klenow, Stefanie; Jahns, Franziska; Pool-Zobel, Beatrice L; Glei, Michael

    2009-04-08

    Phenolic ingredients of an aqueous carob extract are well characterized and consist of mainly gallic acid (GA). In order to assess possible chemopreventive mechanisms of carob, which can be used as a cacao substitute, effects on expression of genes related to stress response and drug metabolism were studied using human colon cell lines of different transformation state (LT97 and HT29). Stress-related genes, namely catalase (CAT) and superoxide dismutase (SOD2), were induced by carob extract and GA in LT97 adenoma, but not in HT29 carcinoma cells. Although corresponding protein products and enzyme activities were not elevated, pretreatment with carob extract and GA for 24 h reduced DNA damage in cells challenged with hydrogen peroxide (H(2)O(2)). In conclusion, carob extract and its major phenolic ingredient GA modulate gene expression and protect colon adenoma cells from genotoxic impact of H(2)O(2). Upregulation of stress-response genes could not be related to functional consequences.

  12. Protective Effects of Quercetin against Dimethoate-Induced Cytotoxicity and Genotoxicity in Allium sativum Test.

    Science.gov (United States)

    Ahmad, Waseem; Shaikh, Sibhghatulla; Nazam, Nazia; Lone, Mohammad Iqbal

    2014-01-01

    The present investigation was directed to study the possible protective activity of quercetin-a natural antioxidant against dimethoate-induced cyto- and genotoxicity in meristematic cells of Allium sativum. So far there is no report on the biological properties of quercetin in plant test systems. Chromosome breaks, multipolar anaphase, stick chromosome, and mitotic activity were undertaken in the current study as markers of cyto- and genotoxicity. Untreated control, quercetin controls (@ 5, 10 and 20 μg/mL for 3 h), and dimethoate exposed groups (@ 100 and 200 μg/mL for 3 h) were maintained. For protection against cytogenotoxicity, the root tip cells treated with dimethoate at 100 and 200 μg/mL for 3 h and quercetin treatment at 5, 10, and 20 μg/mL for 16 h, prior to dimethoate treatment, were undertaken. Quercetin was found to be neither cytotoxic nor genotoxic in Allium sativum control at these doses. A significant increase (P < 0.05) in chromosomal aberrations was noted in dimethoate treated Allium. Pretreatment of Allium sativum with quercetin significantly (P < 0.05) reduced dimethoate-induced genotoxicity and cytotoxicity in meristematic cells, and these effects were dose dependent. In conclusion, quercetin has a protective role in the abatement of dimethoate-induced cyto- and genotoxicity in the meristematic cells of Allium sativum that resides, at least in part, on its antioxidant effects.

  13. 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.

  14. Genotoxicity of intraperitoneal injection of lipoamphiphile CdSe/ZnS quantum dots in rats.

    Science.gov (United States)

    Aye, Mélanie; Di Giorgio, Carole; Mekaouche, Mourad; Steinberg, Jean-Guillaume; Brerro-Saby, Christelle; Barthélémy, Philippe; De Méo, Michel; Jammes, Yves

    2013-12-12

    The main objective of the present in vivo rat study was to determine the genotoxicity of lipoamphiphile-coated CdSe/ZnS Quantum Dots (QDs), in several organs (brain, liver, kidneys, lungs and testicles). The second objective was to establish the correlations between the QDs genotoxic activity and the oxidative stress, the production of a proinflammatory cytokine (TNF-α), a stress-induced chaperone protein, the phosphorylated heat shock protein 70 (pHsp70), and an increase in the caspase-3 apoptosis factor. Four QDs doses were injected into the peritoneal cavity (5, 5×10(-1), 5×10(-2) and 5×10(-3)μg/kg). DNA lesions in the different organs were measured by the comet assay, and chromosome abnormalities were evaluated by the micronucleus assay on blood reticulocytes (MNRET). Twenty-four hours after the QDs injection, genotoxic effects were observed in the brain and liver and, only for the highest QDs concentration, in testicles. No genotoxic effect was seen in the kidney and lung. The MNRET test revealed a dose-response induction of micronuclei. In parallel, we did neither reveal oxidative stress nor significant variations of TNF-α, pHsp70, and caspase-3. In conclusion, the QDs exerted significant genotoxic effects in the brain and liver, even in the absence of any associated oxidative stress and inflammatory processes.

  15. Ecotoxicological and Genotoxic Evaluation of Buenos Aires City (Argentina Hospital Wastewater

    Directory of Open Access Journals (Sweden)

    Anahí Magdaleno

    2014-01-01

    Full Text Available 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 performed using the green algae Pseudokirchneriella subcapitata and the Allium cepa test, respectively. Toxicity assay showed that 55% of the samples were toxic to the algae (%I of growth between 23.9 and 54.8. The A. cepa test showed that 40% of the samples were genotoxic. The analysis of chromosome aberrations (CA and micronucleus (MN showed no significant differences between days and significant differences between months. The sample from the STP was not genotoxic to A. cepa but toxic to the algae (%I = 41%, showing that sewage treatment was not totally effective. This study highlights the need for environmental control programs and the establishment of advanced and effective effluent treatment plants in the hospitals, which are merely dumping the wastewaters in the municipal sewerage system.

  16. The cytotoxicity and genotoxicity of soluble and particulate cobalt in human lung fibroblast cells.

    Science.gov (United States)

    Smith, Leah J; Holmes, Amie L; Kandpal, Sanjeev Kumar; Mason, Michael D; Zheng, Tongzhang; Wise, John Pierce

    2014-08-01

    Cobalt exposure is increasing as cobalt demand rises worldwide due to its use in enhancing rechargeable battery efficiency, super-alloys, and magnetic products. Cobalt is considered a possible human carcinogen with the lung being a primary target. However, few studies have considered cobalt-induced toxicity in human lung cells. Therefore, in this study, we sought to determine the cytotoxicity and genotoxicity of particulate and soluble cobalt in human lung cells. Cobalt oxide and cobalt chloride were used as representative particulate and soluble cobalt compounds, respectively. Exposure to both particulate and soluble cobalt induced a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ion levels. Based on intracellular cobalt ion levels, we found that soluble cobalt was more cytotoxic than particulate cobalt while particulate and soluble cobalt induced similar levels of genotoxicity. However, soluble cobalt induced cell cycle arrest indicated by the lack of metaphases at much lower intracellular cobalt concentrations compared to cobalt oxide. Accordingly, we investigated the role of particle internalization in cobalt oxide-induced toxicity and found that particle-cell contact was necessary to induce cytotoxicity and genotoxicity after cobalt exposure. These data indicate that cobalt compounds are cytotoxic and genotoxic to human lung fibroblasts, and solubility plays a key role in cobalt-induced lung toxicity.

  17. Ogg1 genetic background determines the genotoxic potential of environmentally relevant arsenic exposures.

    Science.gov (United States)

    Bach, Jordi; Sampayo-Reyes, Adriana; Marcos, Ricard; Hernández, Alba

    2014-03-01

    Inorganic arsenic (i-As) is a well-established human carcinogen to which millions of people are exposed worldwide. It is generally accepted that the genotoxic effects of i-As after an acute exposure are partially linked to the i-As-induced production of reactive oxygen species, but it is necessary to better determine whether chronic sub-toxic i-As doses are able to induce biologically significant levels of oxidative DNA damage (ODD). To fill in this gap, we have tested the genotoxic and oxidative effects of environmentally relevant arsenic exposures using mouse embryonic fibroblast MEF mutant Ogg1 cells and their wild-type counterparts. Effects were examined by using the comet assay complemented with the use of FPG enzyme. Our findings indicate that MEF Ogg1-/- cells are more sensitive to arsenite-induced acute toxicity, genotoxicity and ODD. Long-term exposure to sub-toxic doses of arsenite generates a detectable increase in ODD and genotoxic DNA damage only in MEF Ogg1-deficient cells. Altogether, the data presented here point out the relevance of ODD and Ogg1 genetic background on the genotoxic risk of i-As at environmentally plausible doses. The persistent accumulation of DNA 8-OH-dG lesions in Ogg1-/- cells during the complete course of the exposure suggests a relevant role in arsenic-associated carcinogenic risk in turn.

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

    Energy Technology Data Exchange (ETDEWEB)

    Han, Min; Ryu, Tae Ho; Hyun, Kyung Man; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Wilhelmova, Nad [Institute of Experimental Botany, Prague (Czech Republic)

    2010-05-15

    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

  19. On the Relationship Between the Colonizers and the Colonized in“Shooting an Elephant”

    Institute of Scientific and Technical Information of China (English)

    Pan Li

    2015-01-01

    George Orwell’s“Shooting an Elephant”is reputed as one of his best works for its artistry and keenness. In this essay, the relationship between the colonizers and the colonized is interesting and worth researching. The author of this thesis holds the opinion that besides the common fact that the colonizers dominate the colonized, the colonized, in reverse, also dominate the British colonizers in the text. And this kind of domination is through two aspects, namely the weakness of human nature and the imperialistic creed.

  20. Malakoplakia of the colon associated with colonic adenocarcinoma diagnosed in colonic biopsies

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Malakoplakia, typically involving the urinary tract, is an uncommon form of chronic inflammation caused by chronic nfections and characterized by accumulation of macrophages. It has also been found in many other sites such as the gastrointestinal tract, pancreas, liver, lymph Snodes, skin, respiratory tract, adrenal gland, vagina and brain. We present a case of a 64-year-old man referred to our hospital with cachexia and radiologic evidence of metastatic tumor of the liver.Colonoscopy revealed a large malignant-appearing polypoid mass of the ascending colon and multiple distinct polyps throughout the rest of the colon. Biopsies of the ascending colon mass confirmed the diagnosis of adenocarcinoma.Histological examination of two of the other polyps revealed malakoplakia which was characterized by aggregates of granular histiocytes with Michaelis-Gutmann bodies and histochemically confirmed with periodic acid-Schiff and von Kossa stains. This is a rare case diagnosed on endoscopic samples. The majority of reported cases were found in surgical specimens. In addition, the endoscopic appearance of multiple polyps is unusual in malakoplakia.

  1. Anti-genotoxic ability of α-tocopherol and Anthocyanin to counteract fish DNA damage induced by musk xylene.

    Science.gov (United States)

    Rocco, Lucia; Mottola, Filomena; Santonastaso, Marianna; Saputo, Valentina; Cusano, Elena; Costagliola, Domenico; Suero, Teresa; Pacifico, Severina; Stingo, Vincenzo

    2015-11-01

    Many compounds released into the environment are able to interact with genetic material. The main purpose of genetic toxicology is to investigate the adverse effects of genotoxic molecules such as reduced fitness, changes in gene frequencies and their impact on genetic diversity in populations following genotoxic exposure. However, the ecological effects of many genotoxic compounds remain poorly understood. The aim of this research was to evaluate the genotoxic activity of an artificial musk (musk xylene, MX) and the potential anti-genotoxicity against this chemical compound of two antioxidant substances (α-tocopherol and an anthocyanins enriched extract). The studies were performed both in vivo and in vitro, using the teleost Danio rerio and the DLEC (Dicentrarchus labrax embryonic cells) cell line. We carried out the exposure to these substances at different times. DNA and cell damage and their possible repair were detected by various experimental approaches: DNA strand breaks (Comet Assay), degree of apoptosis (Diffusion Assay) and molecular alterations at the genomic level (RAPD-PCR technique). Data were collected and analyzed for statistical significance using the Student's t test. The results of this study showed that MX exhibited a genotoxic activity even after short exposure times. The anti-genotoxicity experiments evidenced that both α-tocopherol and Anthocyanin were able to contrast the genotoxic effects induced by MX, both in vivo and in vitro.

  2. Metabolism links bacterial biofilms and colon carcinogenesis.

    Science.gov (United States)

    Johnson, Caroline H; Dejea, Christine M; Edler, David; Hoang, Linh T; Santidrian, Antonio F; Felding, Brunhilde H; Ivanisevic, Julijana; Cho, Kevin; Wick, Elizabeth C; Hechenbleikner, Elizabeth M; Uritboonthai, Winnie; Goetz, Laura; Casero, Robert A; Pardoll, Drew M; White, James R; Patti, Gary J; Sears, Cynthia L; Siuzdak, Gary

    2015-06-02

    Bacterial biofilms in the colon alter the host tissue microenvironment. A role for biofilms in colon cancer metabolism has been suggested but to date has not been evaluated. Using metabolomics, we investigated the metabolic influence that microbial biofilms have on colon tissues and the related occurrence of cancer. Patient-matched colon cancers and histologically normal tissues, with or without biofilms, were examined. We show the upregulation of polyamine metabolites in tissues from cancer hosts with significant enhancement of N(1), N(12)-diacetylspermine in both biofilm-positive cancer and normal tissues. Antibiotic treatment, which cleared biofilms, decreased N(1), N(12)-diacetylspermine levels to those seen in biofilm-negative tissues, indicating that host cancer and bacterial biofilm structures contribute to the polyamine metabolite pool. These results show that colonic mucosal biofilms alter the cancer metabolome to produce a regulator of cellular proliferation and colon cancer growth potentially affecting cancer development and progression.

  3. Metabolism links bacterial biofilms and colon carcinogenesis

    Science.gov (United States)

    Johnson, Caroline H.; Dejea, Christine M.; Edler, David; Hoang, Linh T.; Santidrian, Antonio F.; Felding, Brunhilde H.; Cho, Kevin; Wick, Elizabeth C.; Hechenbleikner, Elizabeth M.; Uritboonthai, Winnie; Goetz, Laura; Casero, Robert A.; Pardoll, Drew M.; White, James R.; Patti, Gary J.; Sears, Cynthia L.; Siuzdak, Gary

    2015-01-01

    SUMMARY Bacterial biofilms in the colon alter the host tissue microenvironment. A role for biofilms in colon cancer metabolism has been suggested but to date has not been evaluated. Using metabolomics, we investigated the metabolic influence that microbial biofilms have on colon tissues and the related occurrence of cancer. Patient-matched colon cancers and histologically normal tissues, with or without biofilms, were examined. We show the upregulation of polyamine metabolites in tissues from cancer hosts with significant enhancement of N1, N12-diacetylspermine in both biofilm positive cancer and normal tissues. Antibiotic treatment, which cleared biofilms, decreased N1, N12-diacetylspermine levels to those seen in biofilm negative tissues, indicating that host cancer and bacterial biofilm structures contribute to the polyamine metabolite pool. These results show that colonic mucosal biofilms alter the cancer metabolome, to produce a regulator of cellular proliferation and colon cancer growth potentially affecting cancer development and progression. PMID:25959674

  4. Recent changes of colonic diverticulosis in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kun Sang; Lee, Kwan Seh; Choi, Sun Seob; Song, In Sup [Chung Ang University College of Medicine, Seoul (Korea, Republic of)

    1984-09-15

    Colonic diverticulosis in Korea was considered as a rare disease, but recently increasing tendency of colonic diverticulosis were reported, and right side preponderance was also noted compared with left side preponderance of western country. Authors reviewed 818 cases of colon study performed from Jan. 1st 1982 to May 31th, 1984 at the Department of Radiology, Chung Ang University Hospital. The results were as follows. 1. Diverticuli of colon were observed in 45 cases (5.5%) out of 818 colon study. 2. Male is more frequently affected (32 out of 441, 7.2%) than female (13 out of 377, 3.5%). 3. 5th decade is the predilection age group but occurrence in younger age group is increasing. 4. Diverticulosis may occur single or multiple with variable size in entire colon except rectum but right side preponderance is remarkable. 5. Complication were observed in 6 cases (13.3%)

  5. Tubular Colonic Duplication Presenting as Rectovestibular Fistula.

    Science.gov (United States)

    Karkera, Parag J; Bendre, Pradnya; D'souza, Flavia; Ramchandra, Mukunda; Nage, Amol; Palse, Nitin

    2015-09-01

    Complete colonic duplication is a very rare congenital anomaly that may have different presentations according to its location and size. Complete colonic duplication can occur in about 15% of all gastrointestinal duplications. Double termination of tubular colonic duplication in the perineum is even more uncommon. We present a case of a Y-shaped tubular colonic duplication which presented with a rectovestibular fistula and a normal anus. Radiological evaluation and initial exploration for sigmoidostomy revealed duplicated colons with a common vascular supply. Endorectal mucosal resection of theduplicated distal segment till the colostomy site with division of the septum of the proximal segment and colostomy closure proved curative without compromise of the continence mechanism. Tubular colonic duplication should always be ruled out when a diagnosis of perineal canal is considered in cases of vestibular fistula alongwith a normal anus.

  6. Cytotoxic, genotoxic and mutagenic effects of sewage sludge on Allium cepa.

    Science.gov (United States)

    Corrêa Martins, Maria Nilza; de Souza, Victor Ventura; da Silva Souza, Tatiana

    2016-04-01

    The objective of this study was to ascertain the cytotoxic, genotoxic and mutagenic potential of sewage sludge using Allium cepa bioassay. Solubilized and crude sludge from two sewage treatment stations (STSs), herein named JM and M, were tested. In addition, sanitized, crude and solubilized sludge were also analyzed from STS M. The treatments showed positive response to phytotoxicity, cytotoxicity, genotoxicity and/or mutagenicity. Despite negative results for MN F1 (micronuclei counted in F1 root cells, derived from meristematic cells), the monitoring of genotoxic and mutagenic activities of sewage sludge are recommended because in agricultural areas this residue is applied in large scale and continuously. Based on our results we advise caution in the use of sewage sludge in agricultural soils.

  7. Genotoxicity evaluation of dimethoate to experimental mice by micronucleus, chromosome aberration tests, and comet assay.

    Science.gov (United States)

    Ayed-Boussema, Imen; Rjiba, Karima; Mnasri, Nourhène; Moussa, Amal; Bacha, Hassen

    2012-01-01

    Dimethoate (DM) is an organophosphate insecticide with numerous uses on field and agricultural crops and ornamentals. Data concerning DM-acute genotoxicity are controversial and knowledge on its delayed effect is limited. For this reason, we aimed to further explore DM genotoxicity resulting from subchronic intoxication of experimental mice. Thus, DM was administered to mice at doses ranging from 1 to 30 mg/kg body weight for a period of 30 consecutive days. There was a significant increase (P < .05) in the frequency of micronucleated bone marrow cells following DM administration. Furthermore, the chromosome aberration assay revealed a significant increase in the percentage of chromosome abnormalities in a dose-dependent manner. Dimethoate was also found to induce significant DNA damage in mouse bone marrow cells as assessed by the comet assay. Altogether, our results showed that, after a subchronic exposure, DM was a genotoxic compound in experimental mice.

  8. Lanthanum nitrate genotoxicity evaluation: Ames test, mouse micronucleus assay, and chromosome aberration test.

    Science.gov (United States)

    Yang, Hui; Zhang, Xiaopeng; Liu, Haibo; Cui, Wenming; Zhang, Qiannan; Li, Yongning; Yu, Zhou; Jia, Xudong

    2016-11-01

    The increasing use of rare-earth elements (REE) and their compounds has led to their accumulation in the environment and has raised concern about their safety. The toxic effects of REE such as lanthanum are largely unknown; genotoxicity studies have been limited and results are controversial. We evaluated the genotoxicity of lanthanum nitrate (La(NO3)3) in several in vitro and in vivo tests, including bacterial reverse mutation assay (Ames test), mouse bone marrow micronucleus assay, and chromosome aberration assay. La(NO3)3 was not mutagenic in the Ames test. La(NO3)3 did not increase the frequencies of bone marrow micronuclei or chromosome aberration in the mouse after repeated treatments at oral doses up to 735 (females) and 855mg/kg (males). The compound did not increase the frequency of chromosome aberrations in CHO cells in vitro. These results indicate that lanthanum is not a genotoxic hazard.

  9. The micronucleus test-most widely used in vivo genotoxicity test.

    Science.gov (United States)

    Hayashi, Makoto

    2016-01-01

    Genotoxicity is commonly evaluated during the chemical safety assessment together with other toxicological endpoints. The micronucleus test is always included in many genotoxic test guidelines for long time in many classes of chemicals, e.g., pharmaceutical chemicals, agricultural chemicals, food additives. Although the trend of the safety assessment of chemicals faces to animal welfare and in vitro systems are more welcome than the in vivo systems, the in vivo test systems are paid more attention in the field of genotoxicity because of its weight of evidence. In this review, I will summarize the following points: 1) historical consideration of the test development, 2) characteristics of the test including advantages and limitations, 3) new approaches considering to the animal welfare.

  10. Genotoxic effect of Lythrum salicaria extract determined by the mussel micronucleus test.

    Science.gov (United States)

    Eck-Varanka, Bettina; Kováts, Nóra; Hubai, Katalin; Paulovits, Gábor; Ferincz, Árpád; Horváth, Eszter

    2015-12-01

    A wide range of aquatic plants have been proven to release allelochemicals, of them phenolics and tannin are considered rather widely distributed. Tannins, however, have been demonstrated to have genotoxic capacity. In our study genotoxic potential of Lythrum salicaria L. (Purple Loosestrife, family Lythraceae) was assessed by the mussel micronucleus test, using Unio pictorum. In parallel, total and hydrolysable tannin contents were determined. Results clearly show that the extract had a high hydrolysable tannin content and significant mutagenic effect. As L. salicaria has been long used in traditional medicine for chronic diarrhoea, dysentery, leucorrhoea and blood-spitting, genotoxic potential of the plant should be evaluated not only with regard to potential effects in the aquatic ecosystem, but also assessing its safe use as a medicinal herb.

  11. Assessment of genotoxic effects of flumorph by the comet assay in mice organs.

    Science.gov (United States)

    Zhang, T; Zhao, Q; Zhang, Y; Ning, J

    2014-03-01

    The present study investigated the genotoxic effects of flumorph in various organs (brain, liver, spleen, kidney and sperm) of mice. The DNA damage, measured as comet tail length (µm), was determined using the alkaline comet assay. The comet assay is a sensitive assay for the detection of genotoxicity caused by flumorph using mice as a model. Statistically significant increases in comet assay for both dose-dependent and duration-dependent DNA damage were observed in all the organs assessed. The organs exhibited the maximum DNA damage in 96 h at 54 mg/kg body weight. Brain showed maximum DNA damage followed by spleen > kidney > liver > sperm. Our data demonstrated that flumorph had induced systemic genotoxicity in mammals as it caused DNA damage in all tested vital organs, especially in brain and spleen.

  12. 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.

  13. Toward a definition of colonic inertia

    Institute of Scientific and Technical Information of China (English)

    Gabrio Bassotti; Giuseppe de Roberto; Luca Sediari; Antonio Morelli

    2004-01-01

    Chronic constipation is a relatively frequent symptom; among its subtypes, the so called-colonic inertia represents a disease condition that is often considered for surgery. However, to date, there has been no agreement on definition of colonic inertia, and a literature review showed that this definition was given to numerous entities that differ from each other.In this paper these concepts are reviewed and a more stringent definition of colonic inertia is proposed.

  14. Comparative assessment of genotoxicity of mineral water packed in polyethylene terephthalate (PET) and glass bottles.

    Science.gov (United States)

    Ceretti, Elisabetta; Zani, Claudia; Zerbini, Ilaria; Guzzella, Licia; Scaglia, Mauro; Berna, Vanda; Donato, Francesco; Monarca, Silvano; Feretti, Donatella

    2010-03-01

    The potential migration of genotoxic compounds into mineral water stored in polyethylene terephthalate (PET) bottles was evaluated by an integrated chemical/biological approach using short-term toxicity/genotoxicity tests and chemical analysis. Six commercial brands of still and carbonated mineral water bottled in PET and in glass were stored at 40 degrees C for 10 days in a stove according to the standard EEC total migration test (82/711/EEC), or at room temperature in the dark. After treatment, the samples were analysed using gas-chromatography/mass spectrometry (GC/MS) to detect volatile and non-volatile compounds, the Microtox test to evaluate potential toxicity of the samples, and three mutagenicity tests -Tradescantia and Allium cepa micronucleus tests and the Comet assay on human leukocytes - to detect their genotoxic activity. GC/MS analysis did not detect phthalates or acetaldehyde in the water samples. The Microtox test found no toxic effects. Mutagenicity tests detected genotoxic properties of some samples in both PET and glass bottles. Statistical analyses showed a positive association between mineral content and mutagenicity (micronuclei in A. cepa and DNA damage in human leukocytes). No clear effect of treatment and PET bottle was found. These results suggest the absence of toxic compounds migrating from PET regardless of time and conditions of storage. In conclusion, bottle material and stove treatment were not associated with the genotoxic properties of the water; the genotoxic effects detected in bottled water may be related to the characteristics of the water (minerals and CO(2) content).

  15. Genotoxicity of metal oxide nanomaterials: review of recent data and discussion of possible mechanisms

    Science.gov (United States)

    Golbamaki, Nazanin; Rasulev, Bakhtiyor; Cassano, Antonio; Marchese Robinson, Richard L.; Benfenati, Emilio; Leszczynski, Jerzy; Cronin, Mark T. D.

    2015-01-01

    Nanotechnology has rapidly entered into human society, revolutionized many areas, including technology, medicine and cosmetics. This progress is due to the many valuable and unique properties that nanomaterials possess. In turn, these properties might become an issue of concern when considering potentially uncontrolled release to the environment. The rapid development of new nanomaterials thus raises questions about their impact on the environment and human health. This review focuses on the potential of nanomaterials to cause genotoxicity and summarizes recent genotoxicity studies on metal oxide/silica nanomaterials. Though the number of genotoxicity studies on metal oxide/silica nanomaterials is still limited, this endpoint has recently received more attention for nanomaterials, and the number of related publications has increased. An analysis of these peer reviewed publications over nearly two decades shows that the test most employed to evaluate the genotoxicity of these nanomaterials is the comet assay, followed by micronucleus, Ames and chromosome aberration tests. Based on the data studied, we concluded that in the majority of the publications analysed in this review, the metal oxide (or silica) nanoparticles of the same core chemical composition did not show different genotoxicity study calls (i.e. positive or negative) in the same test, although some results are inconsistent and need to be confirmed by additional experiments. Where the results are conflicting, it may be due to the following reasons: (1) variation in size of the nanoparticles; (2) variations in size distribution; (3) various purities of nanomaterials; (4) variation in surface areas for nanomaterials with the same average size; (5) differences in coatings; (6) differences in crystal structures of the same types of nanomaterials; (7) differences in size of aggregates in solution/media; (8) differences in assays; (9) different concentrations of nanomaterials in assay tests. Indeed, due to the

  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. Chlorination of tramadol: Reaction kinetics, mechanism and genotoxicity evaluation.

    Science.gov (United States)

    Cheng, Hanyang; Song, Dean; Chang, Yangyang; Liu, Huijuan; Qu, Jiuhui

    2015-12-01

    Tramadol (TRA) is one of the most detected analgesics in environmental matrices, and it is of high significance to study the reactivity of TRA during chlorination considering its potential toxicity to the environment. The chlorine/TRA reaction is first order with respect to the TRA concentration, and a combination of first-order and second-order with respect to chlorine concentration. The pH dependence of the observed rate constants (kobs) showed that the TRA oxidation reactivity increased with increasing pH. kobs can be quantitatively described by considering all active species including Cl2, Cl2O and HOCl, and the individual rate constants of HOCl/TRA(0), HOCl/TRAH(+), Cl2/TRA and Cl2O/TRA reactions were calculated to be (2.61±0.29)×10(3)M(-1)s(-1), 14.73±4.17M(-1)s(-1), (3.93±0.34)×10(5)M(-1)s(-1) and (5.66±1.83)×10(6)M(-1)s(-1), respectively. Eleven degradation products were detected with UPLC-Q-TOF-MS, and the corresponding structures of eight products found under various pH conditions were proposed. The amine group was proposed to be the initial attack site under alkaline pH conditions, where reaction of the deprotonated amine group with HOCl is favorable. Under acidic and neutral pH conditions, however, two possible reaction pathways were proposed. One is an electrophilic substitution on the aromatic ring, and another is an electrophilic substitution on the nitrogen, leading to an N-chlorinated intermediate, which can be further oxidized. Finally, the SOS/umu test showed that the genotoxicity of TRA chlorination products increased with increasing dosage of chlorine, which was mostly attributed to the formation of some chlorine substitution products.

  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. Vinyl acetate monomer (VAM) genotoxicity profile: relevance for carcinogenicity.

    Science.gov (United States)

    Albertini, Richard J

    2013-09-01

    Vinyl acetate monomer (VAM) is a site-of-contact carcinogen in rodents. It is also DNA reactive and mutagenic, but only after its carboxylesterase mediated conversion to acetaldehyde (AA), a metabolic reaction that also produces acetic acid and protons. As VAM's mutagenic metabolite, AA is normally produced endogenously; detoxification by aldehyde dehydrogenase (ALDH) is required to maintain intra-cellular AA homeostasis. This review examines VAM's overall genotoxicity, which is due to and limited by AA, and the processes leading to mutation induction. VAM and AA have both been universally negative in mutation studies in bacteria but both have tested positive in several in vitro studies in higher organisms that usually employed high concentrations of test agents. Recently however, in vitro studies evaluating submillimolar concentrations of VAM or AA have shown threshold dose-responses for mutagenicity in human cultured cells. Neither VAM nor AA induced systemic mutagenicity in in vivo studies in metabolically competent mice when tested at non-lethal doses while treatments of animals deficient in aldehyde dehydrogenase (Aldh in animals) did induce both gene and chromosome level mutations. The results of several studies have reinforced the critical role for aldehyde dehydrogenase 2 (ALDH2 in humans) in limiting AA's (and therefore VAM's) mutagenicity. The overall aim of this review of VAM's mutagenic potential through its AA metabolite is to propose a mode of action (MOA) for VAM's site-of-contact carcinogenesis that incorporates the overall process of mutation induction that includes both background mutations due to endogenous AA and those resulting from exogenous exposures.

  20. Intestinal spirochetosis and colon diverticulosis

    Directory of Open Access Journals (Sweden)

    Lima Marcus Aurelho de

    2005-01-01

    Full Text Available A case of intestinal spirochetosis in a 62-year-old white male is reported. The condition was characterized by chronic flatulence and episodes of intestinal hemorrhage, in addition to the evidence of hypotonic diverticular disease, with a large number of slender organisms in the colon epithelium and cryptae. Spirochetes were demonstrated by Whartin-Starry stain. The serologic tests for syphilis and HIV were positive. Spirochetosis was treated with penicillin G, and the patient remains free of intestinal complaints 20 months later.

  1. Muscarinic Receptor Signaling in Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rosenvinge, Erik C. von, E-mail: evonrose@medicine.umaryland.edu; Raufman, Jean-Pierre [University of Maryland School of Medicine, Division of Gastroenterology & Hepatology, 22 S. Greene Street, N3W62, Baltimore, MD 21201 (United States); Department of Veterans Affairs, VA Maryland Health Care System, 10 North Greene Street, Baltimore, MD 21201 (United States)

    2011-03-02

    According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

  2. Muscarinic Receptor Signaling in Colon Cancer

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Raufman

    2011-03-01

    Full Text Available According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

  3. [Genotoxicity of drinking water during chlorine and chloramine disinfection and the influence of disinfection conditions using the umu-test].

    Science.gov (United States)

    Liu, Qing; Zhang, Li-Ping; Liu, Wen-Jun; Nie, Xue-Biao; Zhang, Su-Xia; Zhang, Shun

    2010-01-01

    In this study, the effects of disinfectant dosage, reaction time and the ratio of Cl2 to N of disinfectant on genotoxicity of effluent of ozone-biological activated carbon (O3-BAC) during chlorine or chloramine disinfection were investigated using umu-test. It was found that, the genotoxicity of effluent of O3-BAC before disinfection ranged from 20-70 ng/L, and it increased after disinfection by chlorine or chloramines. With the same reaction time(24 h), genotoxicity after chlorination (40-95 ng/L) was higher than that after chloramination (20-40 ng/L) under same initial dosage. For chlorination, with initial dosage increasing from 0 mg/L to 10 mg/L, genotoxicity increased firstly, and got the maximum value at about 0.5-1 mg/L dosage, then decreased and got the minimum value at about 3-5 mg/L dosage, and finally increased again. For chloramination, genotoxicity didn't change that much. With the dosage of 3 mg/L and reaction time increasing from 0 h to 72 h, no matter for chlorine or chloramines disinfection, genotoxicity of effluent of O3-BAC both increased firstly, and got the maximum value at about 2 h, then decreased and got the minimum value at about 18 h, and finally increased again, and genotoxicity after chlorine disinfection (83-120 ng/L) was higher than that after chloramines disinfection (20-62 ng/L) under same reaction time. Further more, effects of the different ratios of Cl2 to N of disinfectant on genotoxicity of effluent of O3-BAC were also studied. Results of this study demonstrate that under test conditions, chloramine disinfection is safer than chlorine disinfection in the aspect of genotoxicity for drinking water, and the changes of genotoxicity are different from those of total HAAs.

  4. Genotoxic activity in vivo of the naturally occurring glucoside, cycasin, in the Drosophila wing spot test.

    Science.gov (United States)

    Kawai, K; Furukawa, H; Hirono, I

    1995-03-01

    Cycasin, methylazoxymethanol-beta-glucoside, is a naturally occurring carcinogenic compound. The genotoxicity of cycasin was assayed in the Drosophila wing spot test. Cycasin induced small single and large single spots on feeding at 10 mumol/g medium. The presence of these spots indicates that cycasin is genotoxic in Drosophila melanogaster. Microorganisms which showed beta-glucosidase activity for cleaving cycasin to toxic aglycon were isolated from gut flora of the Drosophila larvae. Consequently, the Drosophila wing spot test would be useful for mutagenicity screening of other naturally occurring glucosides.

  5. Genotoxicity of the boldine aporphine alkaloid in prokaryotic and eukaryotic organisms.

    Science.gov (United States)

    Moreno, P R; Vargas, V M; Andrade, H H; Henriques, A T; Henriques, J A

    1991-06-01

    The aporphine alkaloid boldine, present in Peumus boldus (boldo-do-Chile) widely used all over the world, was tested for the presence of genotoxic, mutagenic and recombinogenic activities in microorganisms. This alkaloid did not show genotoxic activity with or without metabolic activation in the SOS chromotest and Ames tester strains TA100, TA98 and TA102. It was not able to induce point and frameshift mutations in haploid Saccharomyces cerevisiae cells. However, mitotic recombinational events such as crossing-over and gene conversion were weakly induced in diploid yeast cells by this alkaloid. Also, boldine was able to induce weakly cytoplasmic 'petite' mutation in haploid yeast cells.

  6. Genotoxic effects of boric acid and borax in zebrafish, Danio rerio using alkaline comet assay

    OpenAIRE

    Gülsoy, Nagihan; Yavaş, Cüneyd; Mutlu, Özal

    2015-01-01

    The present study is conducted to determine the potential mechanisms of Boron compounds, boric acid (BA) and borax (BX), on genotoxicity of zebrafish Danio rerio for 24, 48, 72 and 96-hours acute exposure (level:1, 4, 16, 64 mg/l BA and BX) in semi-static bioassay experiment. For that purpose, peripheral erythrocytes were drawn from caudal vein and Comet assay was applied to assess genotoxicity. Acute (96 hours) exposure and high concentrations of boric acid and borax increases % tail DNA and...

  7. Genotoxic effects of the insecticide cypermethrin on the root meristem cells of sunflowers (Helianthus annuus L.).

    Science.gov (United States)

    Inceer, Huseyin; Hayirlioglu-Ayaz, Sema; Ozcan, Melahat

    2009-11-01

    In this study, the genotoxic effects of the insecticide cypermethrin on the root meristem cells of sunflowers (Helianthus annuus L.) were investigated. The roots were treated with 10- 25- 50- and 100-ppm concentrations of cypermethrin for 6, 12 and 24 h. The mitotic index and mitotic abnormalities were determined in both control and test groups. The cypermethrin showed a marked mitodepressive action on mitosis. The types of mitotic abnormalities included disturbed metaphase, c-mitosis, stickiness, laggards and chromatid bridges. A pronounced toxic effect was observed at the 50-ppm concentration. Cypermethrin may have genotoxic effects on sunflowers.

  8. Primary lymphoma of the colon Linfoma primario de colon

    Directory of Open Access Journals (Sweden)

    Marta Pascual

    2013-02-01

    Full Text Available Background: primary colorectal lymphoma is a very rare disease, representing less than 0.5 % of all primary colorectal neoplasms. The gastrointestinal tract is the most frequently involved site of all extranodal lymphomas, the most common type of that is non-Hodgkin's lymphoma. Early diagnosis is often difficult because of unspecific symptoms. Therapeutic approaches have classically included radical resection, chemotherapy and radiotherapy. Materials and methods: we present our experience in the management of primary colorectal lymphomas over a 17-year period (1994-20011. Results: in this period 7 cases of primary colorectal lymphoma were diagnosed in our institution. Abdominal pain and change in bowel habit were the most frequent symptoms. Five patients underwent emergency surgery because of bleeding or bowel obstruction. All primary intestinal lymphomas studied were of the B-cell phenotype. Patients were followed up for a median of 59 months (range 1-180. Three of them are alive with no evidence of recurrence. Conclusion: combination treatment with chemotherapy and surgery can obtain good remission rate. Surgery can resolve complications such bleeding or intestinal perforation that are implicated in lymphoma mortality.Introducción: el linfoma primario de colon y recto es una patología poco prevalente, representa tan solo el 0,5 % de todas las neoplasias primarias de colon y recto. El tracto gastrointestinal es el lugar donde asientan la gran mayoría de los linfomas extranodales, siendo el más frecuente el tipo linfoma no-Hodking. El diagnóstico precoz es siempre difícil debido a que la sintomatología es muy poco específica. Los algoritmos terapéuticos han incluido clásicamente la resección radical, el tratamiento con quimioterapia y con radioterapia. Materiales y métodos: presentamos nuestra experiencia en el manejo de los linfomas primarios de colon en un periodo de 17 años (1994-2011. Resultados: en dicho periodo en nuestro

  9. 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

  10. Imaging of total colonic Hirschsprung disease

    Energy Technology Data Exchange (ETDEWEB)

    Stranzinger, Enno; DiPietro, Michael A.; Strouse, Peter J. [University of Michigan Health System, Section of Pediatric Radiology, Ann Arbor, MI (United States); Teitelbaum, Daniel H. [University of Michigan Health System, Section of Pediatric Surgery, Ann Arbor, MI (United States)

    2008-11-15

    Hirschsprung disease (HD) is a functional obstruction of the bowel caused by the absence of intrinsic enteric ganglion cells. The diagnosis of total colonic HD (TCHD) based on contrast enemas is difficult in newborns because radiological findings vary. To evaluate the radiographic and contrast enema findings in patients with pathologically proven TCHD. From 1966 to 2007, 17 records from a total of 31 patients with TCHD were retrospectively evaluated for diameter and shape of the colon, diameter of the small bowel, bowel wall contour, ileal reflux, abdominal calcifications, pneumoperitoneum, filling defects, transitional zones and rectosigmoid index. Three colonic patterns of TCHD were found: microcolon, question-mark-shape colon and normal caliber colon. Additional findings included spasmodic colon, ileal reflux, delayed evacuation and abdominal calcifications. Colonic transitional zones were found in eight patients with TCHD. The diagnosis of TCHD is difficult to establish by contrast enema studies. The length of the aganglionic small bowel and the age of the patient can influence the radiological findings in TCHD. The transitional zone and the rectosigmoid index can be false-positive in TCHD. The colon can appear normal. Consider TCHD if the contrast enema study is normal but the patient remains symptomatic and other causes of distal bowel obstruction have been excluded. (orig.)

  11. Inguinal lymph node metastasis of colon cancer

    Directory of Open Access Journals (Sweden)

    Sloane McGraw

    2011-01-01

    Full Text Available We present a case of adenocarcinoma of colon with unusual metastasis to inguinal lymph nodes. Our patient is a young male with bilateral inguinal lymphadenopathy, bone pains, and jaundice who presented as carcinoma of unknown primary. He was diagnosed as widely metastatic adenocarcinoma of colon for which he received chemotherapy and has had a good response to the treatment.

  12. Incidence of retrorenal colon during percutaneous nephrolithotomy

    Directory of Open Access Journals (Sweden)

    Mehmet Balasar

    2015-04-01

    Full Text Available Objective The aim of this study was to investigate retrorenal colon incidence in percutaneous nephrolithotomy (PNL interventions made in our clinic. Materials and Methods Clinical data of 804 PNL patients, accumulated over a 7 year period (2006-2012, was surveyed. The patient files were reviewed retrospectively, and only those who had abdominal computed tomography (CT images before PNL intervention were included in the study. In the CT images, the position of both the ascending and descending colon in relation to the right and left kidneys were evaluated. Results According to our hospital reports, 394 patients with CT images were included in the present study 27 patients (6.9% had retrorenal colon, of which 18 (4.6% were on the left side, 4 (1.0% on the right side and 5 (1.3% had bilateral retrorenal colons. Colonic perforation complication was seen only in two patients and the colonic perforation rate was 0.3%. These two cases had no CT images. Conclusions PNL, in the process of becoming the standard treatment modality, is a safe and reliable technique for renal stone treatment. Colonic injury should be taken into consideration during PNL interventions of the lower pole of the kidney (especially on the left side due to the location of retrorenal colon.

  13. The colon shuffle : A modified urinary diversion

    NARCIS (Netherlands)

    Meijer, R. P.; Mertens, L. S.; Meinhardt, W.; Verwaal, V. J.; Dik, P.; Horenblas, S.

    2015-01-01

    Aim To assess the results of a urinary diversion in patients who already have a colostomy or simultaneously require a (rectum) colon resection. The diversion is created from the distal part of the transected colon with a simultaneously created new colostomy contra-laterally (if necessary). This proc

  14. Reversible projection technique for colon unfolding.

    Science.gov (United States)

    Yao, Jianhua; Chowdhury, Ananda S; Aman, Javed; Summers, Ronald M

    2010-12-01

    Colon unfolding provides an efficient way to navigate the colon in computed tomographic colonography (CTC). Most existing unfolding techniques only compute forward projections. When radiologists find abnormalities or conduct measurements on the unfolded view (which is often quicker and easier), it is difficult to locate the corresponding region on the 3-D view for further examination (which is more accurate and reliable). To address this, we propose a reversible projection technique for colon unfolding. The method makes use of advanced algorithms including rotation-minimizing frames, recursive ring sets, mesh skinning, and cylindrical projection. Both forward and reverse mapping can be computed for points on the colon surface. Therefore, it allows for detecting and measuring polyps on the unfolded view and mapping them back to the 3-D surface. We generated realistic colon simulation data incorporating most colon characteristics, such as curved centerline, variable distention, haustral folds, teniae coli, and colonic polyps. Our method was tested on both simulated data and data from 110 clinical CTC studies. The results showed submillimeter accuracy in simulated data and -0.23 ± 1.67 mm in the polyp measurement using clinical CTC data. The major contributions of our technique are: 1) the use of a recursive ring set method to solve the centerline and surface correspondence problem; 2) reverse transformation from the unfolded view to the 3-D view; and 3) quantitative validation using a realistic colon simulation and clinical CTC polyp measurement.

  15. Immunosurveillance against tetraploidization-induced colon tumorigenesis

    NARCIS (Netherlands)

    Boileve, A.; Senovilla, L.; Vitale, I.; Lissa, D.; Martins, I.; Metivier, D.; van den Brink, S.; Clevers, H.; Galluzzi, L.; Castedo, M.; Kroemer, G.

    2013-01-01

    Circumstantial evidence suggests that colon carcinogenesis can ensue the transient tetraploidization of (pre-)malignant cells. In line with this notion, the tumor suppressors APC and TP53, both of which are frequently inactivated in colon cancer, inhibit tetraploidization in vitro and in vivo. Here,

  16. Adenosquamous Carcinoma of Colon and Rectum

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@ In colon and rectum, adenosquamous carcinoma is extremely rare. 6 patients with adenosquamous carcinoma of colon and rectum were identified by Tianjin Medical University Cancer Hospital from Jan. 1967 to Dec. 1997. 2 male and 4 female had a median age of 48 (range, 40- 60) years. All patients were treated surgically.

  17. Evaluation of occupational genotoxic risk in a Brazilian hospital

    Directory of Open Access Journals (Sweden)

    Sharbel Weidner Maluf

    2000-06-01

    Full Text Available 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 cytochalasin-blocked lymphocytes with micronuclei, though it was not significant (P = 0.058. The groups exposed to antineoplastic drugs and radiation had a significant increase in micronuclei frequency (P = 0.038 and P = 0.022, respectively. The high frequencies of dicentric bridges suggest the action of clastogenics in these two groups. These results suggest that the safety procedures adopted were very important to protect workers from exposure to mutagenic agents and should be improved in the radiological and chemotherapeutical areas.Vários procedimentos terapêuticos, diagnósticos e profiláticos usados em hospitais apresentam um risco genético. Para avaliar o risco genotóxico ocupacional, 42 trabalhadores do Hospital de Clínicas de Porto Alegre, RS, Brasil, ocupacionalmente expostos a chumbo (uso de soldas, óxido de etileno (área de esterilização, drogas antineoplásicas (enfermeiros e farmacêuticos e radiação ionizante foram comparados com 42 indivíduos não expostos. A análise de linfócitos binucleados apresentou um aumento estatisticamente não significativo (P = 0.058 na freqüência de micronúcleos. Quando analisados separadamente, os grupos expostos a drogas antineoplásicas e radiação ionizante apresentaram um aumento estatisticamente significativo (P = 0.038 e P = 0.0217, respectivamente na freqüência de micronúcleos. As freqüências de pontes dicêntricas e anomalias de fuso sugerem a ação de clastogênicos nestes dois

  18. 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

  19. Evolution of phenotypic plasticity in colonizing species.

    Science.gov (United States)

    Lande, Russell

    2015-05-01

    I elaborate an hypothesis to explain inconsistent empirical findings comparing phenotypic plasticity in colonizing populations or species with plasticity from their native or ancestral range. Quantitative genetic theory on the evolution of plasticity reveals that colonization of a novel environment can cause a transient increase in plasticity: a rapid initial increase in plasticity accelerates evolution of a new optimal phenotype, followed by slow genetic assimilation of the new phenotype and reduction of plasticity. An association of colonization with increased plasticity depends on the difference in the optimal phenotype between ancestral and colonized environments, the difference in mean, variance and predictability of the environment, the cost of plasticity, and the time elapsed since colonization. The relative importance of these parameters depends on whether a phenotypic character develops by one-shot plasticity to a constant adult phenotype or by labile plasticity involving continuous and reversible development throughout adult life.

  20. Duplication Cyst of the Sigmoid Colon

    Directory of Open Access Journals (Sweden)

    Bastian Domajnko

    2009-01-01

    Full Text Available A 21-year-old male with developmental delay presented with abdominal pain of two days' duration. He was afebrile and his abdomen was soft with mild diffuse tenderness. There were no peritoneal signs. Plain x-ray demonstrated a large air-filled structure in the right upper quadrant. Computed tomography of the abdomen revealed a 9×8 cm structure adjacent to the hepatic flexure containing an air-fluid level. It did not contain oral contrast and had no apparent communication with the colon. At operation, the cystic lesion was identified as a duplication cyst of the sigmoid colon that was adherent to the right upper quadrant. The cyst was excised with a segment of the sigmoid colon and a stapled colo-colostomy was performed. Recovery was uneventful. Final pathology was consistent with a duplication cyst of the sigmoid colon. The cyst was attached to the colon but did not communicate with the lumen.

  1. Analysis of positions and substituents on genotoxicity of fluoroquinolones with quantitative structure-activity relationship and 3D Pharmacophore model.

    Science.gov (United States)

    Fengxian, Chen; Reti, Hai

    2017-02-01

    The genotoxicity values of 21 quinolones were studied to establish a quantitative structure-activity relationship model and 3D Pharmacophore model separately for screening essential positions and substituents that contribute to genotoxicity of fluoroquinolones (FQs). A full factor experimental design was performed to analyze the specific main effect and second-order interaction effect of different positions and substituents on genotoxicity, forming a reasonable modification scheme which was validated on typical FQ with genotoxicity and efficacy data. Four positions (1, 5, 7, 8) were screened finally to form the full factorial experimental design which contained 72 congeners in total, illustrating that: the dominant effect of 5 and 7-positions on genotoxicity of FQs is main effect; meanwhile the effect of 1 and 8-positions is a second-order interaction effect; two adjacent positions always have stronger second-order interaction effect and lower genotoxicity; the obtained modification scheme had been validated on typical FQ congeners with the modified compound has a lower genotoxicity, higher synthesis feasibilities and efficacy.

  2. Change in genotoxicity of wastewater during chlorine dioxide and chlorine disinfections and the influence of ammonia nitrogen

    Institute of Scientific and Technical Information of China (English)

    WANG Lisha; HU Hongying; WANG Chao; Koichi Fujie

    2007-01-01

    The effects of chlorine dioxide and chlorine disinfections on the genotoxicity of different biologically treated sewage wastewater samples were studied by umu-test.The experiment results showed that when chlorine dioxide dosage was increased from 0 to 30 mg/L,the genotoxicity of wastewater first decreased rapidly and then tended to be stable,while when the chlorine dosage was increased from 0 to 30 mg/L,the genotoxicity of wastewater changed diversely for different samples.It was then found that ammonia nitrogen did not affect the change of genotoxicity during chlorine dioxide disinfection of wastewater,while it greatly affected the change of genotoxicity during chlorine disinfection of wastewater.When the concentration of ammonia nitrogen was low(<10-20mg/L),the genotoxicity of wastewater decreased after chlorine disinfection,and when the concentration of ammonia nitrogen was high(>10-20 mg/L),the genotoxicity of wastewater increased after chlorine disinfection.

  3. Evaluation of genotoxicity using automated detection of γH2AX in metabolically competent HepaRG cells.

    Science.gov (United States)

    Quesnot, Nicolas; Rondel, Karine; Audebert, Marc; Martinais, Sophie; Glaise, Denise; Morel, Fabrice; Loyer, Pascal; Robin, Marie-Anne

    2016-01-01

    The in situ detection of γH2AX was recently reported to be a promising biomarker of genotoxicity. In addition, the human HepaRG hepatoma cells appear to be relevant for investigating hepatic genotoxicity since they express most of drug metabolizing enzymes and a wild type p53. The aim of this study was to determine whether the automated in situ detection of γH2AX positive HepaRG cells could be relevant for evaluation of genotoxicity after single or long-term repeated in vitro exposure compared to micronucleus assay. Metabolically competent HepaRG cells were treated daily with environmental contaminants and genotoxicity was evaluated after 1, 7 and 14 days. Using these cells, we confirmed the genotoxicity of aflatoxin B1 and benzo(a)pyrene and demonstrated that dimethylbenzanthracene, fipronil and endosulfan previously found genotoxic with comet or micronucleus assays also induced γH2AX phosphorylation. Furthermore, we showed that fluoranthene and bisphenol A induced γH2AX while no effect had been previously reported in HepG2 cells. In addition, induction of γH2AX was observed with some compounds only after 7 days, highlighting the importance of studying long-term effects of low doses of contaminants. Together, our data demonstrate that automated γH2AX detection in metabolically competent HepaRG cells is a suitable high-through put genotoxicity screening assay.

  4. "Cat scratch colon" in a patient with ischemic colitis.

    Science.gov (United States)

    Park, Eui Ju; Lee, Joon Seong; Lee, Tae Hee; Choi, Dae Han; Kim, Eui Bae; Jeon, Seong Ran; Hong, Su Jin; Kim, Jin-Oh

    2015-03-01

    "Cat scratch colon" is a gross finding characterized by hemorrhagic mucosal scratches on colonoscopy. It is usually associated with a normal colon and is rarely associated with collagenous colitis. In a previous report, cat scratch colon was noted in the cecum and ascending colon, but has also been observed in the distal transverse colon. The patient in this study was also diagnosed with ischemic colitis that may have played a role in the development of cat scratch colon.

  5. 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.

  6. Snakehead-fish cell line, SSN-1 (Ophicephalus striatus) as a model for cadmium genotoxicity testing.

    Science.gov (United States)

    Aramphongphan, A; Laovitthayanggoon, S; Himakoun, L

    2009-08-01

    The purpose of this study is to evaluate the potential of snakehead-fish cell line (SSN-1 cells) derived from a striped snakehead (Ophicephalus striatus) as a model in the genotoxic assessment of cadmium (Cd). The first approach employed was to determine the contaminated Cd levels in commercial snakehead fish by the Graphite Atomic Absorption Spectrophotometer. In the second approach, the sensitivity of SSN-1 cells to cytotoxicity and genotoxicity of Cd was assessed by Trypan blue and micronucleus assays following 24, 48, and 72 h of incubation period. Exposure of SSN-1 cells to four increasing Cd concentrations ranging from 0.005 to 5 ppm for 72 h did not affect their survival as compared to the control cells. The Cd uptake by SSN-1 cells showed a concentration-dependent increase in intracellular Cd levels. Three non-cytotoxic Cd concentrations (0.05, 0.5, and 5 ppm) showed a concentration-dependent genotoxic effect, compared to relevant control cells. Both micronucleus frequencies and cadmium uptake levels by SSN-1 cells depended on exposure concentrations. These results showed that the SSN-1 cells are suitable for use as a model for in vitro Cd genotoxicity testing.

  7. 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...

  8. Genotoxicity of rice bran oil extracted by supercritical CO2 extraction.

    Science.gov (United States)

    Choi, Jae-Suk; Cheon, Eun Jin; Kim, Tae-Uk; Moon, Woi-Sook; Kim, Joo-Wan; Kim, Mi-Ryung

    2014-01-01

    Rice bran oil extracted by supercritical CO2 extraction (RB-SCE) reportedly exhibits pharmacological activities such as antioxidant and in vivo hair growth-inducing effects. Such activities raise the possibility of the development of novel hair growth-inducing agents using RB-SCE. The aim of this study was to investigate the potential genotoxic effects of RB-SCE in three short-term mutagenicity assays (bacterial reverse mutation assay, in vitro mammalian chromosomal aberration test, and in vivo micronucleus assay). RB-SCE showed no genotoxicity in the bacterial reverse mutation assay up to 5000 mg/plate and in the in vivo micronucleus test up to 600 mg/kg body weight. However, at 120 µg/mL with S9 mix and 200 µg/mL without S9 mix RB-SCE showed significantly different genotoxicity than the negative control in the in vitro chromosome aberration test. The induction of chromosomal aberrations under the present conditions may have no biological significance. We have herein demonstrated that RB-SCE can be regarded as a non-genotoxic material based on the available in vivo and in vitro results.

  9. Potentially harmful elements in house dust from Estarreja, Portugal: characterization and genotoxicity of the bioaccessible fraction.

    Science.gov (United States)

    Plumejeaud, Sophie; Reis, Amelia Paula; Tassistro, Virginie; Patinha, Carla; Noack, Yves; Orsière, Thierry

    2016-10-22

    Due to their behavioral characteristics, young children are vulnerable to the ingestion of indoor dust, often contaminated with chemicals that are potentially harmful. Exposure to potentially harmful elements (PHEs) is currently exacerbated by their widespread use in several industrial, agricultural, domestic and technological applications. PHEs cause adverse health effects on immune and nervous systems and can lead to cancer development via genotoxic mechanisms. The present study is an integrated approach that aims at assessing the genotoxicity of bioaccessible PHEs following ingestion of contaminated house dust. A multidisciplinary methodology associating chemical characterization of five house dust samples, extraction of the bioaccessible PHEs in gastric extracts by the unified BARGE method, determination of the bioaccessible fraction and in vitro genotoxicity of gastric extracts in adenocarcinoma gastric human (AGS) cells was developed. The five gastric extracts induced dose-dependent genotoxicity in AGS cells. Copper (bioaccessible concentration up to 111 mg/kg) was probably the prevalent PHE inducing primary DNA damage (up to 5.1-fold increase in tail DNA at 0.53 g/l of gastric extract). Lead (bioaccessible concentration up to 245 mg/kg) was the most prevalent PHE inducing chromosome-damaging effects (r = 0.55; p health risks.

  10. Genotoxic and antibutyrylcholinesterasic activities of acid violet 7 and its biodegradation products.

    Science.gov (United States)

    Mansour, Hedi Ben; Mosrati, Ridha; Limem, Ilef; Corroler, David; Ghedira, Kamel; Barillier, Daniel; Chekir-Ghedira, Leila

    2009-01-01

    Acid violet 7, a sulfonated azo dye was degraded by Pseudomonas putida mt-2 in mineral medium at concentrations up to 200 mg/L. The genotoxicity of AV7 and its biodegradation extracts was evaluated by using the DNA-strand scission assay. No genotoxicity was observed, even with or without exposition to UV irradiation, for biodegradation under shaking conditions, but increased significantly after biodegradation under static conditions. In addition, the ability of tested compounds to reduce human plasma butyrylcholinesterase (BuChE) activity was evaluated in vitro. Genotoxicity and anti-BuChE activity generated by the azoreduction products [4'-aminoacetanilid (4'-AA) and 5-acetamido-2-amino-1-hydroxy-3,6-naphtalene disulfonic acid (5-ANDS)] were assessed and compared with that of the parent unsubstituted amines. 4'-AA exhibited a strong genotoxicity, which was imputed to the presence of the acetoxy (COCH3) substituent on the aromatic amine; however, the presence of sulphonic groups in 5-ANDS seems to be responsible for its BuChE inhibition activity. The present study demonstrates that P. putida mt-2, incubated under aerobic conditions, has a catabolism that enables it to degrade AV7 and, especially, to detoxify the dye mixtures.

  11. Unravelling mechanisms of dietary flavonoid-mediated health effects: effects on lipid metabolism and genotoxicity

    NARCIS (Netherlands)

    Hoek-van den Hil, E.F.

    2015-01-01

    Summary Consumption of foods containing flavonoids is associated with a reduced risk of cardiovascular diseases (CVD), possibly by lipid-lowering effects. On the other hand, for one of these flavonoids, quercetin, also genotoxicity was shown especially in in vitro bioassays. Therefo

  12. Amethod for genotoxicity detection using random amplified polymorphism DNA with Danio rerio

    Institute of Scientific and Technical Information of China (English)

    RongZY; YinHW

    2002-01-01

    The increasing presence of genotoxic pollutants in the equatic environment has led to the development of quick monitoring methods.We have applied the random amplified polymorphism DNA(RKAPD) method to evaluate the toxic effects of genotoxic chemicals.In all 22 of normal wild type Danio rerio(zebrafish),78 amplified bands were obtained after PCR using primers set,in which the frequency of emergency above 60 percent is 21.There do exist 4 stable bands in the amplifed product,which appear in all normal test samples.The zebrafish RAPD fingerprinting database is set up on this base.The RAPD pattern from zebrafishes exposed to genotoxic chemicals such as cyclophosphamide 0.1-10mg·L-1 and dimethoate 10-100mg·L-1 displayed some changes in polymorphism of band pattern including the lost of stable bands.There also exists distinct distance between the band pattern of exposed zebrafishes and the control samples via the cluster method.In addition,the result derived from numeric analysis is more sensitive than the result obtained from stable band analysis because it can reveal the distance between the band pattern of 0.05mg·L-1 cyclophosphamide exposed zebrafish and the control sample.These results showed the accuracy and the sensitivity of the two analyses of genotoxicity based on the RAPD fingerprinting research.

  13. 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.

  14. Genotoxicity study of an experimental beverage made with quinua, kiwicha and kañiwa

    Directory of Open Access Journals (Sweden)

    Francia D.P. Huaman

    2014-12-01

    Full Text Available Genotoxic evaluation is an important step for a product that is aimed for human consumption. A beverage composed of pseudocereals with highly nutritious elements like quinua (Chenopodium quinoa Willd., kiwicha (Amaranthus caudatus L. and kañiwa (Chenopodium pallidicaule Aellen was prepared to reduce lipid contents in a group of volunteers. The objective of the present study is to evaluate the genotoxic potential of an experimental beverage using two in vitro tests that have been validated by international agencies. For the Ames test, two strains of Salmonella typhimurium (TA98 and TA100 with and without microsomal fraction (S9 were used. Four doses of the beverage were tested and also a possible protective effect (same four doses of beverage added to plates with mutagens. Cultures of binucleated lymphocytes and five doses of the beverage were used for the micronucleus test. Both Ames and the micronucleus tests showed the beverage has not genotoxic effect in all tested doses. However, in evaluating the possible protective effect of the beverage, it would be evident that on the contrary, the mutagenic effect of mutagens used for each strain is enhanced. These results suggest that additional tests should be performed to check the genotoxic potential of this beverage before consumption.

  15. In vitro analysis of the phytotoxic and genotoxic potential of Aligarh wastewater and Mathura refinery wastewater

    Directory of Open Access Journals (Sweden)

    Naveed Ahmad Fazili

    2014-01-01

    Full Text Available Present report deals with the phytotoxicity and genotoxicity of Mathura refinery wastewater and Aligarh wastewater of Northern India. The IC50 value in Allium cepa root growth inhibition test was recorded to be 0.14X and 0.10X for Mathura refinery and Aligarh industrial wastewaters, respectively. Significant decline in the survival of various Escherichia coli K12 DNA repair defective mutants was observed when the tester strains were exposed to the aforementioned samples. The order of sensitivity was invariably as: AB1157 (wild type < AB2494 (lexA mutant < AB2463 (recA mutant < AB2480 (uvrA recA double mutant. These results suggested a significant amount of DNA damage within the bacterial cells exposed to test wastewaters. A. cepa genotoxicity test also demonstrated a considerable amount of chromosomal damage of A. cepa brought about by the test samples. The aberration index (A.I. for Aligarh wastewater and refinery wastewater was recorded to be 11.2% and 14.7%, respectively, whereas the aquaguard mineral water serving as negative control displayed the A.I. value to be 2.6%. Interestingly, genotoxicity of both industrial wastewaters was reduced to a remarkable extent in presence of mannitol, the hydroxyl radical scavenger. Present study clearly indicated a distinct pattern of the chromosomal aberrations showing predominantly stickiness and stray chromosomes in case of AWW while clumping and stickiness in case of RWW, thereby affirming the genotoxicity of both test waters.

  16. Genotoxic activity and inhibition of soil respiration by ptaquiloside, a bracken fern carcinogen

    DEFF Research Database (Denmark)

    Schmidt, Bjørn; Rasmussen, L.H.; Svendsen, Gitte Winkel;

    2005-01-01

    Ptaquiloside (PTA) is a natural toxin produced by bracken (Pteridium aquilinum [L.] Kuhn). Assessment of PTA toxicity is needed because PTA deposited from bracken to soil may leach to surface and groundwater. Inhibition of soil respiration and genotoxic activity of PTA was determined by a soil mi...

  17. Formation of genotoxic compounds by medium pressure ultra violet treatment of nitrate rich water

    NARCIS (Netherlands)

    Martijn, A.J.; Boersma, M.G.; Vervoort, Jacques; Rietjens, I.; Kruithof, J.C.

    2014-01-01

    Genotoxic compounds were produced by full-scale medium pressure (MP) ultraviolet hydrogen peroxide (UV/H2O2) treatment of nitrate-rich pretreated surface water. It was hypothesized that this formation was caused by the reaction of nitrate photolysis intermediates with natural organic matter (NOM). A

  18. Genotoxicity detected in wild mice living in a highly polluted wetland area in south western Spain

    Energy Technology Data Exchange (ETDEWEB)

    Mateos, Santiago; Daza, Paula; Dominguez, Inmaculada; Cardenas, Jose Antonio [University of Seville, Department of Cell Biology, Faculty of Biology, Avenida de la Reina Mercedes no 6, E-41012 Seville (Spain); Cortes, Felipe [University of Seville, Department of Cell Biology, Faculty of Biology, Avenida de la Reina Mercedes no 6, E-41012 Seville (Spain)], E-mail: cortes@us.es

    2008-06-15

    A field study was carried out in the south of the Iberian Peninsula in an industrial area in the neighbourhood of Huelva city, SW Spain, and in a natural area (Donana National Park) for comparison, to estimate the genetic risk induced by environmental pollution in wild mice. Genotoxic effects in a sentinel organism, the Algerian mice (Mus spretus) free living in the industrial area were compared with animals of the same species living in the natural protected area. The single cell gel electrophoresis, or Comet assay, was performed as a genotoxicity test in peripheral blood of mice. Our results clearly show that mice free living in the contaminated area bear a high burden of genetic damage as compared with control individuals. The results suggest that the assessing of genotoxicity levels by the Comet assay in wild mice can be used as a valuable test in pollution monitoring and environmental conservation. - We have found an increased genotoxic damage in wild mice in a highly polluted area from industry, mining and agriculture in SW Spain, as assessed by the Comet assay.

  19. 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.

  20. 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.

  1. Formation potentials of typical DBPs and changes of genotoxicity for chlorinated tertiary effluent pretreated by ozone

    Institute of Scientific and Technical Information of China (English)

    CAO Nan; MIAO Tingting; LI Kuixiao; ZHANG Yu; YANG Min

    2009-01-01

    The effects of ozonation on the formation potential of typical disinfection byproducts (DBPs) and the changes of genotoxicity during post chlorination of tertiary effluent from a sewage treatment plant were investigated. Ozonation enhanced the yields of all detected chlorine DBPs except CHCl3. At a chlorine dose of 5 mg/L, the three brominated THMs and five HAAs increased, while chloroform decreased with the increase of ozone dose from 0 to 10 mg/L (ozone dose in consumption base). At a chlorine dose of 10 mg/L, the two mixed bromochloro species THMs and two dominant HAAs (DCAA and TCAA) firstly increased and then decreased with the increase of ozone dose, with the turning point approximately occurring at an ozone dose of 5 mg/L. The genotoxicity detected using umu test, on the other hand, was removed from 7 μg 4-NQO/L to a negligible level by ozonation under an ozone dose of 5 mg/L. Chlorination could further remove the genotoxicity to some extent. It was found that SUVA (UV absorbance divided by DOC concentration) might be used as an indicative parameter for monitoring the removal of genotoxicity during the oxidation.

  2. Genotoxicity of quinolone antibiotics in chlorination disinfection treatment: formation and QSAR simulation.

    Science.gov (United States)

    Li, Min; Wei, Dongbin; Du, Yuguo

    2016-10-01

    Lots of unexpected disinfection by-products were formed during the chlorination disinfection of contaminated water bodies, leading to a potential threat to human health and ecological safety. In this study, SOS/umu assay was used to trace the genotoxicity variation of 20 quinolone compounds during the chlorination disinfection. Furthermore, two- and three-dimensional quantitative structure-activity relationship models were developed based on the electronic and hydrophobic properties of the quinolones, which were used to quantify the impact of the different structural features of the compounds on their genotoxicity variation. The results revealed that quinolones bearing hydrophilic substituents with less H-bond donors and negative charge at the 1-position of the quinolone ring exhibited a positive correlation with genotoxicity elevation. More notably, the chlorination of quinolones in both ultrapure water and secondary effluent matrices provided comparable levels of genotoxicity, indicating that our research could potentially be used to evaluate the environmental risk of quinolone antibiotics in chlorination disinfection treatment.

  3. Induction of cytotoxic and genotoxic effects of Guandu River waters in the Allium cepa system

    Directory of Open Access Journals (Sweden)

    Jennifer Vieira Gomes

    2015-01-01

    Full Text Available The Guandu River is the main source of water supply for the metropolitan region of Rio de Janeiro and has been facing serious environmental problems due to increasing population and industrial pollution, as well as the presence of polluted tributaries. This study analyzed the cytotoxic and genotoxic potential of the Guandu River’s waters, through the use of the Allium cepa test system. Collection points were chosen at the greatest confluences of pollutant sources. The sampling included two different seasons: the rainy season (January and February and the dry season (June and July. The analyses of 5000 cells per treatment showed that all the points studied had some degree of cytotoxicity and/or genotoxicity. Two sampling locations, which receive major influxes from the polluted waters of the Poços/Queimados and Cabuçu/Ipiranga Rivers, stood out for the strong presence of micronuclei, sticky chromosomes, mitotic spindle abnormalities, necrotic cells and nucleolar changes compared to the negative control. At least two locations also found changes in the mitotic index. The existence of variations in the number of cytotoxic and genotoxic changes between periods of rain and drought indicates that the cytotoxic and genotoxic potential of the water pollutants varies according to time, depending on the discharges of the tributary rivers and the increase of contaminated effluents. The results highlight the importance of bio-monitoring to assist managers in the control of effluent discharge.

  4. Cytotoxic and genotoxic effects of two hair dyes used in the formulation of black color.

    Science.gov (United States)

    Tafurt-Cardona, Yaliana; Suares-Rocha, Paula; Fernandes, Thaís Cristina Casimiro; Marin-Morales, Maria Aparecida

    2015-12-01

    According to the International Agency for Research on Cancer (IARC), some hair dyes are considered mutagenic and carcinogenic in in vitro assays and exposed human populations. Epidemiological studies indicate that hairdressers occupationally exposed to hair dyes have a higher risk of developing bladder cancer. In Brazil, 26% of the adults use hair dye. In this study, we investigated the toxic effects of two hair dyes, Basic Red 51 (BR51) and Basic Brown 17 (BB17), which are temporary dyes of the azo group (R-N=N-R'), used in the composition of the black hair dye. To this end, MTT and trypan blue assays (cytotoxicity), comet and micronucleus assay (genotoxicity) were applied, with HepG2 cells. For cytotoxic assessment, dyes were tested in serial dilutions, being the highest concentrations those used in the commercial formula for hair dyes. For genotoxic assessment concentrations were selected according to cell viability. Results showed that both dyes induced significant cytotoxic and genotoxic effects in the cells, in concentrations much lower than those used in the commercial formula. Genotoxic effects could be related to the azo structure present in the composition of the dyes, which is known as mutagenic and carcinogenic. These results point to the hazard of the hair dye exposure to human health.

  5. Lab-on-a-chip-based high-throughput screening of the genotoxicity of engineered nanomaterials.

    Science.gov (United States)

    Vecchio, Giuseppe; Fenech, Michael; Pompa, Pier Paolo; Voelcker, Nicolas H

    2014-07-09

    The continuous increasing of engineered nanomaterials (ENMs) in our environment, their combinatorial diversity, and the associated genotoxic risks, highlight the urgent need to better define the possible toxicological effects of ENMs. In this context, we present a new high-throughput screening (HTS) platform based on the cytokinesis-block micronucleus (CBMN) assay, lab-on-chip cell sorting, and automated image analysis. This HTS platform has been successfully applied to the evaluation of the cytotoxic and genotoxic effects of silver nanoparticles (AgNPs) and silica nanoparticles (SiO2NPs). In particular, our results demonstrate the high cyto- and genotoxicity induced by AgNPs and the biocompatibility of SiO2NPs, in primary human lymphocytes. Moreover, our data reveal that the toxic effects are also dependent on size, surface coating, and surface charge. Most importantly, our HTS platform shows that AgNP-induced genotoxicity is lymphocyte sub-type dependent and is particularly pronounced in CD2+ and CD4+ cells.

  6. 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.

  7. Comprehensive DNA Adduct Analysis Reveals Pulmonary Inflammatory Response Contributes to Genotoxic Action of Magnetite Nanoparticles

    Directory of Open Access Journals (Sweden)

    Kousuke Ishino

    2015-02-01

    Full Text Available Nanosized-magnetite (MGT is widely utilized in medicinal and industrial fields; however, its toxicological properties are not well documented. In our previous report, MGT showed genotoxicity in both in vitro and in vivo assay systems, and it was suggested that inflammatory responses exist behind the genotoxicity. To further clarify mechanisms underlying the genotoxicity, a comprehensive DNA adduct (DNA adductome analysis was conducted using DNA samples derived from the lungs of mice exposed to MGT. In total, 30 and 42 types of DNA adducts were detected in the vehicle control and MGT-treated groups, respectively. Principal component analysis (PCA against a subset of DNA adducts was applied and several adducts, which are deduced to be formed by inflammation or oxidative stress, as the case of etheno-deoxycytidine (εdC, revealed higher contributions to MGT exposure. By quantitative-LC-MS/MS analysis, εdC levels were significantly higher in MGT-treated mice than those of the vehicle control. Taken together with our previous data, it is suggested that inflammatory responses might be involved in the genotoxicity induced by MGT in the lungs of mice.

  8. In Vitro and In Vivo Genotoxicity Assessment of Aristolochia manshuriensis Kom.

    Directory of Open Access Journals (Sweden)

    Youn-Hwan Hwang

    2012-01-01

    Full Text Available Arisolochiae species plants containing aristolochic acids I and II (AA I and AA II are well known to cause aristolochic acid nephropathy (AAN. Recently, there are various approaches to use AAs-containing herbs after the removal of their toxic factors. However, there is little information about genotoxicity of Arisolochiae manshuriensis Kom. (AMK per se. To obtain safety information for AMK, its genotoxicity was evaluated in accordance with OECD guideline. To evaluate genotoxicity of AMK, we tested bacterial reverse mutation assay, chromosomal aberration test, and micronucleus test. Here, we also determined the amounts of AA I and II in AMK (2.85 ± 0.08 and 0.50 ± 0.02 mg/g extract, resp.. In bacterial reverse mutation assay, AMK dose-dependently increased revertant colony numbers in TA98, TA100 and TA1537 regardless of metabolic activation. AMK increased the incidence of chromosomal aberration in Chinese hamster ovary-K1 cells, but there was no statistically significant difference. The incidences of micronucleus in bone marrow erythrocyte were significantly increased in mice after oral administration of AMK (5000 mg/kg, comparing with those of vehicle group (P<0.05. The results of three standard tests suggest that the genotoxicity of AMK is directly related to the AAs contents in AMK.

  9. Genotoxicity and antigenotoxicity assessment of shiitake (Lentinula edodes (Berkeley Pegler using the Comet assay

    Directory of Open Access Journals (Sweden)

    CK Miyaji

    2004-01-01

    Full Text Available The mushroom shiitake (Lentinula edodes (Berkeley Pegler is been widely consumed in many countries, including Brazil, because of its pleasant flavor and reports of its therapeutic properties, although there is little available information on the genotoxicity and/or antigenotoxicity of this mushroom. We used the Comet assay and HEp-2 cells to evaluate the in vitro genotoxic and antigenotoxic activity of aqueous extracts of shiitake prepared in three different concentrations (0.5, 1.0 and 1.5 mg/mL and three different temperatures (4, 22 and 60 °C, using methyl methanesulfonate (MMS as a positive control and untreated cells as a negative control. Two concentrations (1.0 and 1.5 mg/mL of extract prepared at 4 °C and all of the concentrations prepared at 22 ± 2 and 60 °C showed moderate genotoxic activity. To test the protective effect of the three concentrations of the extracts against the genotoxicity induced by methyl methanesulfonate, three protocols were used: pre-treatment, simultaneous-treatment and post-treatment. Treatments were repeated for all combinations of preparation temperature and concentration. Two extracts (22 ± 2 °C 1.0 mg/mL (simultaneous-treatment and 4 °C 0.5 mg/mL (post-treatment showed antigenotoxic activity.

  10. 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.

  11. 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.

  12. Specific plant DNA adducts as molecular biomarkers of genotoxic atmospheric environments.

    Science.gov (United States)

    Weber-Lotfi, F; Obrecht-Pflumio, S; Guillemaut, P; Kleinpeter, J; Dietrich, A

    2005-03-01

    The general purpose of this study was to determine whether the formation of DNA addition products ('adducts') in plants could be a valuable biomarker of genotoxic air pollution. Plants from several species were exposed to ambient atmosphere at urban and suburban sites representative of different environmental conditions. The levels of NO2 and of the quantitatively major genotoxic air pollutants benzene, toluene, and xylene were monitored in parallel with plant exposure. DNA adducts were measured in bean (Phaseolus vulgaris), rye-grass (Lolium perenne), and tobacco (Nicotiana tabacum) seedlings by means of the [32P]-postlabeling method. Whereas, no correlation was found between the levels of the major genotoxic air pollutants and the total amounts of DNA adducts, individual analyses revealed site-specific and plant species-specific adduct responses, both at the qualitative and quantitative level. Among these, the amount of a specific rye-grass DNA adduct (rgs1) correlated with benzene/toluene/xylene levels above a threshold. For further characterization, rye-grass seedlings were treated in controlled conditions with benzene, toluene, xylene or their derivatives. On the other hand, in vitro DNA adduct formation assays were developed involving benzene, toluene, xylene, or their derivatives, and plant microsomes or purified peroxidase. Although in some cases, these approaches produced specific adduct responses, they failed to generate the rgs1 DNA adduct, which appeared to be characteristic for on-site test-plant exposure. Our studies have thus identified an interesting candidate for further analysis of environmental biomarkers of genotoxicity.

  13. Comparative Metabolism, Cytotoxicity, and Genotoxicity of Chemical Carcinogens in Primary Cultures of Hepatocytes

    Science.gov (United States)

    1985-05-01

    metabolism was assessed 30-36 hours after the addition of TCDD. 244 A suspected hepatocarcinogen, senecionine, a pyrrolizidine alkaloid isolated from...and J. L. Byard (1981), Metabolism, cytotoxicity and genotoxicity of the pyrrolizidine alkaloid sene- cionine in primary cultures of rat hepatocytes

  14. Levels of Genotoxic and Carcinogenic Compounds in Plant food Supplements and Associated Risk Assessment

    NARCIS (Netherlands)

    Berg, van den S.J.P.L.; Restani, P.; Boersma, M.G.; Delmulle, L.; Rietjens, I.

    2011-01-01

    The present study describes the selection, analysis and risk assessment of genotoxic and carcinogenic compounds of botanicals and botanical preparations which can be found in plant food supplements (PFS). First an inventory was made of botanical compounds that are of possible concern for human healt

  15. Genotoxicity evaluation of wood-derived and vegetable oil-derived stanol esters

    NARCIS (Netherlands)

    Turnbull, D.; Frankos, V.H.; Delft, J.H.M. van; Vogel, N. de

    1999-01-01

    Plant stanol esters from wood and vegetable oil sources were tested for genotoxicity in bacterial (Salmonella typhimurium) and mammalian cell (L5178Y) gene mutation assays and in a mammalian cell chromosome aberration assay (CHO cells). The two stanol ester formulations were tested separately at dos

  16. Genotoxicity--threshold or not? Introduction of cases of industrial chemicals.

    Science.gov (United States)

    Bolt, Hermann M

    2003-04-11

    Many industrially and environmentally important industrial carcinogens display effects that lead them to be viewed and regulated as 'genotoxic compounds'. Some of these chemicals cause experimental tumours only at high or toxic doses. The current view is that non-threshold principles should be applied for risk assessments and to define permissible exposure values. The toxicological impact of underlying mechanisms is frequently not well investigated and understood. The classification of carcinogens is now in a state of discussion. In Germany, the 'MAK-Commission' has issued new recommendations to distinguish between 5 groups of proven and suspected carcinogens. This proposal includes a category of 'substances with carcinogenic potential for which genotoxicity plays no or at most a minor role'. Another category comprises 'substances with carcinogenic and genotoxic potential, the potency of which is considered so low that, provided that the MAK-value is observed, no significant contribution to human cancer risk is to be expected'. There is also a number of apparently genotoxic carcinogens where the existence of 'practical thresholds' is at least debated. One outstanding example is vinyl acetate, which must be viewed against the background of discussions on other industrial high-volume chemicals like formaldehyde, acrylonitrile, acrylamide and trichloroethylene. Main arguments in favour or against thresholds of carcinogenicity of these individual compounds are summarised. Current instruments of regulation should be adjusted to allow adequate consideration of carcinogenic effects of chemicals that are practically relevant at high doses only. Also, research into this field is encouraged.

  17. Genotoxicity evaluation of dental restoration nanocomposite using comet assay and chromosome aberration test

    Science.gov (United States)

    Musa, Marahaini; Thirumulu Ponnuraj, Kannan; Mohamad, Dasmawati; Rahman, Ismail Ab

    2013-01-01

    Nanocomposite is used as a dental filling to restore the affected tooth, especially in dental caries. The dental nanocomposite (KelFil) for tooth restoration used in this study was produced by the School of Dental Sciences, Universiti Sains Malaysia, Malaysia and is incorporated with monodispersed, spherical nanosilica fillers. The aim of the study was to determine the genotoxic effect of KelFil using in vitro genotoxicity tests. The cytotoxicity and genotoxicity of KelFil was evaluated using MTT assay, comet assay and chromosome aberration tests with or without the addition of a metabolic activation system (S9 mix), using the human lung fibroblast cell line (MRC-5). Concurrent negative and positive controls were included. In the comet assay, no comet formation was found in the KelFil groups. There was a significant difference in tail moment between KelFil groups and positive control (p < 0.05). Similarly, no significant aberrations in chromosomes were noticed in KelFil groups. The mitotic indices of treatment groups and negative control were significantly different from positive controls. Hence, it can be concluded that the locally produced dental restoration nanocomposite (KelFil) is non-genotoxic under the present test conditions.

  18. What is Comet assay not telling us: AFLP reveals wider aspects of genotoxicity.

    Science.gov (United States)

    Šrut, Maja; Štambuk, Anamaria; Klobučar, Göran I V

    2013-06-01

    DNA damage detected by genotoxicity biomarkers such as the Comet assay is not always a reliable indicator of the consequences that genotoxic agents can have on the genome integrity of the exposed organisms. Therefore, to reveal the existence of more permanent alterations of DNA structure after genotoxic stress, the RTG-2 rainbow trout cell line was exposed for 3 days to benzo[a]pyrene (B[a]P, 0.1-10 μM) and ethyl methanesulfonate (EMS, 0.1-1mM) followed by 3 days of recovery period. Primary DNA damage was evaluated by the Comet assay and DNA alterations were assessed using AFLP (amplified fragment length polymorphism). Qualitative and quantitative modifications in AFLP profiles were analyzed in order to detect genetic alterations arising from mutation events and/or DNA damage. Significant induction in DNA damage measured by the Comet assay was noticed after B[a]P treatment at all concentrations but values returned to the control level after recovery. Exposure to EMS induced significant DNA damage only at the highest concentration and damage persisted after the recovery period. AFLP profiles detected DNA alterations even when Comet assay indicated complete DNA repair, revealing more persistent damage. Since such DNA damage can impair its structure and function, Comet assay results should preferably be supplemented with other methods in order to predict the consequences of genotoxic insult more accurately.

  19. 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.

  20. Evaluation of the Bronchorelaxant, Genotoxic, and Antigenotoxic Effects of Cassia alata L.

    Directory of Open Access Journals (Sweden)

    M. Ouédraogo

    2013-01-01

    Full Text Available Aqueous-ethanolic extract of Cassia alata (AECal and its derived fractions obtained through liquid-liquid fractionation were evaluated for their bronchorelaxant, genotoxic, and antigenotoxic effects. Contractile activity of rats’ tracheas in the presence of tested materials, as well as its modifications with different inhibitors and blockers, was isometrically recorded. The antigenotoxic potential of AECal was evaluated on cyclophosphamide- (CP- induced genotoxicity in the rat. Animals were pretreated with the extract, then liver comet assay was performed. AECal and its chloroformic fractions (CF-AECal relaxed the contraction induced by Ach, but both were significantly less potent in inhibiting contraction induced by KCl (30 mM; 80 mM. Propranolol, indomethacin, L-NAME, methylene blue, and glibenclamide did not modify the relaxant effect of CF-AECal. TEA altered the response of trachea to CF-AECal. CF-AECal caused a rightward shift without affecting the Emax in cumulative concentration-response curves of Ach only at low concentrations. In animals pretreated with the extract, the percentage of CP-induced DNA damage decreased. Our results suggest that (1 muscarinic receptors contribute at least in part to the relaxant effects of CF-AECal; (2 CF-AECal interferes with membrane polarization; and (3 AECal is not genotoxic in vivo and contains chemopreventive phytoconstituents offering protection against CP-induced genotoxicity.

  1. Genotoxic potency of mercuric chloride in gill cells of marine gastropod Planaxis sulcatus using comet assay

    Digital Repository Service at National Institute of Oceanography (India)

    Bhagat, J.; Ingole, B.S.

    In vivo and in vitro exposures were used to investigate the genotoxicity of mercuric chloride (HgCl2) to the marine snail, Planaxis sulcatus. The comet assay protocol was validated on gill cells exposed in vitro to hydrogen peroxide (H...

  2. The Cytotoxicity and Genotoxicity of Particulate and Soluble Cobalt in Human Urothelial Cells.

    Science.gov (United States)

    Speer, Rachel M; The, Therry; Xie, Hong; Liou, Louis; Adam, Rosalyn M; Wise, John Pierce

    2017-03-21

    Cobalt use is increasing particularly due to its use as one of the primary metals in cobalt-chromium-molybdenum (CoCrMo) metal-on-metal prosthetics. CoCrMo is a high-strength, wear-resistant alloy with reduced risk for prosthetic loosening and device fracture. More than 500,000 people receive hip implants each year in the USA which puts them at potential risk for exposure to metal ions and particles released by the prosthetic implants. Data show cobalt ions released from prosthetics reach the bloodstream and accumulate in the bladder. As patients with failed hip implants show increased urinary and blood cobalt levels, no studies have considered the effects of cobalt on human urothelial cells. Accordingly, we investigated the cytotoxic and genotoxic effects of particulate and soluble cobalt in urothelial cells. Exposure to both particulate and soluble cobalt resulted in a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ions. Based on intracellular cobalt ion levels, we found, when compared to particulate cobalt, soluble cobalt was more cytotoxic, but induced similar levels of genotoxicity. Interestingly, at similar intracellular cobalt ion concentrations, soluble cobalt induced cell cycle arrest indicated by a lack of metaphases not observed after particulate cobalt treatment. These data indicate that cobalt compounds are cytotoxic and genotoxic to human urothelial cells and solubility may play a key role in cobalt-induced toxicity.

  3. Chlorination of oxybenzone: Kinetics, transformation, disinfection byproducts formation, and genotoxicity changes.

    Science.gov (United States)

    Zhang, Shujuan; Wang, Xiaomao; Yang, Hongwei; Xie, Yuefeng F

    2016-07-01

    UV filters are a kind of emerging contaminant, and their transformation behavior in water treatment processes has aroused great concern. In particular, toxic products might be produced during reaction with disinfectants during the disinfection process. As one of the most widely used UV filters, oxybenzone has received significant attention, because its transformation and toxicity changes during chlorine oxidation are a concern. In our study, the reaction between oxybenzone and chlorine followed pseudo-first-order and second-order kinetics. Three transformation products were detected by LC-MS/MS, and the stability of products followed the order of tri-chloro-methoxyphenoyl > di-chlorinated oxybenzone > mono-chlorinated oxybenzone. Disinfection byproducts (DBPs) including chloroform, trichloroacetic acid, dichloroacetic acid and chloral hydrate were quickly formed, and increased at a slower rate until their concentrations remained constant. The maximum DBP/oxybenzone molar yields for the four compounds were 12.02%, 6.28%, 0.90% and 0.23%, respectively. SOS/umu genotoxicity test indicated that genotoxicity was highly elevated after chlorination, and genotoxicity showed a significantly positive correlation with the response of tri-chloro-methoxyphenoyl. Our results indicated that more genotoxic transformation products were produced in spite of the elimination of oxybenzone, posing potential threats to drinking water safety. This study shed light on the formation of DBPs and toxicity changes during the chlorination process of oxybenzone.

  4. Way forward in case of a false positive in vitro genotoxicity result for a cosmetic substance?

    Science.gov (United States)

    Doktorova, Tatyana Y; Ates, Gamze; Vinken, Mathieu; Vanhaecke, Tamara; Rogiers, Vera

    2014-02-01

    The currently used regulatory in vitro mutagenicity/genotoxicity test battery has a high sensitivity for detecting genotoxicants, but it suffers from a large number of irrelevant positive results (i.e. low specificity) thereby imposing the need for additional follow-up by in vitro and/or in vivo genotoxicity tests. This could have a major impact on the cosmetic industry in Europe, seen the imposed animal testing and marketing bans on cosmetics and their ingredients. Afflicted, but safe substances could therefore be lost. Using the example of triclosan, a cosmetic preservative, we describe here the potential applicability of a human toxicogenomics-based in vitro assay as a potential mechanistically based follow-up test for positive in vitro genotoxicity results. Triclosan shows a positive in vitro chromosomal aberration test, but is negative during in vivo follow-up tests. Toxicogenomics analysis unequivocally shows that triclosan is identified as a compound acting through non-DNA reactive mechanisms. This proof-of-principle study illustrates the potential of genome-wide transcriptomics data in combination with in vitro experimentation as a possible weight-of-evidence follow-up approach for de-risking a positive outcome in a standard mutagenicity/genotoxicity battery. As such a substantial number of cosmetic compounds wrongly identified as genotoxicants could be saved for the future.

  5. Genotoxicity of styrene oligomers extracted from polystyrene intended for use in contact with food

    Directory of Open Access Journals (Sweden)

    Makoto Nakai

    2014-01-01

    Full Text Available Here, we conducted in vitro genotoxicity tests to evaluate the genotoxicity of styrene oligomers extracted from polystyrene intended for use in contact with food. Styrene oligomers were extracted with acetone and the extract was subjected to the Ames test (OECD test guideline No. 471 and the in vitro chromosomal aberration test (OECD test guideline No. 473 under good laboratory practice conditions. The concentrations of styrene dimers and trimers in the concentrated extract were 540 and 13,431 ppm, respectively. Extraction with acetone provided markedly higher concentrations of styrene oligomers compared with extraction with 50% ethanol aqueous solution, which is the food simulant currently recommended for use in safety assessments of polystyrene by both the United States Food and Drug Administration and the European Food Safety Authority. And these high concentrations of styrene dimers and trimers were utilized for the evaluation of genotoxicity in vitro. Ames tests using five bacterial tester strains were negative both in the presence or absence of metabolic activation. The in vitro chromosomal aberration test using Chinese hamster lung cells (CHL/IU was also negative. Together, these results suggest that the risk of the genotoxicity of styrene oligomers that migrate from polystyrene food packaging into food is very low.

  6. Evaluation of the Genotoxicity and Cytotoxicity of Semipurified Fractions from the Mediterranean Brown Algae, Dictyopteris membranacea

    Science.gov (United States)

    Akremi, Najoua; Cappoen, Davie; Anthonissen, Roel; Bouraoui, Abderrahman; Verschaeve, Luc

    2016-01-01

    Dictyopteris membranacea, a species of Mediterranean brown algae, is believed to have potential pharmacological and nutritional applications. However, such potentials only make sense when devoid of any adverse health consequences. The present study should be seen in this context. It aimed at evaluating the genotoxicity and cytoxicity of its organic extract (F0) and semi purified fractions (F4, F5, and F6). Extracts were tested using the bacterial Vitotox® test and micronucleus assay in different concentrations (from 1.25 μg/mL up to 100 μg/mL, depending on the test and the extract). Applied concentrations were based on a preliminary dose-finding test with the neutral red uptake assay. The results show that all extracts were not genotoxic in the presence or absence of a rat metabolic enzyme fraction (S9). This is encouraging and justifies further investigations on the therapeutic and other values of this algae. SUMMARY Dictyopteris membranacea extracts and some of their semi purified fractions have important antibacterial properties.The organic extract (F0) and semi purified fractions (F4, F5, and F6) were not genotoxic according to the bacterial Vitotox test.They were also not genotoxic according to the micronucleus test in human C3A cells.Applied concentrations were based on the in-vitro neutral red uptake (NRU) test. PMID:27761065

  7. Study on the genotoxicity of HA/ZrO{sub 2} composite particles in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Quan, Renfu, E-mail: quanrenfu8@yahoo.com [Xiaoshan Traditional Chinese Medical Hospital, ZhengJiang Province 311200 (China); Tang, Yanghua; Huang, Zhongming; Xu, Jinwei [Xiaoshan Traditional Chinese Medical Hospital, ZhengJiang Province 311200 (China); Wu, Xiaochen [School of Materials Science and Engineering, Shanghai University, Shanghai (China); Yang, Disheng [Department of Orthopedics, the second Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310009 (China)

    2013-04-01

    To evaluate the genotoxicity of the HA/ZrO{sub 2} composite particles by using the micronucleus test (MNT) in vitro. HA/ZrO{sub 2} composite particles prepared by sintering at high temperature and pressure, that used powder of HA and ZrO{sub 2} of different proportions, were compared with pure HA particles and pure ZrO{sub 2} particles. The effect of the composite particles on cell proliferation of rabbit mesenchymal stem cells, and its the genotoxicity to rabbit mesenchymal stem cells were detected by MNT method. The MTT test showed that both pure HA particles and composite particles which contained HA promoted cell proliferation of rabbit mesenchymal stem cells, while pure ZrO{sub 2} particles did not, and there was a significant difference (P < 0.05). The MNT test showed no significant difference between the HA group and the negative control group (P > 0.05), but a significant difference between the HA group and the positive control group (P < 0.05). The difference between the ZrO{sub 2} group and the negative control group was significant (P < 0.01), while the difference between the ZrO{sub 2} group and the positive control group was insignificant (P > 0.05). The genotoxicity of the HA/ZrO{sub 2} composite particle increased with a higher proportion of ZrO{sub 2} and an increase in the concentration of the composite, and the 30 wt.% HA/70% ZrO{sub 2} composite with 200 μg/mL concentration showed significant genotoxicity (P < 0.01). - Highlights: ► HA/ZrO{sub 2} composite particles were prepared by sintering used powder of HA and ZrO{sub 2} of different proportions. ► Evaluate the genotoxicity of the HA/ZrO{sub 2} composite particle in vitro micronucleus test (MNT). ► The genotoxicity of the HA/ZrO{sub 2} composite particle increased with an increase in the proportion of ZrO{sub 2}. ► The 30%wtHA/70% ZrO{sub 2} composite with 200 μg/mL concentration showed significant genotoxicity.

  8. 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

  9. Ecotoxicity and genotoxicity assessment of cytotoxic antineoplastic drugs and their metabolites.

    Science.gov (United States)

    Zounkova, Radka; Kovalova, Lubomira; Blaha, Ludek; Dott, Wolfgang

    2010-09-01

    In spite of growing scientific concern about pharmaceuticals in the environment, there is still a lack of information especially with regard to their metabolites. The present study investigated ecotoxicity and genotoxicity of three widely used cytostatic agents 5-fluorouracil (5-FU), cytarabine (CYT) and gemcitabine (GemC) and their major human metabolites, i.e. alpha-fluoro-beta-alanine (FBAL), uracil-1-beta-D-arabinofuranoside (AraU) and 2',2'-difluorodeoxyuridine (dFdU), respectively. Effects were studied in acute immobilization and reproduction assays with crustacean Daphnia magna and growth inhibition tests with alga Desmodesmus subspicatus and bacteria Pseudomonas putida. Genotoxicity was tested with umu-test employing Salmonella choleraesius subsp. chol. Toxicity was relatively high at parent compounds with EC(50) values ranging from 44 microg L(-1) (5-fluorouracil in the P. putida test) to 200 mg L(-1) (cytarabine in D. magna acute test). In general, the most toxic compound was 5-FU. Studied metabolites showed low or no toxicity; only FBAL (metabolite of 5-FU) showed low toxicity to D. subspicatus and P. putida with EC(50) values 80 and 140 mg L(-1), respectively. All parent cytostatics showed genotoxicity with minimum genotoxic concentrations (MGC) ranging from 40 to 330 mg L(-1). From metabolites, only FBAL was genotoxic in high concentrations. To our knowledge, the present study provides some of the first ecotoxicity data for both cytostatics and their metabolites, which might further serve for serious evaluation of ecological risks. The observed EC(50) values within the microg L(-1) range were fairly close to concentrations reported in hospital sewage water, which indicates further research needs, especially studies of chronic toxicity.

  10. Screening of genotoxicity and mutagenicity in extractable organics from oil sands process-affected water.

    Science.gov (United States)

    Zetouni, Nikolas C; Siraki, Arno G; Weinfeld, Michael; Pereira, Alberto Dos Santos; Martin, Jonathan W

    2016-11-01

    Large volumes of oil sands process-affected water (OSPW) are produced by the oil sands surface mining industry during alkaline hot-water extraction of bitumen. It is well documented that the acid extractable organics (AEOs) in OSPW, a highly complex mixture of acidic and polar neutral substances, are acutely toxic; but few studies have examined the genotoxicity or mutagenicity of this mixture. In the present study, the in vitro SOS Chromotest and the Ames test (TA98 and TA100 strains) were used to evaluate genotoxicity and mutagenicity for whole OSPW AEOs in the presence and absence of biotransformation by rat S9 liver enzymes. Two subfractions were also examined in the same assays: neutral extractable fraction (F1-NE), and the subsequent acid extractable fraction (F2-AE). In the SOS assay, whole AEO was cytotoxic when concentrated 2× (i.e., twice as concentrated as the environmental sample) and showed increasing genotoxic response above 6×. Co-exposure with S9 had a protective effect on the cell SOS-inducing factor and survival but did not eliminate genotoxicity above 6× concentrations. Most of the cytotoxicity was attributable to F2-AE, but both F1-NE and F2-AE had similar genotoxic dose-responses above 6×. In the Ames test without S9, whole AEO was mutagenic in both strains above 10× concentrations. Co-incubation with S9 had little effect on the TA100 strain but with TA98 resulted in bioactivation at midlevel doses (1.5-6.3×) and protection at higher doses (10-25×). The 2 subfractions were mutagenic in both strains but with different dose-responses. Further research in vivo or in more relevant cells is warranted to investigate the carcinogenic risks of OSPW. Environ Toxicol Chem 2016;9999:1-8. © 2016 SETAC.

  11. Genotoxicity assessment of magnetic iron oxide nanoparticles with different particle sizes and surface coatings

    Science.gov (United States)

    Liu, Yanping; Xia, Qiyue; Liu, Ying; Zhang, Shuyang; Cheng, Feng; Zhong, Zhihui; Wang, Li; Li, Hongxia; Xiao, Kai

    2014-10-01

    Magnetic iron oxide nanoparticles (IONPs) have been widely used for various biomedical applications such as magnetic resonance imaging and drug delivery. However, their potential toxic effects, including genotoxicity, need to be thoroughly understood. In the present study, the genotoxicity of IONPs with different particle sizes (10, 30 nm) and surface coatings (PEG, PEI) were assessed using three standard genotoxicity assays, the Salmonella typhimurium reverse mutation assay (Ames test), the in vitro mammalian chromosome aberration test, and the in vivo micronucleus assay. In the Ames test, SMG-10 (PEG coating, 10 nm) showed a positive mutagenic response in all the five test bacterial strains with and without metabolic activation, whereas SEI-10 (PEI coating, 10 nm) showed no mutagenesis in all tester strains regardless of metabolic activation. SMG-30 (PEG coating, 30 nm) was not mutagenic in the absence of metabolic activation, and became mutagenic in the presence of metabolic activation. In the chromosomal aberration test, no increase in the incidence of chromosomal aberrations was observed for all three IONPs. In the in vivo micronucleus test, there was no evidence of increased micronuclei frequencies for all three IONPs, indicating that they were not clastogenic in vivo. Taken together, our results demonstrated that IONPs with PEG coating exhibited mutagenic activity without chromosomal and clastogenic abnormalities, and smaller IONPs (SMG-10) had stronger mutagenic potential than larger ones (SMG-30); whereas, IONPs with SEI coating (SEI-10) were not genotoxic in all three standard genotoxicity assays. This suggests that the mutagenicity of IONPs depends on their particle size and surface coating.

  12. Genotoxic effects in wild rodents (Rattus rattus and Mus musculus) in an open coal mining area.

    Science.gov (United States)

    León, Grethel; Pérez, Lyda Espitia; Linares, Juan Carlos; Hartmann, Andreas; Quintana, Milton

    2007-06-15

    Coal is a mixture of a variety of compounds containing mutagenic and carcinogenic polycyclic aromatic hydrocarbons. Exposure to coal is considered as an important non-cellular and cellular source of reactive oxygen species that can induce DNA damage. In addition, spontaneous combustion can occur in coal mining areas, further releasing compounds with detrimental effects on the environment. In this study the comet assay was used to investigate potential genotoxic effects of coal mining activities in peripheral blood cells of the wild rodents Rattus rattus and Mus musculus. The study was conducted in a coal mining area of the Municipio de Puerto Libertador, South West of the Departamento de Cordoba, Colombia. Animals from two areas in the coal mining zone and a control area located in the Municipio de Lorica were investigated. The results showed evidence that exposure to coal results in elevated primary DNA lesions in blood cells of rodents. Three different parameters for DNA damage were assessed, namely, DNA damage index, migration length and percentage damaged cells. All parameters showed statistically significantly higher values in mice and rats from the coal mining area in comparison to the animals from the control area. The parameter "DNA Damage Index" was found to be most sensitive and to best indicate a genotoxic hazard. Both species investigated were shown to be sensitive indicators of environmental genotoxicity caused by coal mining activities. In summary, our study constitutes the first investigation of potential genotoxic effects of open coal mining carried out in Puerto Libertador. The investigations provide a guide for measures to evaluate genotoxic hazards, thereby contributing to the development of appropriate measures and regulations for more careful operations during coal mining.

  13. Genotoxicity of silver nanoparticles evaluated using the Ames test and in vitro micronucleus assay.

    Science.gov (United States)

    Li, Yan; Chen, David H; Yan, Jian; Chen, Ying; Mittelstaedt, Roberta A; Zhang, Yongbin; Biris, Alexandru S; Heflich, Robert H; Chen, Tao

    2012-06-14

    Silver nanoparticles (AgNPs) have antimicrobial properties, which have contributed to their widespread use in consumer products. A current issue regarding nanomaterials is the extent to which existing genotoxicity assays are useful for evaluating the risks associated with their use. In this study, the genotoxicity of 5 nm AgNPs was assessed using two standard genotoxicity assays, the Salmonella reverse mutation assay (Ames test) and the in vitro micronucleus assay. Using the preincubation version of the Ames assay, Salmonella strains TA102, TA100, TA1537, TA98, and TA1535 were treated with 0.15-76.8 μg/plate of the AgNPs. Toxicity limited the doses that could be assayed to 2.4-38.4 μg/plate; no increases in mutant frequency over the vehicle control were found for the concentrations that could be assayed. Human lymphoblastoid TK6 cells were treated with 10-30 μg/ml AgNPs, and additional cells were treated with water and 0.73 gy X-rays as vehicle and positive controls. Micronucleus frequency was increased by the AgNP treatment in a dose-dependent manner. At a concentration of 30 μg/ml (with 45.4% relative population doubling), AgNPs induced a significant, 3.17-fold increase with a net increase of 1.60% in micronucleus frequency over the vehicle control, a weak positive response by our criteria. These results demonstrate that the 5 nm AgNP are genotoxic in TK6 cells. Also, the data suggest that the in vitro micronucleus assay may be more appropriate than the Ames test for evaluating the genotoxicity of the AgNPs.

  14. Characterisation of acute toxicity, genotoxicity and oxidative stress posed by textile effluent on zebrafish

    Institute of Scientific and Technical Information of China (English)

    Wenjuan Zhang; Wei Liu; Jing Zhang; Huimin Zhao; Yaobin Zhang; Xie Quan; Yihe Jin

    2012-01-01

    Textile industries are important sources of toxic discharges and contribute enormously to water deterioration,while little attention has been paid to the toxicity of textile effluents in discharge regulation.Bioassays with zebrafish were employed to evaluate the toxicity of wastewater samples collected from different stages at a textile factory and sewage treatment plants (STPs).Physico-chemical parameters,acute toxicity,genotoxicity and oxidative stress biomarkers were analyzed.The wastewater samples from bleaching,rinsing and soaping of the textile factory exhibited high acute toxicity and genotoxicity.The coexisting components of dye compounds,as assistants and oxidants,seemed to cause some effect on the toxic response.After treatment employing the anoxic-oxic (A/O) process in STPs,the color and the chemical oxygen demand (COD) were reduced by 40% and 84%,respectively,falling within the criteria of the Chinese Sewage Discharge Standard.In contrast,increases in acute toxicity and genotoxicity were observed in the anaerobic tank,indicating the formation of toxic intermediates.The genotoxicity of the effluent of the STP was not significantly different from that of the influent,suggesting the wastewater treatment processes were not effective in removing the genotoxicity of the dye wastewater.Results indicated that the effluent contains pro-oxidants since the activities of glutathione (GSH),malondialdehyde (MDA),and total anti-oxidation capacity (T-AOC) were all elevated.In addition,decreases in superoxide dismutase (SOD) and glutathione-S transferase (GST) activities observed can be interpreted as a cytotoxicity sign due to an over-production of reactive oxygen species (ROS).The results of the present study suggest that the STPs were not capable of reducing the toxicity of wastewater sufficiently.Further treatment is needed to remove the potential risks posed by textile effluent to ecosystems and human health,and employing a toxicity index is necessary for

  15. 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.

  16. Ground and surface water for drinking: a laboratory study on genotoxicity using plant tests

    Directory of Open Access Journals (Sweden)

    Donatella Feretti

    2012-02-01

    Full Text Available Surface waters are increasingly utilized for drinking water because groundwater sources are often polluted. Several monitoring studies have detected the presence of mutagenicity in drinking water, especially from surface sources due to the reaction of natural organic matter with disinfectant. The study aimed to investigate the genotoxic potential of the products of reaction between humic substances, which are naturally present in surface water, and three disinfectants: chlorine dioxide, sodium hypochlorite and peracetic acid. Commercial humic acids dissolved in distilled water at different total organic carbon (TOC concentrations were studied in order to simulate natural conditions of both ground water (TOC=2.5 mg/L and surface water (TOC=7.5 mg/L. These solutions were treated with the biocides at a 1:1 molar ratio of C:disinfectant and tested for genotoxicity using the anaphase chromosomal aberration and micronucleus tests in Allium cepa, and the Vicia faba and Tradescantia micronucleus tests. The tests were carried out after different times and with different modes of exposure, and at 1:1 and 1:10 dilutions of disinfected and undisinfected humic acid solutions. A genotoxic effect was found for sodium hypochlorite in all plant tests, at both TOCs considered, while chlorine dioxide gave positive results only with the A.cepa tests. Some positive effects were also detected for PAA (A.cepa and Tradescantia. No relevant differences were found in samples with different TOC values. The significant increase in all genotoxicity end-points induced by all tested disinfectants indicates that a genotoxic potential is exerted even in the presence of organic substances at similar concentrations to those frequently present in drinking water.

  17. In vivo genotoxicity assessment of titanium, zirconium and aluminium nanoparticles, and their microparticulated forms, in Drosophila.

    Science.gov (United States)

    Demir, Eşref; Turna, Fatma; Vales, Gerard; Kaya, Bülent; Creus, Amadeu; Marcos, Ricard

    2013-11-01

    As in vivo system, we propose Drosophila melanogaster as a useful model for study the genotoxic risks associated with nanoparticle exposure. In this study we have carried out a genotoxic evaluation of titanium dioxide (TiO2), zirconium oxide (ZrO2) and aluminium oxide (Al2O3) nanoparticles and their microparticulated forms in D. melanogaster by using the wing somatic mutation and recombination assay. This assay is based on the principle that loss of heterozygosis and the corresponding expression of the suitable recessive markers, multiple wing hairs and flare-3, can lead to the formation of mutant clones in treated larvae, which are expressed as mutant spots on the wings of adult flies. Third instar larvae were feed with TiO2, ZrO2 and Al2O3 nanoparticles, and their microparticulated forms, at concentrations ranging from 0.1 to 10mM. Although a certain level of aggregation/agglomeration was observed in solution, it must be noted than the constant digging activity of larvae ensures that treated medium pass constantly through the digestive tract ensuring exposure. The results showed that no significant increases in the frequency of all spots (e.g. small single, large single, twin, total mwh and total spots) were observed, indicating that these nanoparticles were not able to induce genotoxic activity in the wing spot assay of D. melanogaster. Negative data were also obtained with the microparticulated forms. This indicates that the nanoparticulated form of the selected nanomaterials does not modify the potential genotoxicity of their microparticulated versions. These in vivo results contribute to increase the genotoxicity database on the TiO2, ZrO2 and Al2O3 nanoparticles.

  18. Genotoxicity assessment of magnetic iron oxide nanoparticles with different particle sizes and surface coatings.

    Science.gov (United States)

    Liu, Yanping; Xia, Qiyue; Liu, Ying; Zhang, Shuyang; Cheng, Feng; Zhong, Zhihui; Wang, Li; Li, Hongxia; Xiao, Kai

    2014-10-24

    Magnetic iron oxide nanoparticles (IONPs) have been widely used for various biomedical applications such as magnetic resonance imaging and drug delivery. However, their potential toxic effects, including genotoxicity, need to be thoroughly understood. In the present study, the genotoxicity of IONPs with different particle sizes (10, 30 nm) and surface coatings (PEG, PEI) were assessed using three standard genotoxicity assays, the Salmonella typhimurium reverse mutation assay (Ames test), the in vitro mammalian chromosome aberration test, and the in vivo micronucleus assay. In the Ames test, SMG-10 (PEG coating, 10 nm) showed a positive mutagenic response in all the five test bacterial strains with and without metabolic activation, whereas SEI-10 (PEI coating, 10 nm) showed no mutagenesis in all tester strains regardless of metabolic activation. SMG-30 (PEG coating, 30 nm) was not mutagenic in the absence of metabolic activation, and became mutagenic in the presence of metabolic activation. In the chromosomal aberration test, no increase in the incidence of chromosomal aberrations was observed for all three IONPs. In the in vivo micronucleus test, there was no evidence of increased micronuclei frequencies for all three IONPs, indicating that they were not clastogenic in vivo. Taken together, our results demonstrated that IONPs with PEG coating exhibited mutagenic activity without chromosomal and clastogenic abnormalities, and smaller IONPs (SMG-10) had stronger mutagenic potential than larger ones (SMG-30); whereas, IONPs with SEI coating (SEI-10) were not genotoxic in all three standard genotoxicity assays. This suggests that the mutagenicity of IONPs depends on their particle size and surface coating.

  19. Matching colonic polyps using correlation optimized warping

    Science.gov (United States)

    Wang, Shijun; Yao, Jianhua; Petrick, Nicholas; Summers, Ronald M.

    2010-03-01

    Computed tomographic colonography (CTC) combined with a computer aided detection system has the potential for improving colonic polyp detection and increasing the use of CTC for colon cancer screening. In the clinical use of CTC, a true colonic polyp will be confirmed with high confidence if a radiologist can find it on both the supine and prone scans. To assist radiologists in CTC reading, we propose a new method for matching polyp findings on the supine and prone scans. The method performs a colon registration using four automatically identified anatomical salient points and correlation optimized warping (COW) of colon centerline features. We first exclude false positive detections using prediction information from a support vector machine (SVM) classifier committee to reduce initial false positive pairs. Then each remaining CAD detection is mapped to the other scan using COW technique applied to the distance along the centerline in each colon. In the last step, a new SVM classifier is applied to the candidate pair dataset to find true polyp pairs between supine and prone scans. Experimental results show that our method can improve the sensitivity to 0.87 at 4 false positive pairs per patient compared with 0.72 for a competing method that uses the normalized distance along the colon centerline (p<0.01).

  20. CT in the diagnosis of colonic diverticulitis

    Energy Technology Data Exchange (ETDEWEB)

    Narumi, Yoshifumi; Mitani, Takashi; Kuriyama, Keiko

    1987-11-01

    Pericolic abscess is the most frequent complication of colonic diverticulitis which requires an accurate diagnosis on its location, extent, and complications. Double-contrast barium enema (DCBE) was able to reveal indirect signs such as displacement of the colon and contrast material in the abscess cavity. Conventional Computed tomography (CT) of the colon could not demonstrate a pericolic abscess and thickened colonic wall clearly. We tried to demonstrate direct signs of pericolic abscess and thickened colonic wall by administering 200 ml of olive oil per anum. Additionally, to demonstrate the fistulous tract between sigmoid colon and urinary bladder, 200 ml of 0.8% barium solution was administered first per anum, and then evacuated prior to administering olive oil. The DCBE and CT examination in 4 patients with a clinical diagnosis (2 cases) or surgically confirmed diagnosis (2 cases) of colonic diverticulitis were studied to determine the sensitivity of the two technics. Our results showed that CT was significantly superior to the DCBE in visualising the location and extent of pericolic inflammatory process, especially colovesical fistula, the most severe complication of pericolic abscess.

  1. Colon targeted curcumin delivery using guar gum.

    Science.gov (United States)

    Elias, Edwin J; Anil, Singhal; Ahmad, Showkat; Daud, Anwar

    2010-06-01

    Curcumin is used in the treatment of colon cancer, but its very poor absorption in the upper part of the GIT is a major concern. As a site for drug delivery, the colon offers a near neutral pH, reduced digestive enzymatic activity, a long transit time and an increased responsiveness to absorption enhancers. The aim of the present study was to identify a suitable polymer (guar gum) based matrix tablet for curcumin with sufficient mechanical strength and promising in vitro mouth-to-colon release profile. Three formulations of curcumin were prepared using varying concentrations of guar gum containing 50 mg curcumin by the wet granulation method. Tablets were subjected to evaluation by studying parameter like hardness, friability, drug content uniformity, and in-vitro drug release. In vitro drug release was evaluated using simulated stomach, intestinal and colonic fluids. The susceptibility of guar gum to colonic bacteria was also assessed by a drug release study with rat caecal contents. The 40% guar gum containing formulation (F-1) showed better drug release (91.1%) after 24 hours in the presence of rat caecal contents in comparison with the 50% guar gum containing formulation (F-2) (82.1%). Curcumin could, thus, be positively delivered to the colon for effective colon cancer treatment using guar gum.

  2. Nutrients and Risk of Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Jinfu, E-mail: Jinfu.hu@phac-aspc.gc.ca [Evidence and Risk Assessment Division, Centre for Chronic Disease Prevention and Control, Public Health Agency of Canada, 785 Carling Avenue, AL: 6807B, Ottawa, Ontario K1A 0K9 (Canada); La Vecchia, Carlo [Istituto di Ricerche Farmacologiche “Mario Negri,” Via La Masa, 19-20156 Milan (Italy); Istituto di Statistica Medica e Biometria, Università degli Studi di Milano, Via Venezian, 1, 20133 Milan (Italy); Negri, Eva [Istituto di Ricerche Farmacologiche “Mario Negri,” Via La Masa, 19-20156 Milan (Italy); Mery, Les [Evidence and Risk Assessment Division, Centre for Chronic Disease Prevention and Control, Public Health Agency of Canada, 785 Carling Avenue, AL: 6807B, Ottawa, Ontario K1A 0K9 (Canada)

    2010-02-10

    Dietary fats are thought to be important in the etiology of colon cancer. However, the evidence linking them is inconclusive. Studies on dietary protein, cholesterol and carbohydrate and the risk of colon cancer are also inconsistent. This study examined the association between dietary intake of protein, fats, cholesterol and carbohydrates, and the risk of colon cancer. Mailed questionnaires were completed by 1731 individuals with histologically confirmed cases of colon cancer and 3097 population controls between 1994 and 1997 in seven Canadian provinces. Measurements included socio-economic status, lifestyle habits and diet. A 69-item food frequency questionnaire was used to provide data on eating habits from two years before the study. Odds ratios (OR) and 95% confidence intervals (CI) were computed using unconditional logistic regression. The nutrients were categorized by quartiles based on the distributions among the controls. Intake of polyunsaturated fat, trans-fat and cholesterol were significantly associated with the risk of colon cancer; the ORs for the highest quartiles were 1.36 (95% CI, 1.02–1.80), 1.37 (95% CI, 1.10–1.71) and 1.42 (95% CI, 1.10–1.84), respectively. The association was stronger with proximal colon cancer (PCC). An increased risk was also observed with increasing intake of sucrose for both proximal and distal colon cancers; the ORs for the highest quartiles were 1.67 (95% CI, 1.22–2.29) for PCC and 1.58 (95% CI, 1.18–2.10) for distal colon cancer (DCC). An elevated risk of PCC was also found with increased lactose intake. Our findings provide evidence that a diet low in fat and sucrose could reduce the risk of various colon cancers.

  3. CT findings of early right colonic diverticulitis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Hwa; Ham, Su Yeon; Whang, Kang Ik [Ulsan University Hospital, Ulsan (Korea, Republic of)

    1998-05-01

    The purpose of this study is to investigate the CT findings of acute right colonic diverticulitis, and to determine the difference between these and published reports describing left colonic, especially sigmoid, diverticulitis. Inflamed diverticula were visible in all cases, and were solitary. Nine cases occurred in the ascending colon and four in the cecum; in particular, eleven occurred around the ileocecal valve. In three cases, the inflamed diverticulum was less than 1 cm in diameter; in five cases, 1-2 cm; in three, 2-3 cm, and in two, 3-4 cm. These were able to be classified into two major forms. In three cases it was nodular with hyperattenuation and some inhomogeneity, and ten shows the target form with thick walls and a central cavity. In five of these target lesions, the wall pattern was partially or completely inhomogeneous, or multilayered. The material filling the central cavity were gas in five cases, fecalith in two, and fluid in three. Abnormal pericoloic fat infiltrations were seen in twelve cases (92%), segmental colonic wall thickening in eleven (85%), other not-inflamed diverticula in five (38%), mesenteric lymph node enlargement in three (23%), free pericecal fluid collection in three (23%), and perirenal fascial thickening in two (15%). The complications such as remote abscess cavity, colonic obstruction, fistula or perforation were not found. On barium colon study, diverticulitis was in all cases confirmed by the presence of barium in the deformed diversiculum. Among CT findings for acute right colonic diverticulitis, the most important and pathognomonic is inflamed diverticula; the forms of these vary, and include gangrenous diverticulitis. The CT findings of early right colonic diverticulitis in Koreans might not, however, reveal the complications which sigmoid diverticulitis frequently involves; in patients with right lower quadrant pain imaging studies are performed promptly, and for the mesentery, the anatomical base between right and

  4. Anaerobic bacteria, the colon and colitis.

    Science.gov (United States)

    Roediger, W E

    1980-02-01

    Anaerobic bacteria constitute more than 90% of the bacteria in the colon. An anaerobic environment is needed to maintain their growth and the production of short-chain fatty acids by these bacteria from carbohydrates. Short-chain fatty acids are rapidly absorbed and essential for metabolic as well as functional welfare of the colonic mucosa. The importance of these acids in water absorption and in the patogenesis of colitis is discussed in relation to the concept of "energy deficiency diseases" of the colonic mucosa.

  5. Giant ascending colonic diverticulum presenting with intussusception.

    Science.gov (United States)

    Kim, Ho Jin; Kim, Jin Ha; Moon, Ok In; Kim, Kyung Jong

    2013-10-01

    Diverticular disease of the colon is a common disease, and its incidence is increasing gradually. A giant colonic diverticulum (GCD) is a rare entity and is defined as a diverticulum greater than 4 cm in size. It mainly arises from the sigmoid colon, and possible etiology is a ball-valve mechanism permitting progressive enlargement. A plain abdominal X-ray can be helpful to make a diagnosis initially, and a barium enema and abdominal computed tomography may confirm the diagnosis. Surgical intervention is a definite treatment for a GCD. We report a case of an ascending GCD presenting with intussusception in a young adult.

  6. The bacterial genotoxicity test:issues to be considered in the performance of the test and their recent advances

    Institute of Scientific and Technical Information of China (English)

    HakuA

    2002-01-01

    The bacterial genotoxicity test is widely used as an initial screening to determing the genotoxic potential of chemicals for hazard identification.Firstly,I will state about technical issues in the performance of the test,which may largely affect the results of the mutagenicity of test compounds of lead to low concordance with the results between inter-and intra-laboratories.The second issue of my speech will be a brief review on bacterial tester strains that are highly sensitive to the mutagenicity of particular classes of mutagens.These strains are often used to efficiently explore environmental mutagens and to study the mechanisms of mutagenesis.Finally,I will present our recent study on the use of human S9 fractions in the genotoxicity tests to comprehensively evaluate the genotoxic effect to humans.In addition,genetically-engineered tester strains expressing human drug-metabolizing enzymes will be introduced.

  7. Comparison of the in vivo and in vitro genotoxicity of glyphosate isopropylamine salt in three different organisms

    Directory of Open Access Journals (Sweden)

    Carlos Alvarez-Moya

    2014-01-01

    Full Text Available There is considerable controversy with regard to the genotoxicity of glyphosate, with some reports stating that this compound is non-toxic for fish, birds and mammals. In this work, we used the comet assay to examine the genotoxicity of glyphosate isopropylamine (0.7, 7, 70 and 700 µM in human lymphocytes, erythrocytes of Oreochromis niloticus and staminal nuclei of Tradescantia (4430 in vitro and in vivo. Cells, nuclei and fish that had and had not been exposed to 5 mM N-nitrosodiethylamine (NDEA were used as positive and negative controls, respectively. Significant (p 7 µM, whereas in vitro, glyphosphate was genotoxic in human lymphocytes and Tradescantia hairs at > 0.7 µM. These results indicate that glyphosate is genotoxic in the cells and organisms studied at concentrations of 0.7-7 µM.

  8. State of the Art High-Throughput Approaches to Genotoxicity: Flow Micronucleus, Ames II, GreenScreen and Comet

    Science.gov (United States)

    State of the Art High-Throughput Approaches to Genotoxicity: Flow Micronucleus, Ames II, GreenScreen and Comet (Presented by Dr. Marilyn J. Aardema, Chief Scientific Advisor, Toxicology, Dr. Leon Stankowski, et. al. (6/28/2012)

  9. Therapeutic efficacies of Coriandrum sativum aqueous extract against metronidazole-induced genotoxicity in Channa punctatus peripheral erythrocytes.

    Science.gov (United States)

    Talapatra, Soumendra Nath; Dasgupta, Subham; Guha, Gunjan; Auddy, Moumita; Mukhopadhyay, Aniruddha

    2010-12-01

    Metronidazole (MTZ), a nitroimidazole drug, is primarily used as an anti-protozoan or an anti-bacterial agent in humans, although its genotoxic and carcinogenic effects have been widely reported, particularly in aquatic organisms. MTZ may induce DNA damages through single-strand breaks, modification of bases, DNA-DNA and DNA-protein cross-links, ultimately leading to apoptosis or necrosis. Here, we have assessed the genotoxicity of MTZ in the peripheral erythrocytes of Channa punctatus, using micronucleation (MN) and binucleation (BN) as genotoxicity markers. The therapeutic potential of aqueous extract of Coriandrum sativum against MTZ-induced genotoxicity has also been examined. The results show significant (Psativum leaf extract. Hence, we establish that MTZ can produce considerable degrees of micronucleus and binucleus formation in peripheral erythrocytes of C. punctatus, and such deleterious effect of MTZ treatment can be mitigated by aqueous extract of C. sativum leaves.

  10. A two-level approach towards semantic colon segmentation: removing extra-colonic findings.

    Science.gov (United States)

    Lu, Le; Wolf, Matthias; Liang, Jianming; Dundar, Murat; Bi, Jinbo; Salganicoff, Marcos

    2009-01-01

    Computer aided detection (CAD) of colonic polyps in computed tomographic colonography has tremendously impacted colorectal cancer diagnosis using 3D medical imaging. It is a prerequisite for all CAD systems to extract the air-distended colon segments from 3D abdomen computed tomography scans. In this paper, we present a two-level statistical approach of first separating colon segments from small intestine, stomach and other extra-colonic parts by classification on a new geometric feature set; then evaluating the overall performance confidence using distance and geometry statistics over patients. The proposed method is fully automatic and validated using both the classification results in the first level and its numerical impacts on false positive reduction of extra-colonic findings in a CAD system. It shows superior performance than the state-of-art knowledge or anatomy based colon segmentation algorithms.

  11. Comparison of in vitro cytotoxicity and genotoxicity of MMA-based polymeric materials and various metallic materials

    OpenAIRE

    İZ, Sultan GÜLÇE; GÜRHAN, Saime İsmet DELİLOĞLU; ŞEN, Bilge Hakan

    2010-01-01

    To determine the in vitro cytotoxicity and genotoxicity of some polymeric and metallic implant materials used as base materials in dentistry, based on ISO (International Organization for Standardization) and OECD (Organization for Economic Co-Operation and Development) test protocols. Materials and methods: Three different acrylate-based polymeric materials were tested for their in vitro cytotoxicity and genotoxicity (polymethylmethacrylate microspheres [PMMA], a solid cement prepared by mi...

  12. Genotoxic Effect of Chronic Exposure to DDT on Lymphocytes, Oral Mucosa and Breast Cells of Female Rats

    OpenAIRE

    Ruth De Celis; Ulises Gómez-Pinedo; Hugo Salado-Ponce; Alfredo Feria-Velasco; Alejandro Canales-Aguirre; Eduardo Padilla-Camberos

    2011-01-01

    The genotoxicity of some environmental contaminants may affect human health directly by damaging genetic material and thus plays an important role in cancer development. Xenoestrogens are one kind of environmental pollutants that may alter hormonal routes or directly affect DNA. The number of available biomarkers used to assess genetic risk and cancer is very extensive. The present study evaluated genotoxicity produced by the pesticide DDT on systemic and mammary gland cells obtained from adu...

  13. Drugs Approved for Colon and Rectal Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for use in colon cancer and rectal cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  14. Giant colonic diverticulum: radiographic and MDCT characteristics.

    Science.gov (United States)

    Zeina, Abdel-Rauf; Mahamid, Ahmad; Nachtigal, Alicia; Ashkenazi, Itamar; Shapira-Rootman, Mika

    2015-12-01

    Giant colonic diverticulum (GCD), defined as a diverticulum larger than 4 cm, is a rare entity that is generally a manifestation of colonic diverticular disease. Because of its rarity and its variable and non-specific presentation, the diagnosis of GCD depends mainly on imaging findings. Knowledge of the spectrum of radiographic and CT features of the GCD is important in making the correct diagnosis and potentially preventing complications. This review focuses on imaging findings characteristic of GCD as well as its complications and radiographic mimics. Teaching points • Giant colonic diverticulum is a rare complication of diverticulosis.• The most common symptom is abdominal pain presenting in approximately 70 % of patients.• Diagnosis is based on imaging findings with plain abdominal radiographs and MDCT.• Treatment consists of en bloc resection of the diverticulum and affected adjacent colon.

  15. Preventing Second Cancers in Colon Cancer Survivors

    Science.gov (United States)

    In this phase III trial, people who have had curative surgery for colon cancer will be randomly assigned to take sulindac and a placebo, eflornithine and a placebo, both sulindac and eflornithine, or two placebo pills for 36 months.

  16. Colon Cancer Risk Assessment - Gauss Program

    Science.gov (United States)

    An executable file (in GAUSS) that projects absolute colon cancer risk (with confidence intervals) according to NCI’s Colorectal Cancer Risk Assessment Tool (CCRAT) algorithm. GAUSS is not needed to run the program.

  17. Redefining Adjuvant Therapy for Colon Cancer

    Science.gov (United States)

    In this trial, patients with resected stage III colon cancer are being randomly assigned to receive FOLFOX chemotherapy for either 3 or 6 months and to take either a pill called celecoxib or a matching placebo pill for 3 years.

  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. Comet assay evaluation of six chemicals of known genotoxic potential in rats.

    Science.gov (United States)

    Hobbs, Cheryl A; Recio, Leslie; Streicker, Michael; Boyle, Molly H; Tanaka, Jin; Shiga, Atsushi; Witt, Kristine L

    2015-07-01

    As a part of an international validation of the in vivo rat alkaline comet assay (comet assay) initiated by the Japanese Center for the Validation of Alternative Methods (JaCVAM) we examined six chemicals for potential to induce DNA damage: 2-acetylaminofluorene (2-AAF), N-nitrosodimethylamine (DMN), o-anisidine, 1,2-dimethylhydrazine dihydrochloride (1,2-DMH), sodium chloride, and sodium arsenite. DNA damage was evaluated in the liver and stomach of 7- to 9-week-old male Sprague Dawley rats. Of the five genotoxic carcinogens tested in our laboratory, DMN and 1,2-DMH were positive in the liver and negative in the stomach, 2-AAF and o-anisidine produced an equivocal result in liver and negative results in stomach, and sodium arsenite was negative in both liver and stomach. 1,2-DMH and DMN induced dose-related increases in hedgehogs in the same tissue (liver) that exhibited increased DNA migration. However, no cytotoxicity was indicated by the neutral diffusion assay (assessment of highly fragmented DNA) or histopathology in response to treatment with any of the tested chemicals. Therefore, the increased DNA damage resulting from exposure to DMN and 1,2-DMH was considered to represent a genotoxic response. Sodium chloride, a non-genotoxic non-carcinogen, was negative in both tissues as would be predicted. Although only two (1,2-DMH and DMN) out of five genotoxic carcinogens produced clearly positive results in the comet assay, the results obtained for o-anisidine and sodium arsenite in liver and stomach cells are consistent with the known mode of genotoxicity and tissue specificity exhibited by these carcinogens. In contrast, given the known genotoxic mode-of-action and target organ carcinogenicity of 2-AAF, it is unclear why this chemical failed to convincingly increase DNA migration in the liver. Thus, the results of the comet assay validation studies conducted in our laboratory were considered appropriate for five out of the six test chemicals.

  20. Colon cancer presented with sigmoid volvulus: A case report

    Directory of Open Access Journals (Sweden)

    Abbas Aras

    2015-01-01

    Conclusion: When surgery is performed due to the urgent colonic obstruction in colonic volvulus diagnosed patients, a colon tumour should be considered in the same column loops or in the distal colon. We believe that CT is the method that should be preferred in large-bowel obstruction suspected patients.

  1. Triclosan promotes Staphylococcus aureus nasal colonization.

    Science.gov (United States)

    Syed, Adnan K; Ghosh, Sudeshna; Love, Nancy G; Boles, Blaise R

    2014-04-08

    The biocide triclosan is used in many personal care products, including toothpastes, soaps, clothing, and medical equipment. Consequently, it is present as a contaminant in the environment and has been detected in some human fluids, including serum, urine, and milk. Staphylococcus aureus is an opportunistic pathogen that colonizes the noses and throats of approximately 30% of the population. Colonization with S. aureus is known to be a risk factor for several types of infection. Here we demonstrate that triclosan is commonly found in the nasal secretions of healthy adults and the presence of triclosan trends positively with nasal colonization by S. aureus. We demonstrate that triclosan can promote the binding of S. aureus to host proteins such as collagen, fibronectin, and keratin, as well as inanimate surfaces such as plastic and glass. Lastly, triclosan-exposed rats are more susceptible to nasal colonization with S. aureus. These data reveal a novel factor that influences the ability of S. aureus to bind surfaces and alters S. aureus nasal colonization. IMPORTANCE Triclosan has been used as a biocide for over 40 years, but the broader effects that it has on the human microbiome have not been investigated. We demonstrate that triclosan is present in nasal secretions of a large portion of a test population and its presence correlates with Staphylococcus aureus nasal colonization. Triclosan also promotes the binding of S. aureus to human proteins and increases the susceptibility of rats to nasal colonization by S. aureus. These findings are significant because S. aureus colonization is a known risk factor for the development of several types of infections. Our data demonstrate the unintended consequences of unregulated triclosan use and contribute to the growing body of research demonstrating inadvertent effects of triclosan on the environment and human health.

  2. Osteopathic manipulative treatment for colonic inertia.

    Science.gov (United States)

    Cohen-Lewe, Adam

    2013-03-01

    Surgical treatment options for patients with colonic inertia are costly and do not always relieve the pain associated with the condition. The author describes a case of a 41-year-old woman with colonic inertia who received osteopathic manipulative treatment targeted at the neuromusculoskeletal and gastrointestinal systems. The patient reported temporary improvement in pain and bowel function without pharmacotherapy or surgical intervention. Osteopathic manipulative treatment should be considered in patients with visceral as well as neuromusculoskeletal symptoms.

  3. Eosinophilic gastroenteritis with ascites and colon involvement.

    Science.gov (United States)

    Levinson, J D; Ramanathan, V R; Nozick, J H

    1977-12-01

    The case of a 39-year old white man with eosinophilic gastroenteritis is presented. The major clinical features were gastric outlet obstruction, diarrhea and massive ascites. At surgery, significant involvement of the entire gastrointestinal tract from the gastric antrum to the sigmoid colon was found. Histologic documentation of colon involvement was obtained. The response to corticosteroids was prompt and sustained. At present, he is maintained on an alternating day schedule of steroid administration.

  4. Lead-induced genotoxicity to Vicia faba L. roots in relation with metal cell uptake and initial speciation.

    Science.gov (United States)

    Shahid, M; Pinelli, E; Pourrut, B; Silvestre, J; Dumat, C

    2011-01-01

    Formation of organometallic complexes in soil solution strongly influence metals phytoavailability. However, only few studies deal with the influence of metal speciation both on plant uptake and genotoxicity. In the present study, Vicia faba seedlings were exposed for 6h in controlled hydroponic conditions to 5 μM of lead nitrate alone and chelated to varying degrees by different organic ligands. Ethylenediaminetetraacetic acid and citric acid were, respectively, chosen as models of humic substances and low weight organic acids present in natural soil solutions. Visual Minteq software was used to estimate free lead cations concentration and ultimately to design the experimental layout. For all experimental conditions, both micronucleus test and measure of lead uptake by plants were finally performed. Chelation of Pb by EDTA, a strong chelator, dose-dependently increased the uptake in V. faba roots while its genotoxicity was significantly reduced, suggesting a protective role of EDTA. A weak correlation was observed between total lead concentration absorbed by roots and genotoxicity (r(2)=0.65). In contrast, a strong relationship (r(2)=0.93) exists between Pb(2+) concentration in exposure media and genotoxicity in the experiment performed with EDTA. Citric acid induced labile organometallic complexes did not demonstrate any significant changes in lead genotoxicity or uptake. These results demonstrate that metal speciation knowledge could improve the interpretation of V. faba genotoxicity test performed to test soil quality.

  5. Analysis of 75 marketed pharmaceuticals using the GADD45a-GFP 'GreenScreen HC' genotoxicity assay.

    Science.gov (United States)

    Hastwell, Paul W; Webster, Thomas W; Tate, Matthew; Billinton, Nicholas; Lynch, Anthony M; Harvey, James S; Rees, Robert W; Walmsley, Richard M

    2009-09-01

    The GADD45a-GFP (GreenScreen HC) reporter assay detects genotoxic damage in the human lymphoblastoid TK6 cell line and gives positive results for all classes of genotoxin, including mutagens, aneugens and clastogens. In this study, a collection of 75 marketed pharmaceuticals were tested in the assay. Compounds in the collection represent a broad range of chemical structures, pharmacologies and therapeutic indications, including neoplasia and viral infection where positive genotoxicity results are often associated with the pharmacological activity. Based on the results of this study, two main conclusions can be drawn: (i) the GreenScreen HC is more predictive of in vivo genotoxicity (88%) and genotoxic carcinogenicity (93%) data than the any of the other regulatory in vitro genotoxicity assay and (ii) no compounds were uniquely positive in the GADD45a-GFP assay. This analysis therefore provides additional evidence to support the use of the GADD45a-GFP assay as an effective tool either in early genotoxic liability identification or non-clinical safety assessment of candidate pharmaceuticals during development.

  6. Effects of morphine and naloxone on feline colonic transit

    Energy Technology Data Exchange (ETDEWEB)

    Krevsky, B.; Libster, B.; Maurer, A.H.; Chase, B.J.; Fisher, R.S.

    1989-01-01

    The effects of endogenous and exogenous opioid substances on feline colonic transit were evaluated using colonic transit scintigraphy. Naloxone accelerated emptying of the cecum and ascending colon, and filling of the transverse colon. Endogenous opioid peptides thus appear to play a significant role in the regulation of colonic transit. At a moderate dose of morphine cecum and ascending colon transit was accelerated, while at a larger dose morphine had no effect. Since naloxone, a relatively nonspecific opioid antagonist, and morphine, a principally mu opioid receptor agonist, both accelerate proximal colonic transit, a decelerating role for at least one of the other opioid receptors is inferred.

  7. Endoscopic polypectomy in treatment of colon adenomatosis

    Directory of Open Access Journals (Sweden)

    Chalyk Yu.V.

    2012-03-01

    Full Text Available Objective: To study the value of endoscopic polypectomy in the treatment of family adenomatous polyposis of the colon. Materials and methods. A total of 7 patients with diffuse adenomatosis of the colon family, who were treated at the proctological department of Hospital № 8 in Saratov from 2004 to 2006 on the stage of diagnosis all patients underwent double-contrast irrigoscopy and fibrocolonoscopy with biopsy. Endoscopic removal of polyps performed by electroscission through fibrocolonoscope «Olympus CF-E3 L» with a standard loop diathermy and electrosurgical apparatus «Endothelial-1». Results. Total rehabilitation after endoscopic polyp from retained sections of the colon and adequate comprehensive preoperative patients are routinely carried out successfully three right-left-sided hemicolec-tomy and 4 on the diffuse polyposis of the colon, complicated by recurrent bleeding or malignancy of polyps. Conclusion. Non-radical surgery in combination with endoscopic polypectomy does not relieve the patient diffuse polyposis of the colon family of high risk of colorectal cancer. In the case of diffuse polyposis, endoscopic polypectomy family is of limited value, as not able to eliminate completely a potential substrate of the disease, which is the entire mucosa of the colon

  8. Genotoxic effects of 2-dodecyl cyclobutanone; Genotoxizitaet von 2-Dodecylcyclobutanon

    Energy Technology Data Exchange (ETDEWEB)

    Delincee, H.; Pool-Zobel, B.L.; Rechkemmer, G. [Bundesforschungsanstalt fuer Ernaehrung, Karlsruhe (Germany). Inst. fuer Ernaehrungsphysiologie

    1999-07-01

    The paper reports in vivo experiments with rats who received two different doses of 2-dodecyl cyclobutane administered orally. 16 hours after administration, colon cells were isolated and examined for DNA damage by means of the comet assay. No cytotoxic effects were found with the trypan blue exclusion test. When the '% tail intensity' or the 'tail moment' were used for quantitative analysis with the comet assay, it was found that similar results are obtained for the test group which received a lower dose of 2-dodecyl cyclobutane (1.12 mg/kg of body weight) and the control group which received 2% dimethyl sulfoxide. Administration of higher concentrations of the 2-dodecyl cyclobutane (14.9 mg/kg of body weight) was found to induce minor, but significant DNA damage in the test group. Further experiments will be needed in order to assess the relevance of these results for assessment of health risks due to consumption of irradiated food. (orig./CB) [German] In dieser Arbeit wurden in vivo-Versuche an Ratten, die zwei Dosierungen an 2-Dodecylcyclobutanon per Schlundsonde erhielten, durchgefuehrt. Nach 16-stuendiger Einwirkung wurden Kolonzellen aus den Ratten isoliert und mit Hilfe des Comet Assay auf DNA-Schaeden analysiert. Zytotoxische Effekte wurden bei der Anwendung des Trypanblau-Ausschlusstests nicht festgestellt. Wenn im Comet Assay zur quantitativen Auswertung das '% tail intensity' oder das 'tail moment' eingesetzt wurde, wurde bei der Versuchsgruppe, die eine niedrigere Konzentration des 2-Dodecylcyclobutanons (1,12 mg/kg Koerpergewicht) erhielt, aehnliche Werte wie bei der Kontrollgruppe, die 2% Dimethylsulfoxid verabreicht bekamen, beobachtet. Bei der hoeheren Konzentration des 2-Dodecylcyclobutanons (14,9 mg/kg Koerpergewicht) wurde in der Versuchsgruppe eine geringe, aber signifikante DNA-Schaedigung festgestellt. Weiterfuehrende Untersuchungen sind erforderlich, um die Relevanz dieser Ergebnisse fuer eine

  9. Ambivalent colonal relations in octavia butler’s wild seed

    OpenAIRE

    Thamer Amer Jubouri Al Ogaili; Ruzbeh Babaee

    2016-01-01

    This article explores postcolonial powers of ambivalence in Octavia Butler’s Wild Seed (1980). It will offer an in-depth analysis of the thematic and ideological characteristics of selected work. We will mainly focus on the theme of the mutual relationship between the colonized and the colonizer in the novel. This relationship is specified to the concept of ambivalence that incarnates the dual, yet, uncontrolled relationship between the colonized and the colonizer. Nevertheless, the colonized...

  10. Genotoxicity of SPL (spent pot lining) as measured by Tradescantia bioassays.

    Science.gov (United States)

    Andrade-Vieira, L F; Davide, L C; Gedraite, L S; Campos, J M S; Azevedo, H

    2011-10-01

    Spent Pot Liner (SPL) is a solid waste product generated in the process of aluminum production. Tradescantia micronuclei (Trad-MN) and stamen hair mutation (Trad-SHM) bioassays are very useful tests to assess genotoxicity of environmental pollutants. In the present study, we intended to investigate the genotoxicity of this waste with Tradescantia bioassays using leachates of SPL simulating the natural leachability of SPL in soil. The formation of micronuclei (MN) was found to be concentration dependent. MN frequency enhanced significantly with SPL treatment. In addition, SPL also appeared to increase the percentage of dyads and triads. Trad-SHM assay showed that SPL increases pink mutation events as SPL concentration increases. These results demonstrated that SPL is a cytogenotoxic agent that affects different genetic end-points (induction of micronuclei and point mutations) even at low concentration (2% and 3%).

  11. Genotoxicity studies in vitro and in vivo on carminic acid (natural red 4).

    Science.gov (United States)

    Loprieno, G; Boncristiani, G; Loprieno, N

    1992-09-01

    The potential genotoxic activity of carminic acid (CAS no. 1260-17-9; EINECS no. 215-023-3; C.I. no. 75410), a component of natural red colouring products (cochineal: CAS no. 1343-78-8; EINECS no. 215-680-6; C.I. no. 75470), used in food, cosmetics and drugs, has been evaluated by means of a series of short-term tests in vitro and in vivo, namely Salmonella reverse mutation, chromosome aberrations and sister chromatid exchanges in vitro on Chinese hamster ovary cells, and the mouse micronucleus test. All studies have produced negative results. The data obtained strongly support the non-mutagenic/non-carcinogenic activity of this compound. Genotoxicity data previously obtained for carminic acid, concerning the induction of a series of other genetic endpoints in different test systems, have also been considered, as have recent findings that indicate lack of carcinogenic activity in the cochineal preparation containing 29.8% carminic acid.

  12. Genotoxicity of tetrodotoxin from puffer fish tested in root meristem cells of Allium cepa L.

    Science.gov (United States)

    Khora, S S; Panda, K K; Panda, B B

    1997-07-01

    Tetrodotoxin (TTX) extracted and purified from puffer fish Arothron nigropunctatus was tested for genotoxicity employing the root meristem cells of Allium cepa as the assay system. The genotoxicity endpoints investigated were mitotic index (MI), meta-anaphases with spindle aberrations, interphases with micronuclei (MNC) and sister chromatid exchanges (SCE) in metaphase chromosomes. The results demonstrated that TTX inhibited mitosis at concentrations of > or = 30 microM as evident by the fall of MI, but failed to induce MNC at significant levels at any of the concentrations tested (10-100 microM). TTX was thus proved to be neither clastogenic nor aneugenic in the present study. It was, however, noteworthy that TTX at far lower concentrations, 0.1-5.0 microM, significantly enhanced the frequencies of SCE which indicated possible interference of the toxin in DNA replication and repair.

  13. The in vitro and in vivo genotoxicity of benzocaine: a brief communication.

    Science.gov (United States)

    Brock, William J; Bell, Thomas A

    2012-06-01

    Benzocaine has a long history of use in human medicine. However, benzocaine also has been used in aquaculture with finfish for more than 40 years for sedating fish for marking, transport, surgery, and so on, although benzocaine does not have a current Food and Drug Administration (FDA) approval for this application in the United States. As part of a FDA approval for use as an animal drug, the genotoxicity of benzocaine was evaluated in the in vitro bacterial reverse mutation assay and the forward mutation assay and in vivo in the mouse micronucleus assay. These studies were conducted in compliance with Good Laboratory Practice regulations and according to Veterinary International Conference on Harmonisation guidelines. Based on the results of these studies, benzocaine was determined not to be genotoxic.

  14. Observations of the effect of atmospheric processes on the genotoxic potency of airborne particulate matter

    DEFF Research Database (Denmark)

    Feilberg, Anders; Nielsen, Torben; Binderup, Mona-Lise

    2002-01-01

    In this study, the relationship between genotoxic potency and the occurrence of polycyclic aromatic hydrocarbons (PAH), including benzo(a)pyrene (BaP), and nitro-PAH in urban and semi-rural air masses has been investigated. The Salmonella/microsome assay has been used as a measure of genotoxic...... potency. We find that the ratios of BaP/ mutagenicity and PAH/mutagenicity are highly variable. The processes responsible for the variation are formation and degradation of mutagens and transport of polluted air masses from heavily industrialized regions, Air masses from Central Europe are shown...... been used in the past as an indicator of the carcinogenic risk of airborne particles, it is suggested that the cancer risk of air pollution has to be re-evaluated....

  15. Assessment of in vitro genotoxic and cytotoxic effects of flurbiprofen on human cultured lymphocytes.

    Science.gov (United States)

    Timocin, Taygun; Ila, Hasan Basri; Dordu, Tuba; Husunet, Mehmet Tahir; Tazehkand, Mostafa Norizadeh; Valipour, Ebrahim; Topaktas, Mehmet

    2016-01-01

    Flurbiprofen is non-steroidal anti-inflammatory drug which is commonly used for its analgesic, antipyretic, and anti-inflammatory effects. The purpose of the study was to explore the genotoxic and cytotoxic effects of flurbiprofen in human cultured lymphocytes by sister chromatid exchange, chromosome aberration, and cytokinesis-blocked micronucleus tests. 10, 20, 30, and 40 μg/mL concentrations of flurbiprofen (solvent is DMSO) were used to treatment of human cultured lymphocytes at two different treatment periods (24 and 48 h). Flurbiprofen had no significant genotoxic effect in any of these tests. But exposing to flurbiprofen for 24 and 48 h led to significant decrease on proliferation index, mitotic index, and nuclear division index (NDI). Also, all decreases were concentration-dependent (except NDI at 24 h treatment period). Consequently, the findings of this research showed that flurbiprofen had cytotoxic effects in human blood lymphocytes.

  16. Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity

    DEFF Research Database (Denmark)

    Poulsen, Sarah S.; Jackson, Petra; Kling, Kirsten;

    2016-01-01

    Lung deposition of multi-walled carbon nanotubes (MWCNT) induces pulmonary toxicity. Commercial MWCNT vary greatly in physicochemical properties and consequently in biological effects. To identify determinants of MWCNT-induced toxicity, we analyzed the effects of pulmonary exposure to 10 commercial...... MWCNT on day 28 and 92. Using adjusted, multiple regression analyses, inflammation and genotoxicity were related to dose, time and physicochemical properties. The specific surface area (BET) was identified as a positive predictor of pulmonary inflammation on all post-exposure days. In addition, length...... diameter was associated with increased genotoxicity. This study provides information on possible toxicity-driving physicochemical properties of MWCNT. The results may contribute to safe-by-design manufacturing of MWCNT, thereby minimizing adverse effects....

  17. Cytotoxic, mutagenic and genotoxic evaluation of crude extracts and fractions from Piper jericoense with trypanocidal action.

    Science.gov (United States)

    Hamedt, A L; Ortiz, I C; García-Huertas, P A; Sáenz, J; de Araujo, A Caldeira; De Mattos, J C P; Rodríguez-Gazquez, M A; Triana-Chávez, O

    2014-03-01

    The current Chagas disease treatment is based on two drugs, nifurtimox and benznidazole, which is considered unsatisfactory, not only because of the narrow therapeutic range but also because of the associated toxicity. Natural products are considered an important source of biologically active compounds against various infectious organisms. Numerous Piper species are used in traditional medicine to treat parasitic diseases. In this paper, we study the activity of extracts and fractions obtained from Piper jericoense plant against epimastigote, trypomastigote and amastigote forms of Trypanosoma cruzi. In addition, we evaluated the cytotoxic, mutagenic and genotoxic activities of the F4 fraction obtained from one of the more promising extracts. We obtained four extracts, one of which presented low toxicity and high trypanocidal activity. This extract was separated into eight fractions, and the F4 fraction presented better results than the other extracts and had a higher selectivity index than the reference drug, benznidazole. This fraction was not cytotoxic, mutagenic or genotoxic.

  18. Genotoxic effects of linear alkyl benzene sulfonate, sodium pentachlorophenate and dichromate on Tetrahymena pyriformis.

    Science.gov (United States)

    Wu, Y; Shen, Y

    1992-01-01

    DNA in macro- and micronuclei of Tetrahymena pyriformis treated with linear alkyl benzene sulfonate (LAS) and sodium pentachlorophenate (PCP-Na) were determined by microspectrophotometry. The effects on rate of formation of macronuclear DNA extrusion bodies were also studied. We found DNA content of micronuclei in 0.14 ppm LAS and 0.9 ppb PCP-Na was lower than in that of the control, and LAS was able to increase the formation rate of macronuclear DNA extrusion bodies (the formation rate was 54% in 11.3 ppm LAS and 25.6% in 16.7 ppm dichromate). We concluded that 0.14 ppm LAS (below the maximum acceptable toxicant concentration) was genotoxic, whereas 0.014 ppm LAS was not. Dichromate 0.05 ppm and 0.9 ppb PCP-Na, equal to and below the maximum acceptable toxicant concentration, respectively, were potentially genotoxic.

  19. Evaluation of the genotoxicity and cytotoxicity of semipurified fractions from the Mediterranean brown algae, Dictyopteris membranacea

    Directory of Open Access Journals (Sweden)

    Najoua Akremi

    2016-01-01

    Full Text Available Dictyopteris membranacea, a species of Mediterranean brown algae,is believed to have potential pharmacological and nutritional applications. However, such potentials only make sense when devoid of any adverse health consequences. The present study should be seen in this context. It aimed at evaluating the genotoxicity and cytoxicity of its organic extract (F0 and semi purified fractions (F 4, F 5, and F 6.Extracts were tested using the bacterial Vitotox® test and micronucleus assay in different concentrations (from 1.25 μg/mL up to 100 μg/mL, depending on the test and the extract. Applied concentrations were based on a preliminary dose-finding test with the neutral red uptake assay. The results show that all extracts were not genotoxic in the presence or absence of a rat metabolic enzyme fraction (S9. This is encouraging and justifies further investigations on the therapeutic and other values of this algae.

  20. Modulation of genotoxicity of oxidative mutagens by glycyrrhizic acid from Glycyrrhiza glabra L.

    Directory of Open Access Journals (Sweden)

    Prabhjit Kaur

    2012-01-01

    Full Text Available Background: The chemopreventive effects of certain phytoconstituents can be exploited for their use as functional foods, dietary supplements and even as drugs. The natural compounds, acting as anti-genotoxic and free radical scavenging compounds, may serve as potent chemopreventive agents. These can inhibit DNA modulatory activities of mutagens and help preventing pathological processes. Objectives: Present study on Glycyrrhiza glabra L., a promising medicinal plant, widely used in traditional medicine, focused on the bioassay-guided fractionation of its extracts for the isolation of certain phytochemicals with anti-genotoxic potential against oxidative mutagens. Materials and Methods: The methanol extract of Glycyrrhiza glabra rhizomes was subjected to column chromatography, and isolated fraction was evaluated for its anti-genotoxic and antioxidant potential using SOS chromotest, Comet assay, and DPPH radical scavenging assay. Results: GLG fraction, which was characterized as Glycyrrhizic acid, inhibited the genotoxicity of oxidative mutagens viz., H 2 O 2 and 4NQOquite efficiently. In SOS chromotest, using E.coli PQ37 tester strain, it inhibited induction factor induced by H 2 O 2 and 4NQO by 75.54% and 71.69% at the concentration of 121.46 μM,respectively. In Comet assay, it reduced the tail moment induced by H 2 O 2 and 4NQO by 70.21% and 69.04%, respectively, at the same concentration in human blood lymphocytes. The isolated fraction also exhibited DPPH free radical scavenging activity and was able to scavenge 85.95% radicals at a concentration of 120 μM. Conclusion: Glycyrrhizic acid is a potential modulator of genotoxins as well as efficient scavenger of free radicals.

  1. Electrochemical Genotoxicity Assay Based on a SOS/umu Test Using Hydrodynamic Voltammetry in a Droplet

    OpenAIRE

    Kazuharu Sugawara; Masami Fukushima; Shigeru Taguchi; Noriko Hata; Kazuto Sazawa; Yasuaki Nanayama; Hideki Kuramitz

    2012-01-01

    The SOS/umu genotoxicity assay evaluates the primary DNA damage caused by chemicals from the β-galactosidase activity of S. typhimurium. One of the weaknesses of the common umu test system based on spectrophotometric detection is that it is unable to measure samples containing a high concentration of colored dissolved organic matters, sediment, and suspended solids. However, umu tests with electrochemical detection techniques prove to be a better strategy because it causes less inter...

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

    OpenAIRE

    Amanda L. Gindri; Ana Paula D. Coelho; Solange B. Tedesco; Athayde, Margareth L.

    2015-01-01

    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 quanti...

  3. 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.

  4. 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.

  5. Aroclor 1254 increases the genotoxicity of several carcinogens to liver primary cell cultures

    Energy Technology Data Exchange (ETDEWEB)

    Mendoza-Figueroa, T.; Lopez-Revilla, R.; Villa-Trevino, S.

    1985-01-01

    The genotoxicity of both direct-acting and precarcinogenic chemicals was evaluated in liver primary cell cultures (LPCC) from untreated and Aroclor 1254 (Ar) pretreated rats. Hepatocytes were isolated from partially hepatectomized rats and their DNA was labeled in vitro with (/sup 3/H) dThd; the molecular weight of single-stranded DNA was determined by alkaline sucrose sedimentation. Two parameters of DNA damage were defined: 1) the mean effective dose (ED50), i.e., the carcinogen concentration that decreased the DNA molecular weight to half the original, and 2) the DNA breaking potency (DBP), i.e., the number of breaks per DNA molecule produced by 2 h exposure to 1mM concentration of the chemical. Two hours exposure of LPCC from untreated rats to the direct-acting alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (6.8-340..mu..M) and to the precarcinogens benzo(a)pyrene (BaP) (0.05-0.33 mM) and dimethylnitrosamine (DMN) (0.45-16 mM) produced a concentration-dependent decrease in the molecular weight of DNA. Pretreatment of rats with Ar decreased significantly the sedimentation velocity of DNA and increased five, three, and two times the DBP of MNNG, BaP, and DMN, respectively. These results show that Ar-pretreatment of rats increases the genotoxicity of both direct-acting and precarcinogenic chemicals and suggest that Ar might increase the genotoxicity of chemical carcinogens perhaps by enhancing their metabolic activation, by producing direct genotoxic effects, or both. Our results also emphasize the carcinogenic risk that the environmental pollution by polychlorinated biphenyls might represent to humans.

  6. Aroclor 1254 increases the genotoxicity of several carcinogens to liver primary cell cultures.

    Science.gov (United States)

    Mendoza-Figueroa, T; López-Revilla, R; Villa-Treviño, S

    1985-01-01

    The genotoxicity of both direct-acting and precarcinogenic chemicals was evaluated in liver primary cell cultures (LPCC) from untreated and Aroclor 1254 (Ar) pretreated rats. Hepatocytes were isolated from partially hepatectomized rats and their DNA was labeled in vitro with [3H] dThd; the molecular weight of single-stranded DNA was determined by alkaline sucrose sedimentation. Two parameters of DNA damage were defined: the mean effective dose (ED50), i.e., the carcinogen concentration that decreased the DNA molecular weight to half the original, and the DNA breaking potency (DBP), i.e., the number of breaks per DNA molecule produced by 2 h exposure to 1 mM concentration of the chemical. Two hours exposure of LPCC from untreated rats to the direct-acting alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (6.8-340 microM) and to the precarcinogens benzo[a]pyrene (BaP) (0.05-0.33 mM) and dimethylnitrosamine (DMN) (0.45-16 mM) produced a concentration-dependent decrease in the molecular weight of DNA. Pretreatment of rats with Ar decreased significantly the sedimentation velocity of DNA and increased five, three, and two times the DBP of MNNG, BaP, and DMN, respectively. These results show that Ar-pretreatment of rats increases the genotoxicity of both direct-acting and precarcinogenic chemicals and suggest that Ar might increase the genotoxicity of chemical carcinogens perhaps by enhancing their metabolic activation, by producing direct genotoxic effects, or both. Our results also emphasize the carcinogenic risk that the environmental pollution by polychlorinated biphenyls might represent to humans.

  7. Dimethylnitrosamine genotoxicity in rat liver primary cell cultures with low cytochrome P-450 levels.

    Science.gov (United States)

    Mendoza-Figueroa, T

    1984-12-01

    Liver primary cell cultures (LPCC) with decreasing concentrations of cytochrome P-450 were used to investigate the genotoxicity of the hepatic carcinogen dimethylnitrosamine (DMN) and the correlation between DMN genotoxicity and cytochrome P-450 levels. Hepatocytes were isolated from partially hepatectomized rats and incubated with [3H]thymidine; single-strand DNA molecular weight was determined by alkaline sucrose sedimentation. The molecular weight of DNA decreased 50% in LPCC plated either 2 or 24 h before being treated for 24 h with 70 micron DMN. Cytochrome P-450 content was 188 pmol per mg protein in freshly isolated hepatocytes, whereas it was 70 and 32 pmol per mg protein in hepatocytes that had been cultured 24 and 48 h, respectively. Incorporation of 14C into acid-insoluble material was the same in LPCC exposed 24 h to [14C]DMN starting either 2 or 24 h after cell plating. At non-toxic concentrations (0.01-1 microM), SKF 525-A, an inhibitor of mixed-function oxidase enzymes, inhibited approximately 20% of the binding of 14C from [14C]DMN to acid-insoluble material in LPCC plated either 2 or 24 h before they were exposed to DMN for 24 h. Hepatocyte cultures exposed to the direct-acting alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (at concentrations ranging between 6.8 X 10(-8) and 6.8 X 10(-5) M) starting 2 and 24 h after plating, exhibited significant unscheduled DNA synthesis. These results indicate that DMN genotoxicity was similar in LPCC differing considerably in cytochrome P-450 levels, and they suggest that DMN genotoxicity in these cultures is due mainly to similar DMN activation than to decreased DNA repair.

  8. Analyses of Cytotoxic and Genotoxic Potentials of Loranthus micranthus using the Allium cepa Test

    Directory of Open Access Journals (Sweden)

    B.A. Iwalokun

    2011-09-01

    Full Text Available Loranthus micranthus (LM is one of the Nigerian folk medicinal plants used chronically for the management of immuno-depressive illnesses such as diabetes mellitus, cancer and hypertension. There has not been report on the cytotoxic and genotoxic effects of the plant. This study was conducted to investigate the cytotoxic, mitodepressive and genotoxic effects of LM against Allium cepa root cells. The roots of Allium cepa (onion bulb were exposed to different concentrations (2.5-40 mg/mL of L. micranthus aqueous leaf extract (LMAE using NaN3 (100 ug/mL and distilled water as positive and negative controls and examined macroscopically and microscopically for toxic effects. Phytochemical screening of the plant was also carried out using conventional methods. LMEA was found to significantly (p0.05 at 5 mg/mL compared to the control and did not display significant variation in activity between 20 and 40 mg/mL concentrations respectively (p>0.05. Furthermore, LMAE at 10 mg/mL was found to produce the highest number of aberrant cells but failed to elicit c-mitosis found only at 40 mg/mL. LMAE at 5 mg/mL produced the least number of aberrant cells and also failed to induce micronucleus and binucleated cell formation found mostly at 40 mg/mL. Chromosomal aberrations including stickiness, multipolar anaphase and lagging chromosomes, breaks and bridges were induced by all the extract concentrations tested but not dose-dependently. Tannins, alkaloids, saponins and flavonoids were also present in the extract. Our findings indicate that LM is cytotoxic, mitodepressive and genotoxic to Allium cepa especially at doses beyond pharmacological range in vitro and suggest for safety reasons, the continuous use of this plant at lower concentrations for human phytomedicine coupled with a need to conduct further in vivo genotoxic tests.

  9. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review.

    Science.gov (United States)

    Chappell, Grace; Pogribny, Igor P; Guyton, Kathryn Z; Rusyn, Ivan

    2016-01-01

    Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as "carcinogenic to humans" (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments.

  10. Genotoxic and mutagenic effects of lipid-coated CdSe/ZnS quantum dots.

    Science.gov (United States)

    Aye, Mélanie; Di Giorgio, Carole; Berque-Bestel, Isabelle; Aime, Ahissan; Pichon, Benoit P; Jammes, Yves; Barthélémy, Philippe; De Méo, Michel

    2013-01-20

    We proposed to evaluate the genotoxicity and mutagenicity of a new quantum dots (QDs) nanoplatform (QDsN), consisting of CdSe/ZnS core-shell QDs encapsulated by a natural fusogenic lipid (1,2-di-oleoyl-sn-glycero-3-phosphocholine (DOPC)) and functionalized by a nucleolipid N-[5'-(2',3'-di-oleoyl) uridine]-N',N',N'-trimethylammoniumtosylate (DOTAU). This QDs nanoplatform may represent a new therapeutic tool for the diagnosis and treatment of human cancers. The genotoxic, mutagenic and clastogenic effects of QDsN were compared to those of cadmium chloride (CdCl(2)). Three assays were used: (1) the Salmonella/microsome assay with four tester strains, (2) the comet assay and (3) the micronucleus test on CHO cells. The contribution of simulated sunlight was studied in the three assays while oxidative events were only explored in the comet assay in aliquots pretreated with the antioxidant l-ergothioneine. We found that QDsN could enter CHO-K1 cells and accumulate in cytoplasmic vesicles. It was not mutagenic in the Salmonella/mutagenicity test whereas CdCl(2) was weakly positive. In the dark, both the QDsN and CdCl(2) similarly induced dose-dependent increases in single-strand breaks and micronuclei. Exposure to simulated sunlight significantly potentiated the genotoxic activities of both QDsN and CdCl(2), but did not significantly increase micronucleus frequencies. l-Ergothioneine significantly reduced but did not completely suppress the DNA-damaging activity of QDsN and CdCl(2). The present results clearly point to the genotoxic properties and the risk of long-term adverse effects of such a nanoplatform if used for human anticancer therapy and diagnosis in the future.

  11. 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.

  12. 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.

  13. Assessment of the Genotoxicity of olive mill waste water (OMWW) with the Vicia faba Micronucleus test

    Energy Technology Data Exchange (ETDEWEB)

    El Hajjouji, H.; Pinelli, E.; Revel, J. C.; Hafidi, M.

    2009-07-01

    Olive mill waste water (OMW) can cause serious environmental hazards in olive producing countries, especially around the Mediterranean basin. In Morocco, olive mills are noe of the foremost polluters: the volume of OMW produced annually is estimated at 250 000 m{sup 3} during the season of production. the present study concerns the genotoxicity of OMW generated in mills producing olive oil in Morocco. (Author)

  14. Cytotoxicity and genotoxicity of calcium silicate-based cements on an osteoblast lineage

    Directory of Open Access Journals (Sweden)

    Ana Lívia GOMES-CORNÉLIO

    2016-01-01

    Full Text Available Abstract Several calcium silicate-based biomaterials have been developed in recent years, in addition to Mineral Trioxide Aggregate (MTA. The aim of this study was to evaluate the cytotoxicity, genotoxicity and apoptosis/necrosis in human osteoblast cells (SAOS-2 of pure calcium silicate-based cements (CSC and modified formulations: modified calcium silicate-based cements (CSCM and three resin-based calcium silicate cements (CSCR1 (CSCR 2 (CSCR3. The following tests were performed after 24 hours of cement extract exposure: methyl-thiazolyl tetrazolium (MTT, apoptosis/necrosis assay and comet assay. The negative control (CT- was performed with untreated cells, and the positive control (CT+ used hydrogen peroxide. The data for MTT and apoptosis were submitted to analysis of variance and Bonferroni’s posttest (p < 0.05, and the data for the comet assay analysis, to the Kruskal-Wallis and Dunn tests (p < 0.05. The MTT test showed no significant difference among the materials in 2 mg/mL and 10 mg/mL concentrations. CSCR3 showed lower cell viability at 10 mg/mL. Only CSC showed lower cell viability at 50 mg/mL. CSCR1, CSCR2 and CSCR3 showed a higher percentage of initial apoptosis than the control in the apoptosis test, after 24 hours exposure. The same cements showed no genotoxicity in the concentration of 2 mg/mL, with the comet assay. CSC and CSCR2 were also not genotoxic at 10 mg/mL. All experimental materials showed viability with MTT. CSC and CSCR2 presented a better response to apoptosis and genotoxicity evaluation in the 10 mg/mL concentration, and demonstrated a considerable potential for use as reparative materials.

  15. Cytotoxic and genotoxic potential of surface water from the Pitimbu river, northeastern/RN Brazil

    OpenAIRE

    Lucila Carmem Monte Egito; Maria das Graças Medeiros; Silvia Regina Batistuzzo de Medeiros; Lucymara Fassarella Agnez-Lima

    2007-01-01

    In this study, the onion (Allium cepa) root test was used to evaluate the genotoxicity of the Pitimbu River (Natal city, Brazil) surface water. The water was collected at five sampling sites along the river and one sample was obtained after the treatment (flocculation, chlorination and pH correction) of the river water for human consumption. All raw river water samples increased the frequency of chromosomal abnormalities and/or micronuclei and two of the water samples produced alterations in ...

  16. Evaluation of genotoxic activity of tenofovir disoproxil fumarate in human peripheral lymphocytes

    OpenAIRE

    Kubra Kurt; Lale Donbak; Ahmet Kayraldiz

    2016-01-01

    Purpose: Antiretroviral drugs used in the treatment of HIV (Human Immunodeficiency Virus) iinfection, treat by preventing the proliferation of HIV in human body. People with HIV have to use this drugs for lifelong because of inability of the drugs to eradicate the viruses. In this study, we investigated the in vitro genotoxic activity of tenofovir disoproxil fumarate one of the antiretroviral drugs, in human peripheral lymphocytes. Material and Methods: The cells were treated with four d...

  17. Evaluation of the Genotoxicity and Cytotoxicity of Semipurified Fractions from the Mediterranean Brown Algae, Dictyopteris membranacea

    OpenAIRE

    2016-01-01

    Dictyopteris membranacea, a species of Mediterranean brown algae, is believed to have potential pharmacological and nutritional applications. However, such potentials only make sense when devoid of any adverse health consequences. The present study should be seen in this context. It aimed at evaluating the genotoxicity and cytoxicity of its organic extract (F0) and semi purified fractions (F4, F5, and F6). Extracts were tested using the bacterial Vitotox® test and micronucleus assay in differ...

  18. Resveratrol Modulates the Topoisomerase Inhibitory Potential of Doxorubicin in Human Colon Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Anika Schroeter

    2014-12-01

    Full Text Available Resveratrol (RSV is currently being widely discussed as potentially useful for anticancer therapy in combination with classical chemotherapeutics, e.g., the topoisomerase II (TOP II poison doxorubicin (DOX. However, there is still a lack of knowledge of possible interference at the target enzyme, especially since RSV itself has recently been described to act as a TOP poison. We therefore sought to address the question whether RSV affects DOX-induced genotoxic and cytotoxic effects with special emphasis on TOP II in HT-29 colon carcinoma cells. RSV was found to counteract DOX-induced formation of DNA-TOP-intermediates at ≥100 µM for TOP IIα and at 250 µM for TOP IIβ. As a consequence, RSV modulated the DNA-strand breaking potential of DOX by mediating protective effects with an apparent maximum at 100 µM. At higher concentration ranges (≥200 µM RSV diminished the intracellular concentrations of DOX. Nevertheless, the presence of RSV slightly enhanced the cytotoxic effects of DOX after 1.5 h and 24 h of incubation. Taken together, at least in cell culture RSV was found to affect the TOP-poisoning potential of DOX and to modulate its cytotoxic effectiveness. Thus, further studies are needed to clarify the impact of RSV on the therapeutic effectiveness of DOX under in vivo conditions.

  19. The anticancer homeopathic composite "Canova Method" is not genotoxic for human lymphocytes in vitro.

    Science.gov (United States)

    Seligmann, Igor C; Lima, Patrícia D L; Cardoso, Plínio C S; Khayat, André S; Bahia, Marcelo O; Buchi, Dorli de Freitas; Cabral, Isabel R; Burbano, Rommel R

    2003-06-30

    The Canova Method (CM) is a homeopathic medicine indicated for the treatment of patients with cancer and for pathologies that involve a depressed immune system, such as AIDS. This product is composed of homeopathic dilutions of Aconitum napellus, Arsenicum album (arsenic trioxide), Bryonia alba, Lachesis muta venom and Thuya occidentalis. It stimulates the immune system by activating macrophages. Activated macrophages stimulate the lymphocytes so that they increase their cytotoxic action in response to tumoral growth or infection. Given that the CM stimulates and accelerates the activity of macrophages and lymphocytes, we evaluated genotoxic effects induced in human lymphocytes treated with this homeopathic medication in vitro. Structural and numerical chromosomal aberrations were scored for the assessment of induced genotoxic effects, while the variation in mitotic index was considered as a monitor for induced cellular toxicity. The lymphocytes were cultivated for 24, 48 or 72 h in the following final concentrations of the medicinal composite CM: 4, 8 and 12%. Treatments with the CM did not affect mitotic indexes, nor did they provoke chromosomal aberrations, when compared with untreated controls. There was no cytotoxicity or genotoxicity at the chromosomal level.

  20. Evaluation of the genotoxic potential of standardized extract of Glycyrrhiza glabra (GutGard™).

    Science.gov (United States)

    Chandrasekaran, C V; Sundarajan, K; Gupta, Anumita; Srikanth, H S; Edwin, Jothie; Agarwal, Amit

    2011-12-01

    Glycyrrhiza glabra Linn. (licorice) is widespread throughout the Mediterranean region and certain areas of Asia. Historically, the dried rhizome and root of the plant were used by the Chinese, Egyptian, Greek, Indian, and Roman civilizations as expectorant and carminative. In the modern medicinal system, licorice is used to treat liver ailments, dyspepsia, bronchitis, rheumatoid arthritis etc. Despite the extensive pharmacological applications, the genotoxic potential of G. glabra extract (GutGard™) has not been evaluated. Hence, this study was conducted to investigate the genotoxic potential of GutGard™ using battery of in vitro test systems: bacterial reverse mutation test (Ames II™), chromosome aberration (CA) and micronucleus (MN) tests. GutGard™ did not show significant increase in number of revertant colonies in Salmonella typhimurium strains (TA98 and TAMix) with/without S9 fraction. In CA and MN studies, GutGard™ did not show clastogenic effect at 4 and 18 h treatments with and without S9 fraction. Results indicated that GutGard™ is not mutagenic in a battery of genotoxicity tests.

  1. Chemical fate and genotoxic risk associated with hypochlorite treatment of nicotine

    Energy Technology Data Exchange (ETDEWEB)

    Zarrelli, Armando, E-mail: zarrelli@unina.it [UdR Napoli 4 Consorzio INCA, IC-REACH, Department of Organic Chemistry and Biochemistry, University Federico II, Naples (Italy); DellaGreca, Marina; Parolisi, Alice; Iesce, Maria Rosaria; Cermola, Flavio; Temussi, Fabio [UdR Napoli 4 Consorzio INCA, IC-REACH, Department of Organic Chemistry and Biochemistry, University Federico II, Naples (Italy); Isidori, Marina; Lavorgna, Margherita [Department of Life Sciences, II University of Naples, Caserta (Italy); Passananti, Monica; Previtera, Lucio [UdR Napoli 4 Consorzio INCA, IC-REACH, Department of Organic Chemistry and Biochemistry, University Federico II, Naples (Italy)

    2012-06-01

    Nicotine, the main alkaloid of tobacco, is a non- prescription drug to which all members of a tobacco-smoking society are exposed either through direct smoke inhalation or through second-hand passive 'smoking'. Nicotine is also commercially available in some pharmaceutical products and is used worldwide as a botanical insecticide in agriculture. Nicotine dynamics in indoor and outdoor environments as well as the human excretions and the manufacturing process are responsible for its entry in the environment through municipal and industrial wastewater discharges. The presence of nicotine in surface and ground waters points out that it survives a conventional treatment process and persists in potable-water supplies. Complete removal of nicotine is instead reported when additional chlorination steps are used. In this paper a simulation of STP chlorination of nicotine and a genotoxic evaluation of its main degradation products are reported. Under laboratory conditions removal of nicotine seems not to be due to mineralization but to transformation in oxidized and chlorinated products. The by-products have been isolated after fractionation by diverse chromatographic procedures and their structures determined using mass spectrometry and {sup 1}H and {sup 13}C NMR spectroscopy. Preliminary genotoxic SOS Chromotests with Escherichia coli PQ37 evidence no toxicity of the products. - Highlights: Black-Right-Pointing-Pointer Processes of chlorination in the treatment of raw water. Black-Right-Pointing-Pointer STP chlorination of nicotine. Black-Right-Pointing-Pointer Genotoxic evaluation of main degradation products of nicotine.

  2. 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.

  3. Assessment of genotoxic potential of two mycotoxins in the wing spot test of Drosophila melanogaster.

    Science.gov (United States)

    Gürbüzel, Mehmet; Uysal, Handan; Kızılet, Halit

    2015-03-01

    Mycotoxins, the toxic products of molds, exposure causes serious adverse health problems in human, animals, and crops. Determining the potential genotoxic effects of these substances is, therefore, of great importance. We have evaluated the genotoxic toxicity of two trichothecenes--diacetoxyscirpenol (DAS) and T-2 toxin--using the wing somatic mutation and recombination test (SMART) in Drosophila melanogaster. The SMART is based on the principle that the loss of heterozygosis of recessive markers located on the left arm of chromosome 3--multiple wing hairs (mwh) at the map position 0.3 and flare-3 (flr3) at the map position 38.8--may occur through various mechanisms such as mitotic recombination, mutation, deletion, half-translocation, chromosome loss, and nondisjunction. Both the mycotoxins were administered to third instar larvae (72 ± 4 h old) at concentrations ranging from 5 to 40 μM. Based on our results, DAS and T-2 toxins does not exert genotoxic effects up to a concentration of 40 μM.

  4. A review of the genotoxicity of 1,2-dichloroethane (EDC).

    Science.gov (United States)

    Gwinn, Maureen R; Johns, Douglas O; Bateson, Thomas F; Guyton, Kathryn Z

    2011-01-01

    1,2-Dichloroethane (EDC, CAS#107-06-2) is a high production volume halogenated aliphatic hydrocarbon that is used mainly in the manufacture of vinyl chloride. EDC has been found in ambient and residential air samples, as well as in groundwater, surface water and drinking water. EDC has been well-studied in a variety of genotoxicity assays, and appears to involve the metabolic activation of the parent compound. We critically evaluated the genotoxicity data of EDC and its metabolites as part of an evaluation of carcinogenic mechanisms of action of EDC. EDC is genotoxic in multiple test systems via multiple routes of exposure. EDC has been shown to induce DNA adduct formation, gene mutations and chromosomal aberrations in the presence of key activation enzymes (including CYP450s and/or GSTs) in laboratory animal and in vitro studies. EDC was negative for clastogenesis as measured by the micronucleus assay in mice. In general, an increased level of DNA damage is observed related to the GSH-dependent bioactivation of EDC. Increased chromosomal aberrations with increased CYP450 expression were suggestive of a role for the oxidative metabolites of EDC in inducing chromosomal damage. Taken together, these studies demonstrate that EDC exposure, in the presence of key enzymes (including CYP450s and/or GSTs), leads to DNA adduct formation, gene mutations and chromosomal aberrations.

  5. In vitro cytotoxic, genotoxic and antioxidant/oxidant effects of guaiazulene on human lymphocytes

    Directory of Open Access Journals (Sweden)

    Başak Toğar

    2015-02-01

    Full Text Available The aim of this study was to evaluate for the cytotoxicity, genotoxicity and antioxidant/oxidant activity of GYZ on human peripheral blood lymphocytes (PBLs. Guaiazulene (GYZ was added into culture tubes at various concentrations (0-400 µg/mL-1. Cytotoxicity against the human lymphocytes cultures was examined by lactate dehydrogenase (LDH release assay. The proliferative response was estimated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT assay. Antioxidant/oxidant activity was evaluated by measuring the total oxidant status (TOS and total antioxidant capacity (TAC levels. Micronucleus (MN and chromosomal aberration (CA tests were used in genotoxicity studies. The results showed that GYZ caused cytotoxicity in the PBLs at high concentrations, but TOS level were not affected, while the level of TAC was significantly increased. GYZ also did not induce chromosomal aberrations when compared to that of the control group. Results this study clearly revealed that GYZ was not genotoxic and also increased the capacity of the antioxidant in the culture of human PBL cells. This report is first report on the impact of GYZ on human PBL cells.

  6. Analysis of in vitro chemoprevention of genotoxic damage by phytochemicals, as single agents or as combinations.

    Science.gov (United States)

    Abraham, Suresh K; Eckhardt, Alexander; Oli, Rajaraman G; Stopper, Helga

    2012-05-15

    Cancer chemoprevention with low-dose combinations of bioactive phytochemicals instead of single agents has been suggested to induce less toxicity and improve efficacy. In this study, we selected four plant food-based phytochemicals, viz. chlorogenic acid (CLA), pelargonidin (PEL), resveratrol (RES) and epigallocatechin gallate (EGCG) to evaluate the in vitro chemoprevention of genotoxic damage in HL-60 cells. These agents were tested either individually or as a combination at two concentrations (with a 10-fold difference) against the genotoxins mitomycin C (MMC), diepoxybutane (DEB) and patulin (PAT). Our preliminary ferric reducing antioxidant power (FRAP) assay demonstrated additive effects when PEL, CLA, RES and EGCG were combined. Results of the cytokinesis-block micronucleus test showed significant protection against genotoxic damage induced by PAT, DEB and MMC when CLA, PEL, RES and EGCG were tested individually. This protective effect of the phytochemicals was not concentration-related. Both low- and high-concentration combinations of CLA, PEL, RES and EGCG showed significant reducing effects on the frequencies of micronuclei induced by PAT, DEB and MMC. However, the micronucleus test did not provide indications of additive or synergistic effects with this combination of phytochemicals. In conclusion, the chemo-preventive effects of PEL, CLA, RES and EGCG against genotoxic damage induced by MMC, DEB and PAT are indicative of a 'saturation effect' when higher concentrations and combinations of these phytochemicals are used.

  7. Evaluation of Hypoglycemic and Genotoxic Effect of Polyphenolic Bark Extract from Quercus sideroxyla

    Directory of Open Access Journals (Sweden)

    Marcela Soto-García

    2016-01-01

    Full Text Available Quercus sideroxyla is a wood species whose bark has phenolic compound and should be considered to be bioactive; the hypoglycemic and genotoxic properties of Q. sideroxyla bark were evaluated in this study. Total phenolic compound was determined in crude extract (CE and organic extract (OE. The OE has the highest amount of phenols (724.1±12.0 GAE/g. Besides, both CE and OE demonstrated effect over the inhibition of α-amylase in vitro. Hypoglycemic activity was assessed by glucose tolerance curve and the area under curve (UAC; OE showed the highest hypoglycemic activity. In addition, diabetes was induced by streptozotocin (65 mg/kg and the extracts (50 mg/kg were administered for 10 days; OE showed hypoglycemic effect compared with diabetic control and decreased hepatic lipid peroxidation. Acute toxicity and genotoxicity were evaluated in CE; results of acute toxicity did not show any mortality. Besides, the comet assay showed that CE at a dose of 100 mg/kg did not show any genotoxic effect when evaluated at 24 h, whereas it induced slight damage at 200 mg/kg, with the formation of type 1 comets.

  8. Quercetin protects human peripheral blood mononuclear cells from OTA-induced oxidative stress, genotoxicity, and inflammation.

    Science.gov (United States)

    Periasamy, Ramyaa; Kalal, Iravathy Goud; Krishnaswamy, Rajashree; Viswanadha, VijayaPadma

    2016-07-01

    Ochratoxin A (OTA) is one of the most abundant food-contaminating mycotoxins world wide, and is detrimental to human and animal health. This study evaluated the protective effect of quercetin against OTA-induced cytotoxicity, genotoxicity, and inflammatory response in lymphocytes. Cytotoxicity determined by MTT assay revealed IC20 value of OTA to be 20 µM, which was restored to near control values by pretreatment with quercetin. Oxidative stress parameters such as antioxidant enzymes, LPO and PCC levels indicated that quercetin exerted a protective effect on OTA-induced oxidative stress. Quercetin exerted an antigenotoxic effect on OTA-induced genotoxicity, by significantly reducing the number of structural aberrations in chromosomes and comet parameters like, % olive tail moment from 2.76 ± 0.02 to 0.56 ± 0.02 and % tail DNA from 56.23 ± 2.56 to 12.36 ± 0.56 as determined by comet assay. OTA-induced NO, TNF-α, IL-6, and IL-8 were significantly reduced in the quercetin pretreated samples indicating its anti-inflammatory role. Our results demonstrate for the first time that quercetin exerts a cytoprotective effect against OTA-induced oxidative stress, genotoxicity, and inflammation in lymphocytes. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 855-865, 2016.

  9. Evaluation of cytotoxicity and genotoxicity of Hancornia speciosa latex in Allium cepa root model.

    Science.gov (United States)

    Ribeiro, T P; Sousa, T R; Arruda, A S; Peixoto, N; Gonçalves, P J; Almeida, L M

    2016-02-01

    The latex obtained from Hancornia speciosa Gomes (Mangabeira tree) is widely used in traditional medicine to treat a variety of diseases, including diarrhea, ulcer, gastritis, tuberculosis, acne and warts. In this study, the cytotoxicity and genotoxicity effects of H. speciosa latex on the root meristem cells of Allium cepa were examined. Onion bulbs were exposed to different concentrations of latex and then submitted to microscopic analysis using Giemsa stain. Water was used as a negative control and sodium azide as a positive control. The results showed that, under the testing conditions, the mitotic index (MI) of the onion roots submitted to latex treatment did not differ significantly from the negative control, which suggests that the latex is not cytotoxic. Low incidence of chromosome aberrations in the cells treated with H. speciosa latex was also observed, indicating that the latex does not have genotoxic effect either. The MI and the chromosome aberration frequency responded to the latex concentration, requiring more studies to evaluate the dosage effect on genotoxicity. The results indicate that in tested concentrations H. speciosa latex is probably not harmful to human health and may be potentially used in medicine.

  10. 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.

  11. In vitro evaluation of genotoxic effects under magnetic resonant coupling wireless power transfer.

    Science.gov (United States)

    Mizuno, Kohei; Shinohara, Naoki; Miyakoshi, Junji

    2015-04-07

    Wireless power transfer (WPT) technology using the resonant coupling phenomenon has been widely studied, but there are very few studies concerning the possible relationship between WPT exposure and human health. In this study, we investigated whether exposure to magnetic resonant coupling WPT has genotoxic effects on WI38VA13 subcloned 2RA human fibroblast cells. WPT exposure was performed using a helical coil-based exposure system designed to transfer power with 85.4% efficiency at a 12.5-MHz resonant frequency. The magnetic field at the positions of the cell culture dishes is approximately twice the reference level for occupational exposure as stated in the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines. The specific absorption rate at the positions of the cell culture dishes matches the respective reference levels stated in the ICNIRP guidelines. For assessment of genotoxicity, we studied cell growth, cell cycle distribution, DNA strand breaks using the comet assay, micronucleus formation, and hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene mutation, and did not detect any significant effects between the WPT-exposed cells and control cells. Our results suggest that WPT exposure under the conditions of the ICNIRP guidelines does not cause detectable cellular genotoxicity.

  12. 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

  13. 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.

  14. Differential genotoxicity of diphenyl diselenide (PhSe2 and diphenyl ditelluride (PhTe2

    Directory of Open Access Journals (Sweden)

    Daiane Francine Meinerz

    2014-03-01

    Full Text Available Organoselenium compounds have been pointed out as therapeutic agents. In contrast, the potential therapeutic aspects of tellurides have not yet been demonstrated. The present study evaluated the comparative toxicological effects of diphenyl diselenide (PhSe2 and diphenyl ditelluride (PhTe2 in mice after in vivo administration. Genotoxicity (as determined by comet assay and mutagenicicity were used as end-points of toxicity. Subcutaneous administration of high doses of (PhSe2 or (PhTe2 (500 µmol/kg caused distinct genotoxicity in mice. (PhSe2 significantly decreased the DNA damage index after 48 and 96 h of its injection (p < 0.05. In contrast, (PhTe caused a significant increase in DNA damage (p < 0.05 after 48 and 96 h of intoxication. (PhSe2 did not cause mutagenicity but (PhTe2 increased the micronuclei frequency, indicating its mutagenic potential. The present study demonstrated that acute in vivo exposure to ditelluride caused genotoxicity in mice, which may be associated with pro-oxidant effects of diphenyl ditelluride. In addition, the use of this compound and possibly other related tellurides must be carefully controlled.

  15. Investigation of co-genotoxic effects of radiofrequency electromagnetic fields in vivo.

    Science.gov (United States)

    Verschaeve, L; Heikkinen, P; Verheyen, G; Van Gorp, U; Boonen, F; Vander Plaetse, F; Maes, A; Kumlin, T; Mäki-Paakkanen, J; Puranen, L; Juutilainen, J

    2006-05-01

    We investigated the possible combined genotoxic effects of radiofrequency (RF) electromagnetic fields (900 MHz, amplitude modulated at 217 Hz, mobile phone signal) with the drinking water mutagen and carcinogen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX). Female rats were exposed to RF fields for a period of 2 years for 2 h per day, 5 days per week at average whole-body specific absorption rates of 0.3 or 0.9 W/kg. MX was given in the drinking water at a concentration of 19 microg/ml. Blood samples were taken at 3, 6 and 24 months of exposure and brain and liver samples were taken at the end of the study (24 months). DNA damage was assessed in all samples using the alkaline comet assay, and micronuclei were determined in erythrocytes. We did not find significant genotoxic activity of MX in blood and liver cells. However, MX induced DNA damage in rat brain. Co-exposures to MX and RF radiation did not significantly increase the response of blood, liver and brain cells compared to MX exposure only. In conclusion, this 2-year animal study involving long-term exposures to RF radiation and MX did not provide any evidence for enhanced genotoxicity in rats exposed to RF radiation.

  16. Genotoxic potential evaluation of a cosmetic insoluble substance by the micronuclei assay.

    Science.gov (United States)

    Dayan, N; Shah, V; Minko, T

    2011-01-01

    An optical brightener (OB) powder (INCI: sodium silicoaluminate (and) glycidoxypropyl trimethyloxysilane/PEI-250 cross fluorescent brightener 230 salt (and) polyvinylalcohol crosspolymer) that is used in cosmetic facial products was tested for its genotoxic potential using the micronuclei test (MNT). It is a solid dry powder with an average size of 5 microns that is insoluble but dispersible in water. This study describes the exposure of cell culture to positive controls with and without enzymatic activation and to the test compound in different concentrations. We evaluated three end points: microscopic observation and quantification of micronuclei formation, and cell viability and proliferation. Both positive controls induced significant changes that were observed under the microscope and quantified. Based on its chemical nature, it was not anticipated that the test substance will degrade under the conditions of the experiments. However, the test is required to make sure that when solublized, impurities that may be present, even at trace levels, will not induce a genotoxic effect. The test compound did not promote micronuclei formation or change the viability or proliferation rate of cells. During this study we faced challenges such as solubilization and correlating viability data to genotoxicity data. These are described in the body of the paper. We believe that with the emergence of the 7(th) European amendment that bans animal testing, sharing these data and the study protocol serves as a key in building the understanding of the utilization of in vitro studies in the safety assessment of cosmetic ingredients.

  17. Genotoxic potential of the latex from cotton-leaf physicnut (Jatropha gossypiifolia L.

    Directory of Open Access Journals (Sweden)

    Pedro Marcos de Almeida

    2015-03-01

    Full Text Available Jatropha gossypiifolia L. (Euphorbiaceae, popularly known as cotton-leaf physicnut, is a milky shrub notable for its medicinal properties. The present study aimed to evaluate the toxic, cytotoxic and genotoxic effects of the latex of J. gossypiifolia, using Allium cepa L. as test system. Seeds of A. cepa were exposed to five concentrations of the latex (1.25; 2.5; 5; 10 and 20 mL/L in order to evaluate parameters of toxicity (evaluation of root growth, cytotoxicity (mitotic index frequency and genotoxicity (frequency of chromosome alterations. The latex showed a significant decrease in root mean growth value as well as mitotic index for the tested concentrations, except for 1.25 mL/L, when compared to results from the negative control. The 1.25, 2.5 and 5 mL/L concentrations induced significant chromo-some adherences, C-metaphases and/or chromosome bridges, as genotoxic effects. The significant frequency of chromosome bridges also indicated mutagenic potential for chromosomes of J. gossypiifolia as discussed in the paper. Considering that the latex is used in popular therapies, and that the test system A. cepa presents good correlation with tests carried out in mammals, it can be pointed out that its use for medicinal purposes may be harmful to human health especially if ingested.

  18. Acute genotoxicity analysis in vivo of the aqueous extract of Maytenus guyanensis Amazonian chichuá

    Directory of Open Access Journals (Sweden)

    Dionatas Ulises de Oliveira Meneguetti

    2015-04-01

    Full Text Available Abstract The species Maytenus guyanensis Klotzsch ex Reissek, Celastraceae, present a wide variety of possible pharmacological activities and its roots and stems are used by popular medicine in the western Amazon rainforest. Few studies have demonstrated the genotoxic safety of the popular use of this species, and owing to this, the present study aimed to perform an analysis of the acute genotoxicity in vivo of the aqueous extract of M. guyanensis. Male and female mice from Mus musculus species, of weights ranging from 20 to 40 g, organized in eight groups with different treatments were used. The aqueous extracts of the bark of M. guyanensis were administered orally by gavage with 0.1 ml of the test substance per 10 g of the animal, followed by performance of comet assay in peripheral blood, PCE/NCE correlation and occurrence of micronuclei in the bone marrow. It was found that the aqueous extract of M. guyanensis, with ten times higher concentration than those used in ethnopharmacology, did not present genotoxic effect and, moreover, it has antigenotoxic action in mice treated acutely. Further studies regarding bioaccumulation and chronic effects of this species are suggested, in order to improve the understanding of its mechanism of action, ensuring the efficacy and safety of its utilization and developing phytotherapics and drugs.

  19. The Cosmetics Europe strategy for animal-free genotoxicity testing: project status up-date.

    Science.gov (United States)

    Pfuhler, S; Fautz, R; Ouedraogo, G; Latil, A; Kenny, J; Moore, C; Diembeck, W; Hewitt, N J; Reisinger, K; Barroso, J

    2014-02-01

    The Cosmetics Europe (formerly COLIPA) Genotoxicity Task Force has driven and funded three projects to help address the high rate of misleading positives in in vitro genotoxicity tests: The completed "False Positives" project optimized current mammalian cell assays and showed that the predictive capacity of the in vitro micronucleus assay was improved dramatically by selecting more relevant cells and more sensitive toxicity measures. The on-going "3D skin model" project has been developed and is now validating the use of human reconstructed skin (RS) models in combination with the micronucleus (MN) and Comet assays. These models better reflect the in use conditions of dermally applied products, such as cosmetics. Both assays have demonstrated good inter- and intra-laboratory reproducibility and are entering validation stages. The completed "Metabolism" project investigated enzyme capacities of human skin and RS models. The RS models were shown to have comparable metabolic capacity to native human skin, confirming their usefulness for testing of compounds with dermal exposure. The program has already helped to improve the initial test battery predictivity and the RS projects have provided sound support for their use as a follow-up test in the assessment of the genotoxic hazard of cosmetic ingredients in the absence of in vivo data.

  20. 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.

  1. Embryotoxicity and genotoxicity evaluation of sediments from Yangtze River estuary using zebrafish (Danio rerio) embryos.

    Science.gov (United States)

    Li, Qian; Chen, Ling; Liu, Li; Wu, Lingling

    2016-03-01

    Sediments function both as a sink and a source of pollutants in aquatic ecosystems and may impose serious effects on benthic organisms and human health. As one of the largest estuaries in the world, the Yangtze River estuary suffers from abundant wastewater from the coastal cities. In this study, the zebrafish (Danio rerio) embryos were employed in the fish embryo test and a comet assay to evaluate the embryotoxicity and genotoxicity of the sediments from the Yangtze River estuary, respectively. Results showed that the sediments from the Yangtze River estuary significantly increased mortality, induced development abnormalities, and reduced hatching rate and heart rate of zebrafish embryos after 96 h of exposure. Significant genotoxicity was observed in the samples relative to the controls. Relatively low-level embryotoxicity and genotoxicity of sediments were found in the Yangtze River compared with other river systems. Toxic responses were also discussed in relation to the analyzed organic contaminants in sediments. More attention should be paid to non-priority pollutant monitoring in the Yangtze River estuary.

  2. Oxidative and genotoxic effects of 900 MHz electromagnetic fields in the earthworm Eisenia fetida.

    Science.gov (United States)

    Tkalec, Mirta; Stambuk, Anamaria; Srut, Maja; Malarić, Krešimir; Klobučar, Göran I V

    2013-04-01

    Accumulating evidence suggests that exposure to radiofrequency electromagnetic field (RF-EMF) can have various biological effects. In this study the oxidative and genotoxic effects were investigated in earthworms Eisenia fetida exposed in vivo to RF-EMF at the mobile phone frequency (900 MHz). Earthworms were exposed to the homogeneous RF-EMF at field levels of 10, 23, 41 and 120 V m(-1) for a period of 2h using a Gigahertz Transversal Electromagnetic (GTEM) cell. At the field level of 23 V m(-1) the effect of longer exposure (4h) and field modulation (80% AM 1 kHz sinusoidal) was investigated as well. All exposure treatments induced significant genotoxic effect in earthworms coelomocytes detected by the Comet assay, demonstrating DNA damaging capacity of 900 MHz electromagnetic radiation. Field modulation additionally increased the genotoxic effect. Moreover, our results indicated the induction of antioxidant stress response in terms of enhanced catalase and glutathione reductase activity as a result of the RF-EMF exposure, and demonstrated the generation of lipid and protein oxidative damage. Antioxidant responses and the potential of RF-EMF to induce damage to lipids, proteins and DNA differed depending on the field level applied, modulation of the field and duration of E. fetida exposure to 900 MHz electromagnetic radiation. Nature of detected DNA lesions and oxidative stress as the mechanism of action for the induction of DNA damage are discussed.

  3. Tradescantia micronucleus test indicates genotoxic potential of traffic emissions in European cities

    Energy Technology Data Exchange (ETDEWEB)

    Klumpp, Andreas [Institute for Landscape and Plant Ecology (320), University of Hohenheim, 70593 Stuttgart (Germany)]. E-mail: aklumpp@uni-hohenheim.de; Ansel, Wolfgang [Institute for Landscape and Plant Ecology (320), University of Hohenheim, 70593 Stuttgart (Germany); Klumpp, Gabriele [Institute for Landscape and Plant Ecology (320), University of Hohenheim, 70593 Stuttgart (Germany); Calatayud, Vicent [Fundacion CEAM, Parque Tecnologico, c/Charles Darwin 14, 46980 Paterna, Valencia (Spain); Garrec, Jean Pierre [INRA Nancy, Laboratoire Pollution Atmospherique, 54280 Champenoux (France); He Shang [INRA Nancy, Laboratoire Pollution Atmospherique, 54280 Champenoux (France); Penuelas, Josep [Unitat Ecofisiologia CSIC-CEAB-CREAF, Universitat Autonoma de Barcelona, Ed. C, 08193 Bellaterra, Barcelona (Spain); Ribas, Angela [Unitat Ecofisiologia CSIC-CEAB-CREAF, Universitat Autonoma de Barcelona, Ed. C, 08193 Bellaterra, Barcelona (Spain); Ro-Poulsen, Helge [Botanical Institute, University of Copenhagen, Oster Farimagsgade 2D, 1353 Copenhagen K (Denmark); Rasmussen, Stine [Botanical Institute, University of Copenhagen, Oster Farimagsgade 2D, 1353 Copenhagen K (Denmark); Sanz, Maria Jose [Fundacion CEAM, Parque Tecnologico, c/Charles Darwin 14, 46980 Paterna, Valencia (Spain); Vergne, Phillippe [ENS Lyon and Lyon Botanical Garden, 46 Allee d' Italie, 69364 Lyon Cedex 07 (France)

    2006-02-15

    Urban atmospheres contain complex mixtures of air pollutants including mutagenic and carcinogenic substances such as benzene, diesel soot, heavy metals and polycyclic aromatic hydrocarbons. In the frame of a European network for the assessment of air quality by the use of bioindicator plants, the Tradescantia micronucleus (Trad-MCN) test was applied to examine the genotoxicity of urban air pollution. Cuttings of Tradescantia clone no. 4430 were exposed to ambient air at 65 monitoring sites in 10 conurbations employing a standardised methodology. The tests revealed an elevated genotoxic potential mainly at those urban sites which were exposed to severe car traffic emissions. This bioassay proved to be a suitable tool to detect local 'hot spots' of mutagenic air pollution in urban areas. For its use in routine monitoring programmes, however, further standardisation of cultivation and exposure techniques is recommended in order to reduce the variability of results due to varying environmental conditions. - The Tradescantia micronucleus test can be used to assess genotoxic potential at urban sites.

  4. 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.

  5. Mutagenic and genotoxic activity of chosen dyes and surface active compounds used in the textile industry.

    Science.gov (United States)

    Przybojewska, B; Barański, B; Spiechowicz, E; Szymczak, W

    1989-01-01

    This study was designed to investigate the mutagenic and genotoxic properties of ten dyes and four surface active compounds using Salmonella/microsome assay and the micronucleus test. Five of the investigated dyes (Acid Blue 7, Acid Green 16, Direct Black 19:1, Basic Red 22, Basic Orange 28) possessed mutagenic activity with regard to test strains of Salmonella. In addition, all of them increased the frequency of micronucleated polychromatic erythrocytes in the bone marrow of mice. Three other compounds (Acid Blue 62, Direct Yellow 12, Direct Red 81), which were not mutagenic in the Salmonella/microsome assay, were genotoxic in the micronucleus test. The other two dyes (Reactive Blue 13, Acid Red 213), as well as tested surface active compounds, did not exert mutagenic and genotoxic effects, and therefore, it is most probable that they do not have carcinogenic properties. Besides, it was noted that Acid Blue 62, Direct Black 19:1, Direct Red 81 and Basic Orange 28 cause a significant decrease in the ratio polychromatic to normochromatic erythrocytes in the bone marrow of mice, which means that, at the doses used in the experiment, they are toxic to the erythrocyte series cells of bone marrow. The other compounds under consideration have no such effect.

  6. Genotoxic potential of TiO2 on bottlenose dolphin leukocytes.

    Science.gov (United States)

    Bernardeschi, Margherita; Guidi, Patrizia; Scarcelli, Vittoria; Frenzilli, Giada; Nigro, Marco

    2010-01-01

    Titanium dioxide is extensively used in a variety of products, including industrial materials and cosmetics. Studies mainly performed on human cell lines and in vivo exposure on experimental animals have raised concern about the toxic effects of ultrafine titanium dioxide; however, scarce information is available about its impact on aquatic life. The aim of this article was to assess the genotoxic potential of TiO(2) (anatase and rutile) on bottlenose dolphin leukocytes. Blood samples were obtained from four male and one female specimens reared at the Adriatic SeaWorld "Oltremare" (Riccione, Italy). Leukocytes were isolated by the lyses procedure and in vitro exposed to TiO(2) in RPMI. Experimental solutions were sonicated immediately before dosing the cells. Three exposure times (4, 24 and 48 h) and three doses (20, 50 and 100 microg/ml) were tested. Genotoxicity was detected by the single-cell gel electrophoresis (or comet assay) at pH > or = 13, assessing single/double-strand breaks and alkali-labile sites. Cytotoxicity was also detected by the Trypan blue exclusion method. Results showed that both the crystalline forms of TiO(2) were genotoxic for bottlenose dolphin leukocytes, with a statistically significant increase of DNA fragmentation after exposure to 50 and 100 microg/ml for 24 and 48 h. Although preliminary, these are the first data regarding the genetic susceptibility of toothed cetaceans toward an "emerging" pollutant, such as TiO(2) particles.

  7. Genotoxic Effects of Superconducting Static Magnetic Fields (SMFs) on Wheat (Triticum aestivum) Pollen Mother Cells (PMCs)

    Science.gov (United States)

    Zhang, Pingping; Yin, Ruochun; Chen, Zhiyou; Wu, Lifang; Yu, Zengliang

    2007-04-01

    The effects of superconducting static magnetic fields (SMFs) on the pollen mother cells (PMCs) of wheat were investigated in order to evaluate the possible genotoxic effect of such non-ionizing radiation. The seeds of wheat were exposed to static magnetic fields with either different magnetic flux densities (0, 1, 3, 5 and 7 Tesla) for 5 h or different durations (1, 3 and 5 h) at a magnetic flux density of 7 Tesla. The seeds were germinated at 23oC after exposure and the seedlings were transplanted into the field. The PMCs from young wheat ears were taken and slides were made following the conventional method. The genotoxic effect was evaluated in terms of micronucleus (MN), chromosomal bridge, lagging chromosome and fragments in PMCs. Although the exposed groups of a low field intensity (below 5 Tesla) showed no statistically significant difference in the aberration frequency compared with the unexposed control groups and sham exposed groups, a significant increase in the chromosomal bridge, lagging chromosome, triple-polar segregation or micronucleus was observed at a field strength of 5 Tesla or 7 Tesla, respectively. The analysis of dose-effect relationships indicated that the increased frequency of meiotic abnormal cells correlated with the flux density of the magnetic field and duration, but no linear relationship was observed. Such statistically significant differences indicated a potential genotoxic effect of high static magnetic fields above 5 T.

  8. 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

  9. Cytogenetic genotoxic investigation in peripheral blood lymphocytes of subjects with dental composite restorative filling materials.

    Science.gov (United States)

    Pettini, F; Savino, M; Corsalini, M; Cantore, S; Ballini, A

    2015-01-01

    Dental composite resins are biomaterials commonly used to aesthetically restore the structure and function of teeth impaired by caries, erosion, or fracture. Residual monomers released from resin restorations as a result of incomplete polymerization processes interact with living oral tissues. The objective of this study was to evaluate the genotoxicity of a common dental composite material (Enamel Plus-HFO), in subjects with average 13 filled teeth with the same material, compared to a control group (subjects having neither amalgam nor composite resin fillings). Genotoxicity assessment of composite materials was carried out in vitro in human peripheral blood leukocytes using sister-chromatid exchange (SCE) and chromosomal aberrations (CA) cytogenetic tests. The results of correlation and multiple regression analyses confirmed the absence of a relationship between SCE/cell, high frequency of SCE(HFC) or CA frequencies and exposure to dental composite materials. These results indicate that composite resins used for dental restorations differ extensively in vivo in their cytotoxic and genotoxic potential and in their ability to affect chromosomal integrity, cell-cycle progression, DNA replication and repair.

  10. Carboxylated nanodiamonds are neither cytotoxic nor genotoxic on liver, kidney, intestine and lung human cell lines.

    Science.gov (United States)

    Paget, V; Sergent, J A; Grall, R; Altmeyer-Morel, S; Girard, H A; Petit, T; Gesset, C; Mermoux, M; Bergonzo, P; Arnault, J C; Chevillard, S

    2014-08-01

    Although nanodiamonds (NDs) appear as one of the most promising nanocarbon materials available so far for biomedical applications, their risk for human health remains unknown. Our work was aimed at defining the cytotoxicity and genotoxicity of two sets of commercial carboxylated NDs with diameters below 20 and 100 nm, on six human cell lines chosen as representative of potential target organs: HepG2 and Hep3B (liver), Caki-1 and Hek-293 (kidney), HT29 (intestine) and A549 (lung). Cytotoxicity of NDs was assessed by measuring cell impedance (xCELLigence® system) and cell survival/death by flow cytometry while genotoxicity was assessed by γ-H2Ax foci detection, which is considered the most sensitive technique for studying DNA double-strand breaks. To validate and check the sensitivity of the techniques, aminated polystyrene nanobeads were used as positive control in all assays. Cell incorporation of NDs was also studied by flow cytometry and luminescent N-V center photoluminescence (confirmed by Raman microscopy), to ensure that nanoparticles entered the cells. Overall, we show that NDs effectively entered the cells but NDs do not induce any significant cytotoxic or genotoxic effects on the six cell lines up to an exposure dose of 250 µg/mL. Taken together these results strongly support the huge potential of NDs for human nanomedicine but also their potential as negative control in nanotoxicology studies.

  11. Genotoxicity assessment of pesticides on terrestrial snail embryos by analysis of random amplified polymorphic DNA profiles.

    Science.gov (United States)

    Baurand, Pierre-Emmanuel; Capelli, Nicolas; de Vaufleury, Annette

    2015-11-15

    The study explores the relevance of coupling Random Amplified Polymorphic DNA (RAPD) and a High-Resolution capillary electrophoresis System (HRS) method for assessing the genotoxic potential of the wide variety commercial formulations of pesticides. Using this technique, the genotoxic potential of a glyphosate-based herbicide (Roundup Flash(®) (RU)) and two fungicide formulations based on tebuconazole and copper (Corail(®) and Bordeaux mixture (BM), respectively) was evaluated on terrestrial snail embryos. Clutches of Cantareus aspersus were exposed during their entire embryonic development to a range of concentration around the EC50 values (based on hatching success) for each compound tested. Three primers were used for the RAPD amplifications of pesticides samples. RAPD-HRS revealed concentration-dependent modifications in profiles generated with the three primers in RU(®)-exposed embryos from 30 mg/L glyphosate. For Corail(®)-exposed embryos, only two of the three primers were able to show alterations in profiles from 0.05 mg/L tebuconazole. For BM-exposed embryos, no signs of genotoxicity were observed. All changes observed in amplification profiles have been detected at concentrations lower than the recommended doses for vineyard field applications. Our study demonstrates the efficiency of coupling RAPD and HRS to efficiently screen the effect of pesticide formulations on DNA.

  12. 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.

  13. 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.

  14. Evaluation of the Genotoxicity of Bangpungtongsung-San, a Traditional Herbal Prescription

    Directory of Open Access Journals (Sweden)

    In-Sik Shin

    2014-01-01

    Full Text Available Bangpungtongsung-san (BPS is a traditional Korean herbal formula used as an anti-inflammatory, antipyretic, antiobesity, and choleretic agent, which consists of 18 herbs. As part of a safety evaluation of BPS, the present study evaluated the potential genotoxicity of an aqueous BPS extract using a standard battery of tests, including, the Ames test, chromosomal aberration test, and mouse micronucleus test. The BPS extract was not found to be genotoxic under the conditions of the Ames test. In micronucleus test, oral administration of BPS at doses up to 2,000 mg/kg did not increases the incidence of micronucleated polychromatic erythrocyte. The chromosomal aberration test showed that the BPS extract induced an increase in the number of structural and numerical chromosomal aberrations in the group treated with BPS at high dose levels (2,500 and 4,000 μg/mL for 6 h, in the presence of the metabolic activation system (S-9 mix, compared with the vehicle control. In conclusion, these results indicate that BPS extract may act as a genotoxic agent.

  15. Genotoxic evaluation of Halfenprox using the human peripheral lymphocyte micronucleus assay and the Ames test.

    Science.gov (United States)

    Akyıl, Dilek; Eren, Yasin; Konuk, Muhsin; Dere, Hatice; Serteser, Ahmet

    2017-04-01

    The genotoxicity and mutagenicity of Halfenprox, a synthetic pyrethroid insecticide and acaricide, was assessed using two standard genotoxicity assays of the Salmonella typhimurium mutagenicity assay (Ames test) and in vitro micronucleus (MN) assay in human peripheral lymphocytes. In the Ames test, Salmonella strains TA98 and TA100 were treated with or without S9 fraction. The doses of Halfenprox were 6.25, 12.5, 25, 50, and 100 μg/plate and test materials were dissolved in DMSO. The concentrations of Halfenprox did not show mutagenic activity on both strains with and without S9 fraction. The MN assay was used to investigate the genotoxic effects of Halfenprox in human peripheral lymphocytes treated with 250, 500, 750, and 1000 μg/ml concentrations of Halfenprox for 24 and 48 h, and at 1000 μg/ml the concentration was significantly increased and the MN formation was compared with the negative control for both treatment periods. In addition, a significant decrease of the nuclear devision index (NDI) values at the higher concentrations of Halfenprox and at both treatment periods was observed.

  16. ROS-mediated genotoxicity of asbestos-cement in mammalian lung cells in vitro

    Directory of Open Access Journals (Sweden)

    Rödelsperger Klaus

    2005-10-01

    Full Text Available Abstract Asbestos is a known carcinogen and co-carcinogen. It is a persisting risk in our daily life due to its use in building material as asbestos-cement powder. The present study done on V79-cells (Chinese hamster lung cells demonstrates the cytotoxic and genotoxic potential of asbestos-cement powder (ACP in comparison with chrysotile asbestos. A co-exposure of chrysotile and ACP was tested using the cell viability test and the micronucleus assay. The kinetochore analysis had been used to analyse the pathway causing such genotoxic effects. Thiobarbituric acid-reactive substances were determined as evidence for the production of reactive oxygen species. Both, asbestos cement as well as chrysotile formed micronuclei and induced loss of cell viability in a concentration- and time- dependent way. Results of TBARS analysis and iron chelator experiments showed induction of free radicals in ACP- and chrysotile exposed cultures. CaSO4 appeared to be a negligible entity in enhancing the toxic potential of ACP. The co-exposure of both, ACP and chrysotile, showed an additive effect in enhancing the toxicity. The overall study suggests that asbestos-cement is cytotoxic as well as genotoxic in vitro. In comparison to chrysotile the magnitude of the toxicity was less, but co-exposure increased the toxicity of both.

  17. The Combined Toxic and Genotoxic Effects of Cd and As to Plant Bioindicator Trifolium repens L

    Science.gov (United States)

    Ghiani, Alessandra; Fumagalli, Pietro; Nguyen Van, Tho; Gentili, Rodolfo; Citterio, Sandra

    2014-01-01

    This study was undertaken to investigate combined toxic and genotoxic effects of cadmium (Cd) and arsenic (As) on white clover, a pollutant sensitive plant frequently used as environmental bioindicator. Plants were exposed to soil spiked with increasing concentrations of cadmium sulfate (20, 40 and 60 mg Kg−1) or sodium arsenite (5, 10 and 20 mg Kg−1) as well as with their combinations. Metal(loid) bioavailability was assessed after soil contamination, whereas plant growth, metal(loid) concentration in plant organs and DNA damage were measured at the end of plant exposition. Results showed that individual and joint toxicity and genotoxicity were related to the concentration of Cd and As measured in plant organs, and that As concentration was the most relevant variable. Joint effects on plant growth were additive or synergistic, whereas joint genotoxic effects were additive or antagonistic. The interaction between Cd and As occurred at both soil and plant level. In soil the presence of As limited the bioavailability of Cd, whereas the presence of Cd increased the bioavailability of As. Nevertheless only As biovailability determined the amount of As absorbed by plants. The amount of Cd absorbed by plant was not linearly correlated with the fraction of bioavailable Cd in soil suggesting the involvement of additional factors, such as plant uptake mechanisms. These results reveal that the simultaneous presence in soil of Cd and As, although producing an additive or synergistic toxic effect on Trifolium repens L. growth, generates a lower DNA damage. PMID:24914541

  18. Influence Of Acacia nilotica On Arsenic Induced Genotoxicity In Male and Female Mice

    Directory of Open Access Journals (Sweden)

    INAS S. Ghaly AND ZEINAB E. HANAFY

    2010-06-01

    Full Text Available For centuries, plants have been used in traditional medicine and there has been recent interest in the chemopreventive properties of compounds derived from plants. In the present study, we investigated the effects of extracts of Acacia nilotica leaves on the genotoxicity of arsinic . Arsenic contamination in groundwater a global human health hazard .There is no effective remedial action of chronic arsenicsis. However, a well-nourished diet can modulate the onset of adverse health effects and delayed the effect of arsenic in drinking water. In the present work, genotoxic effects were induced by sodium arsenate through oral administration,and the protective effect of Acacia nilotica was studied. Chromosomal aberrations were more pronounced in sodium arsenate treated mice, while supplementation of Acacia nilotica with sodium arsenate reduced the incidence of the aberrations. The mean of DNA fragmentation induced by sodium arsenate was highly significant increase. However, the administration of Acacia nilotica significantly decreased DNA fragmentation induced by sodium arsenate. The mean number of sperms, were decreased significantly after treatment with sodium arsenate, while administration of Acacia nilotica increased the number of sperm in mice treated with sodium arsenate, and also decreased the percentage of sperm abnormalities induced by sodium arsenate. The outcome of study showed that Acacia nilotica has the efficiency to encounter the genotoxic effects induced by arsenic.

  19. Genotoxicity of Microcystin-LR in In Vitro and In Vivo Experimental Models

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    Elsa Dias

    2014-01-01

    Full Text Available Microcystin-LR (MCLR is a cyanobacterial toxin known for its acute hepatotoxicity. Despite being recognized as tumour promoter, its genotoxicity is far from being completely clarified, particularly in organs other than liver. In this work, we used the comet and/or the micronucleus (MN assays to study the genotoxicity of MCLR in kidney- (Vero-E6 and liver-derived (HepG2 cell lines and in blood cells from MCLR-exposed mice. MCLR treatment (5 and 20 μM caused a significant induction in the MN frequency in both cell lines and, interestingly, a similar positive effect was observed in mouse reticulocytes (37.5 μg MCLR/kg, i.p. route. Moreover, the FISH-based analysis of the MN content (HepG2 cells suggested that MCLR induces both chromosome breaks and loss. On the other hand, the comet assay results were negative in Vero-E6 cells and in mouse leukocytes, with the exception of a transient increase in the level of DNA damage 30 minutes after mice exposure. Overall, the present findings contributed to increase the weight of evidence in favour of MCLR genotoxicity, based on its capacity to induce permanent genetic damage either in vitro or in vivo. Moreover, they suggest a clastogenic and aneugenic mode of action that might underlie a carcinogenic effect.

  20. Sensitivity of Bidens laevis L. to mutagenic compounds. Use of chromosomal aberrations as biomarkers of genotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Perez, D.J. [Laboratorio de Genetica, Estacion Experimental Agropecuaria Balcarce (INTA), Facultad de Ciencias Agrarias, UNMdP, CC 276, 7620 Balcarce (Argentina); Laboratorio de Ecotoxicologia, Departamento de Ciencias Marinas, Facultad de Ciencias Exactas y Naturales, UNMdP, Funes 3350, 7600 Mar del Plata (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Rivadavia 1917, 1033 Buenos Aires (Argentina); Lukaszewicz, G. [Laboratorio de Ecotoxicologia, Departamento de Ciencias Marinas, Facultad de Ciencias Exactas y Naturales, UNMdP, Funes 3350, 7600 Mar del Plata (Argentina); Menone, M.L., E-mail: lujanm@mdp.edu.a [Laboratorio de Ecotoxicologia, Departamento de Ciencias Marinas, Facultad de Ciencias Exactas y Naturales, UNMdP, Funes 3350, 7600 Mar del Plata (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Rivadavia 1917, 1033 Buenos Aires (Argentina); Camadro, E.L. [Laboratorio de Genetica, Estacion Experimental Agropecuaria Balcarce (INTA), Facultad de Ciencias Agrarias, UNMdP, CC 276, 7620 Balcarce (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Rivadavia 1917, 1033 Buenos Aires (Argentina)

    2011-01-15

    The wetland macrophyte Bidens laevis possesses suitable cytological characteristics for genotoxicity testing. To test its sensitivity as compared to terrestrial plants species currently in use in standardized assays, Methyl Methanesulfonate (MMS), N-ethyl-N-nitrosourea (ENU) and Maleic Hydrazide (HM) were used. On the other hand, the insecticide Endosulfan (ES) - an environmentally relevant contaminant - was assayed in seeds and two-month old plants. Mitotic Index (MI), frequency of Chromosome Aberrations in Anaphase-Telophase (CAAT) and frequency of Abnormal Metaphases (AM) were analyzed. MH, MMS and ENU caused a significant decrease of the MI. MMS was aneugenic whereas MH and ENU were both aneugenic and clastogenic. ES caused a significant concentration-dependent increase of total- and aneugenic-CAAT in roots and a significant high frequency of AM at high concentrations. Because of its sensitivity to mutagenic substances, B. laevis can be regarded as a reliable and convenient species for genotoxicity assays especially if aquatic contaminants are evaluated. - The wetland macrophyte Bidens laevis is sensitive to genotoxic compounds similarly to terrestrial standardized species.

  1. 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......μgmL(-1); or under dark conditions at concentrations up to 667μgmL(-1), though cytotoxicity was seen at the higher concentrations. Additionally, the growth factor calculation was influenced by a shading effect due to ENPs, and was corrected by considering the pre-incubation OD readings of Plate B...

  2. 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.

  3. Genotoxicity and mutagenicity of Echinodorus macrophyllus (chapéu-de-couro extracts

    Directory of Open Access Journals (Sweden)

    Leonardo S. Vidal

    2010-01-01

    Full Text Available Echinodorus macrophyllus, commonly known as chapéu-de-couro, is a medicinal plant used in folk medicine to treat inflammation and rheumatic diseases. In this work, we used short-term bacterial assays based on the induction of SOS functions to examine the genotoxicity and mutagenicity of an aqueous extract of E. macrophyllus leaves. Whole extract and an ethyl acetate fraction showed similar genotoxicity and caused an ~70-fold increase in lysogenic induction. The extract also gave a positive result in the SOS chromotest with an increase of 12-fold in β-Galactosidase enzymatic units. There was a strong trend towards base substitutions and frameshifts at purine sites in the mutations induced by the extract in Escherichia coli (CC103 and CC104 strains and Salmonella typhimurium test strains (22-fold increase in histidine revertants in TA98 strain. Since reactive oxygen species may be implicated in aging process and in degenerative diseases, we used antioxidant compounds as catalase, thiourea and dipyridyl in the lysogenic induction test. All this compounds were able to reduce the induction factor observed in the treatment with chapéu-de-couro, thus suggesting that the genotoxicity and mutagenicity were attributable to the production of reactive oxygen species that targeted DNA purines.

  4. 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.

  5. Identification and characterization of enhancer-blocking insulators to reduce retroviral vector genotoxicity.

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    Amy C Groth

    Full Text Available The chromatin insulator cHS4 can reduce silencing chromosomal position effects and genotoxicity associated with integrating viral vectors. However, the fully active version of this element can also reduce vector titers and is only partially effective. In order to identify alternatives to cHS4, we developed a functional lentiviral vector-based reporter screen for enhancer-blocking insulators. Using this system, we screened candidate sequences that were initially identified by chromatin profiling for binding by CTCF and for DNase hypersensitivity. All 12 analyzed candidates blocked enhancer-promoter activity. The enhancer-blocking activity of the top two candidates was confirmed in two complementary plasmid-based assays. Studies in a gammaretroviral reporter vector indicated these two candidates have little to no effect on vector titers, and do not diminish vector expression in primary mouse bone marrow cultures. Subsequent assessment in a mouse in vivo tumor formation model demonstrated that both candidates reduced the rate of gammaretroviral vector-mediated genotoxicity as effectively as the cHS4 insulator. In summary, we have developed a novel lentiviral vector-based method of screening candidate elements for insulator activity, and have used this method to identify two new insulator elements capable of improving the safety of retroviral vectors without diminishing vector titers or expression. These findings expand the limited arsenal of insulators functionally validated to reduce the rate of retroviral vector-mediated genotoxicity.

  6. Bacterial Composition, Genotoxicity, and Cytotoxicity of Fecal Samples from Individuals Consuming Omnivorous or Vegetarian Diets

    Science.gov (United States)

    Federici, Ermanno; Prete, Roberta; Lazzi, Camilla; Pellegrini, Nicoletta; Moretti, Massimo; Corsetti, Aldo; Cenci, Giovanni

    2017-01-01

    This study analyzes the composition of viable fecal bacteria and gut toxicology biomarkers of 29 healthy volunteers, who followed omnivorous, lacto-ovo-vegetarian, or vegan diets. In particular, the research was focused on the prevalence of some representative viable bacteria from the four dominant phyla (Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria) commonly present in human feces, in order to evaluate the relationship between microorganisms selected by the habitual dietary patterns and the potential risk due to fecal water (FW) genotoxicity and cytotoxicity, considered as biomarkers for cancer risk and protective food activity. The relative differences of viable bacteria among dietary groups were generally not statistically significant. However, compared to omnivores, lacto-ovo-vegetarians showed low levels of total anaerobes. Otherwise, vegans showed total anaerobes counts similar to those of omnivores, but with lower number of bifidobacteria and the highest levels of bacteria from the Bacteroides–Prevotella genera. FW genotoxicity of lacto-ovo-vegetarians resulted significantly lower either in relation to that of omnivores and vegans. Lacto-ovo-vegetarians also showed the lowest levels of cytotoxicity, while the highest were found for vegans. These results highlighted that lacto-ovo-vegetarian diet was particularly effective in a favorable modulation of microbial activity, thus contributing to a significant reduction of the genotoxic and cytotoxic risk in the gut. PMID:28293225

  7. Genotoxic effects of eugenol, isoeugenol and safrole in the wing spot test of Drosophila melanogaster.

    Science.gov (United States)

    Munerato, Maria Cristina; Sinigaglia, Marialva; Reguly, Maria Luíza; de Andrade, Heloísa Helena Rodrigues

    2005-04-01

    In the present study, the phenolic compounds eugenol, isoeugenol and safrole were investigated for genotoxicity in the wing spot test of Drosophila melanogaster. The Drosophila wing somatic mutation and recombination test (SMART) provides a rapid means to evaluate agents able to induce gene mutations and chromosome aberrations, as well as rearrangements related to mitotic recombination. We applied the SMART in its standard version with normal bioactivation and in its variant with increased cytochrome P450-dependent biotransformation capacity. Eugenol and safrole produced a positive recombinagenic response only in the improved assay, which was related to a high CYP450-dependent activation capacity. This suggests, as previously reported, the involvement of this family of enzymes in the activation of eugenol and safrole rather than in its detoxification. On the contrary, isoeugenol was clearly non-genotoxic at the same millimolar concentrations as used for eugenol in both the crosses. The responsiveness of SMART assays to recombinagenic compounds, as well as the reactive metabolites from eugenol and safrole were considered responsible for the genotoxicity observed.

  8. Protein serine/threonine phosphatase PPEF-1 suppresses genotoxic stress response via dephosphorylation of PDCD5

    Science.gov (United States)

    Park, Soo-Yeon; Seo, Jaesung; Choi, Hyo-Kyoung; Oh, Hye-Jeong; Guk, Garam; Lee, Yoo-Hyun; Lee, Jeongmin; Jun, Woo Jin; Choi, Kyung-Chul; Yoon, Ho-Geun

    2017-01-01

    Programmed cell death 5 (PDCD5) is believed to play a crucial role in p53 activation; however, the underlying mechanism of how PDCD5 function is regulated during apoptosis remains obscure. Here, we report that the serine/threonine phosphatase PPEF-1 interacts with and dephosphorylates PDCD5 at Ser-119, which leads to PDCD5 destabilization. Overexpression of wild-type PPEF-1, but not inactive PPEF-1D172N, efficiently suppressed CK2α-mediated stabilization of PDCD5 and p53-mediated apoptosis in response to etoposide (ET). Conversely, PPEF-1 knockdown further enhanced genotoxic stress responses. Notably, PPEF-1 suppressed p53-mediated genotoxic stress response via negative regulation of PDCD5. We also determined that overexpression of wild-type PPEF-1, but not inactive PPEF-1D172N, significantly increased tumorigenic growth and chemoresistance of A549 human lung carcinoma cells. Collectively, these data demonstrate that PPEF-1 plays a pivotal role in tumorigenesis of lung cancer cells by reducing PDCD5-mediated genotoxic stress responses. PMID:28051100

  9. Dichlorophen and Dichlorovos mediated genotoxic and cytotoxic assessment on root meristem cells of Allium cepa

    Directory of Open Access Journals (Sweden)

    Sibhghatulla Shaikh

    2012-06-01

    Full Text Available Plants are direct recipients of agro – toxics and therefore important materials for assessing environmental chemicals for genotoxicity. The meristematic mitotic cell of Allium cepa is an efficient cytogenetic material for chromosome aberration assay on environmental pollutants. Onion root tips were grown on moistened filter paper in petri dish at room temperature. Germinated root tips were then exposed to three concentrations of each pesticide for 24 h. About 1 – 2 mm length of root tip was cut, fixed in cornoy’s fixative, hydrolyzed in warm 1 N HCL, stained with acetocarmine and squashed on glass slide. About 3000 cells were scored and classified into interphase and normal or aberrant division stage. Cytotoxicity was determined by comparing the mitotic index (MI of treated cells with that of the negative control. The MI of cells treated with Dichlorophen and Dichlorovos at one or more concentration was half or less than that of control are said to be cytotoxic. Genotoxicity was measured by comparing the number of cells/1000 in aberrant division stages at each dose with the negative control using Mann – Whitney U test. Both Dichlorophen and Dichlorovos are genotoxic at higher concentrations i.e. 0.001%, 0.002% and 0.028%, 0.056% inducing chromosome fragment, chromosome lagging and bridges, stick chromosome and multipolar anaphase.

  10. Microalga Euglena as a bioindicator for testing genotoxic potentials of organic pollutants in Taihu Lake, China.

    Science.gov (United States)

    Li, Mei; Gao, Xiangyu; Wu, Bing; Qian, Xin; Giesy, John P; Cui, Yibin

    2014-05-01

    The microalga Euglena was selected as a bioindicator for determining genotoxicity potencies of organic pollutants in Meiliang Bay of Taihu Lake, Jiangsu, China among seasons in 2008. Several methods, including the comet assay to determine breaks in DNA and quantification of antioxidant enzymes were applied to characterize genotoxic effects of organic extracts of water from Taihu Lake on the flagellated, microalga Euglena gracilis. Contents of photosynthetic pigments, including Chl a, Chl b and carotenoid pigments were inversely proportion to concentrations of organic extracts to which E. gracilis was exposed. Organic extracts of Taihu Lake water also affected activities of superoxide dismutase (SOD) and peroxidase (POD) of E. gracilis. There were no statistically significant differences in SOD activities among seasons except in June but significant differences in POD activities were observed among all seasons. The metrics of DNA fragmentation in the alkaline unwinding assay (Comet assay), olive tail moment (OTM) and tail moment (TM), used as measurement endpoints during the genotoxicity assay were both greater when E. gracilis was exposed to organic of water collected from Taihu Lake among four seasons. It is indicated that the comet assay was useful for determining effects of constituents of organic extracts of water on E. gracilis and this assay was effective as an early warning to organic pollutants.

  11. Genotoxicity studies of glycidol fatty acid ester (glycidol linoleate) and glycidol.

    Science.gov (United States)

    Ikeda, Naohiro; Fujii, Kenkichi; Sarada, Miko; Saito, Hitoshi; Kawabata, Masayoshi; Naruse, Kiyoko; Yuki, Katsuyuki; Nakagiri, Hideaki; Honda, Hiroshi; Tamaki, Yasushi; Nishiyama, Naohiro; Kasamatsu, Toshio

    2012-11-01

    Glycidol fatty acid esters (GEs) are found in refined edible oils. Safety concerns have been alleged due to the possible release of glycidol (G), an animal carcinogen. We evaluated the genotoxic potential of glycidol linoleate (GL), a primary GE found in an edible oil (diacylglycerol oil), and G, using three established genotoxicity tests (a bacterial reverse mutation test, an in vitro chromosomal aberration test, and an in vivo bone marrow micronucleus test) under GLP conditions complying with all OECD guidelines. In the bacterial reverse mutation test, GL and G showed positive responses. The positive responses of GL were less than those of G and observed only in strains detecting point mutations where G showed remarkably positive responses. G was involved in the positive response of GL. In the chromosomal aberration test, GL did not induce chromosome aberrations whereas G induced structural chromosome aberrations in the presence and absence of metabolic activation. In the bone marrow micronucleus test, neither GL nor G induced significant increases of micronucleated immature (polychromatic) erythrocytes in bone marrow of test animals. Based on the above results as well as pertinent information on toxicokinetics, GL itself does not play a key role in genotoxic action.

  12. Can Genotoxic Effect be Model Dependent in Allium Test?-An Evidence

    Directory of Open Access Journals (Sweden)

    Hemant Singh Rathore

    2010-07-01

    Full Text Available Genotoxicity of peracetic acid (PAA has been assessed in two models (protocols of Allium cepa conducting two sets of experiments to know whether the results would be model dependent. One experiment was set as per Fiskesjo's model in which Allium cepa bulbs were grown in five concentrations of peracetic acid (0.039, 0.078, 0.156, 0.312 and 0.625 ppm in tap water. Another experiment was set as per Rank and Nielson's model in which Allium cepa bulbs were first grown in tap water for 24 hours and were then further grown in the same concentrations of peracetic acid as in earlier model. Genotoxic effects of peracetic acid were assessed in both models using usual parameters i.e. shape, colour and length of root tips, mitotic index, chromosomal aberrations and cell death. Magnitude of effect differed significantly in both models. More severe genotoxic effects could be seen in Fiskesjo's model. It is suggested that root primordial cells were in G0 state in Fiskesjo's model, which presumably lacked their defense system, hence were more prone to peracetic acid toxicity. Mitotically dividing root cells in Rank and Nielsen's model were equipped with antioxidant system and were more resistant to peracetic acid

  13. INTERNATIONAL CONFERENCE ON HARMONISATION GUIDELINES ON THE LIMITS OF GENOTOXIC IMPURITIES IN DRUG PRODUCT

    Directory of Open Access Journals (Sweden)

    Malik Ajay

    2012-04-01

    Full Text Available An impurity in a drug substance as defined by the International Conference on Harmonisation (ICH guidelines is any component of the drug substance that is not the chemical entity defined as the drug substance. Similarly, an impurity in a drug product is any component of the drug product that is not the chemical entity defined as the drug substance or an excipient in the drug product. Genotoxic compounds have the potential to damage DNA at any level of exposure and that such damage may lead/contribute to tumour development. Thus for genotoxic carcinogens it is prudent to assume that there is no discernible threshold and that any level of exposure carries a risk. A threshold of toxicological concern (TTC value of 1.5μg/day intake of a genotoxic impurity is considered to be associated with an acceptable risk (excess cancer risk of <1 in 100,000 over a lifetime for most pharmaceuticals. From this threshold value, a permitted level in the active substance can be calculated based on the expected daily dose. Higher limits may be justified under certain conditions such as short-term exposure periods.

  14. Black pepper constituent piperine: genotoxicity studies in vitro and in vivo.

    Science.gov (United States)

    Thiel, Anette; Buskens, Carin; Woehrle, Tina; Etheve, Stéphane; Schoenmakers, Ankie; Fehr, Markus; Beilstein, Paul

    2014-04-01

    Piperine is responsible for the hot taste of black pepper. Publications on genotoxicity of piperine are reported: negative Ames Tests and one in vitro micronucleus test (MNT). In vivo tests were mainly negative. In the majority of the data the administered dose levels did not follow the dose selection requirements of regulatory guidelines of having dose levels up to the maximum tolerated dose (MTD). The only oral high dose studies were a positive in vivo MNT in mice in contrast to a negative in vivo chromosome aberration test in rats. Thus, conflicting results in genotoxicity testing are published. To investigate this further, we administered piperine to mice up to the MTD and determined micronuclei-frequency. Piperine reduces core body temperature and interferes with blood cells both being known to result in irrelevant positive in vivo MNTs. Therefore we added mechanistic endpoints: core body temperature, haematology, erythropoietin level, and organ weights. Additionally an in vitro MNT in Chinese hamster ovary cells was performed. Piperine was negative in the in vitro MNT. It caused significant reduction of core body temperature, decrease of white blood cells and spleen weights but no increase in the micronucleus-frequency. Thus, in our studies piperine was not genotoxic.

  15. 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.

  16. Anti-genotoxic and free-radical scavenging activities of extracts from (Tunisian) Myrtus communis.

    Science.gov (United States)

    Hayder, N; Abdelwahed, A; Kilani, S; Ammar, R Ben; Mahmoud, A; Ghedira, K; Chekir-Ghedira, L

    2004-11-14

    The effect of extracts from leaves of Myrtus communis on the SOS reponse induced by Aflatoxin B1 (AFB1) and Nifuroxazide was investigated in a bacterial assay system, i.e. the SOS chromotest with Escherichia coli PQ37. Aqueous extract, the total flavonoids oligomer fraction (TOF), hexane, chloroform, ethyl acetate and methanol extracts and essential oil obtained from M. communis significantly decreased the SOS response induced by AFB1 (10 microg/assay) and Nifuroxazide (20 microg/assay). Ethyl acetate and methanol extracts showed the strongest inhibition of the induction of the SOS response by the indirectly genotoxic AFB1. The methanol and aqueous extracts exhibited the highest level of protection towards the SOS-induced response by the directly genotoxic Nifuroxazide. In addition to anti-genotoxic activity, the aqueous extract, the TOF, and the ethyl acetate and methanol extracts showed an important free-radical scavenging activity towards the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. These results suggest the future utilization of these extracts as additives in chemoprevention studies.

  17. Photochemical fate and eco-genotoxicity assessment of the drug etodolac

    Energy Technology Data Exchange (ETDEWEB)

    Passananti, Monica [Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Universitario Monte S. Angelo, via Cintia, 4, 80126 Napoli (Italy); Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand (ICCF) UMR 6296, BP 10448, F-63000 Clermont-Ferrand (France); Lavorgna, Margherita [Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Via Vivaldi 43, I-81100 Caserta (Italy); Iesce, Maria Rosaria, E-mail: iesce@unina.it [Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Universitario Monte S. Angelo, via Cintia, 4, 80126 Napoli (Italy); DellaGreca, Marina [Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Universitario Monte S. Angelo, via Cintia, 4, 80126 Napoli (Italy); Brigante, Marcello [Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand (ICCF) UMR 6296, BP 10448, F-63000 Clermont-Ferrand (France); Criscuolo, Emma [Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Via Vivaldi 43, I-81100 Caserta (Italy); Cermola, Flavio [Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Universitario Monte S. Angelo, via Cintia, 4, 80126 Napoli (Italy); Isidori, Marina, E-mail: marina.isidori@unina2.it [Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università di Napoli, Via Vivaldi 43, I-81100 Caserta (Italy)

    2015-06-15

    The photochemical behavior of etodolac was investigated under various irradiation conditions. Kinetic data were obtained after irradiation of 10{sup −4} M aqueous solutions by UVB, UVA and direct exposure to sunlight. The Xenon lamp irradiation was used in order to determine the photodegradation quantum yield under sun-simulated condition (ϕ{sub sun}). The value was determined to be = 0.10 ± 0.01. In order to obtain photoproducts and for mechanistic purposes, experiments were carried out on more concentrated solutions by exposure to sunlight and to UVA and UVB lamps. The drug underwent photooxidative processes following an initial oxygen addition to the double bond of the five membered ring and was mainly converted into a spiro compound and a macrolactam. Ecotoxicity tests were performed on etodolac, its photostable spiro derivative and its sunlight irradiation mixture on two different aquatic trophic levels, plants (algae) and invertebrates (rotifers and crustaceans). Mutagenesis and genotoxicity were detected on bacterial strains. The results showed that only etodolac had long term effects on rotifers although at concentrations far from environmental detection values. A mutagenic and genotoxic potential was found for its derivative. - Highlights: • Photochemical transformation of etodolac occurs in the environment. • Etodolac was slightly toxic in the long term for some aquatic organisms. • A mutagenic and genotoxic potential was found for etodolac photostable derivative.

  18. 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.

  19. Titanium dioxide nanoparticles exhibit genotoxicity and impair DNA repair activity in A549 cells.

    Science.gov (United States)

    Jugan, Mary-Line; Barillet, Sabrina; Simon-Deckers, Angelique; Herlin-Boime, Nathalie; Sauvaigo, Sylvie; Douki, Thierry; Carriere, Marie

    2012-08-01

    Titanium dioxide nanoparticles (TiO(2)-NPs) are produced in large quantities, raising concerns about their impact for human health. The aim of this study was to deeply characterize TiO(2)-NPs genotoxic potential to lung cells, and to link genotoxicity to physicochemical characteristics, e.g., size, specific surface area, crystalline phase. A549 cells were exposed to a panel of TiO(2)-NPs with diameters ranging from 12 to 140 nm, either anatase or rutile. A set of complementary techniques (comet and micronucleus assays, gamma-H2AX immunostaining, 8-oxoGuanine analysis, H2-DCFDA, glutathione content, antioxidant enzymes activities) allowed us to demonstrate that small and spherical TiO(2)-NPs, both anatase and rutile, induce single-strand breaks and oxidative lesions to DNA, together with a general oxidative stress. Additionally we show that these NPs impair cell ability to repair DNA, by inactivation of both NER and BER pathways. This study thus confirms the genotoxic potential of TiO(2)-NPs, which may preclude their mutagenicity and carcinogenicity.

  20. Evaluation of genotoxic activity of tenofovir disoproxil fumarate in human peripheral lymphocytes

    Directory of Open Access Journals (Sweden)

    Kubra Kurt

    2016-06-01

    Full Text Available Purpose: Antiretroviral drugs used in the treatment of HIV (Human Immunodeficiency Virus iinfection, treat by preventing the proliferation of HIV in human body. People with HIV have to use this drugs for lifelong because of inability of the drugs to eradicate the viruses. In this study, we investigated the in vitro genotoxic activity of tenofovir disoproxil fumarate one of the antiretroviral drugs, in human peripheral lymphocytes. Material and Methods: The cells were treated with four different concentrations of tenofovir disoproxil fumarate for 24 and 48 hours. The levels of sister chromatid exchanges, chromosomal aberrations, and micronucleus in the cells were examined for the genotoxic activity of tenofovir disoproxil fumarate. Mitotic index, proliferation index, and nucleer division index of treated cells were also determined for the cytotoxic effect of tenofovir disoproxil fumarate. Results: There was no significant differences in the level of sister chromatid exchanges, chromosomal aberrations, and micronucleus in human lyphocytes treated with all concetrations of tenofovir disoproxil fumarate for all treatment period as compared to control group. Similarly, it was observed that treatment of tenofovir disoproxil fumarate did not affect the mitotic index, proliferation index, and nucleer division index values. Conclusion: As a result, in this study, it is demonstrated that tenofovir disoproxil fumarate did not have genotoxic or cytotoxic effect in the human peripheral lymphocytes. [Cukurova Med J 2016; 41(2.000: 229-235