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

Directory of Open Access Journals (Sweden)

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.

A diet high in fat and meat but low in dietary fibre increases the genotoxic potential of 'faecal water'

DEFF Research Database (Denmark)

Rieger, Martin A.; Parlesak, Alexandr; Pool-Zobel, Beatrice

1999-01-01

To determine the effects of different diets on the genotoxicity of human faecal water, a diet rich in fat, meat and sugar but poor in vegetables and free of wholemeal products (diet 1) was consumed by seven healthy volunteers over a period of 12 days. One week after the end of this period......, the volunteers started to consume a diet enriched with vegetables and wholemeal products but poor in fat and meat (diet 2) over a second period of 12 days. The genotoxic effect of faecal waters obtained after both diets was assessed with the single cell gel electrophoresis (Comet assay) using the human colon...... and purine bases revealed no differences after pretreatment with both types of faecal water. The results indicate that diets high in fat and meat but low in dietary fibre increase the genotoxicity of faecal water to colonic cells and may contribute to an enhanced risk of colorectal cancer....

CAD for CT colonography: toward a preparation-independent scheme

International Nuclear Information System (INIS)

Naeppi, J.

2007-01-01

Computer-aided detection (CAD) systems can be used to automatically detect and display the locations of polyps and masses in computed tomographic colonography (CTC) data for assisting radiologists' image interpretation. Rapid technical advancements over the last few years have established a fundamental CAD scheme for CTC that includes the steps of colon extraction, polyp detection, and false-positive (FP) reduction. Several CAD prototype systems have demonstrated clinically acceptable high polyp detection sensitivity with relatively few FP detections in cathartic CTC, and observer studies have demonstrated the potential benefit of such systems in improving the accuracy and consistency of radiologists' detection performance. Some CAD prototype systems have also demonstrated promising performance in reduced cathartic and non-cathartic CTC. Recent advancements suggest that CAD systems can soon be expected to provide a preparation-independent scheme that can yield consistently high detection sensitivity with moderately low FP rate not only with cathartic CTC protocols but over a wide range of cathartic, reduced cathartic, and non-cathartic CTC protocols. (orig.)

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...

Limited ability of DNA polymerase kappa to suppress benzo[a]pyrene-induced genotoxicity in vivo.

Science.gov (United States)

Masumura, Kenichi; Toyoda-Hokaiwado, Naomi; Niimi, Naoko; Grúz, Petr; Wada, Naoko A; Takeiri, Akira; Jishage, Kou-Ichi; Mishima, Masayuki; Nohmi, Takehiko

2017-12-01

DNA polymerase kappa (Polk) is a specialized DNA polymerase involved in translesion DNA synthesis. To understand the protective roles against genotoxins in vivo, we established inactivated Polk knock-in gpt delta (inactivated Polk KI) mice that possessed reporter genes for mutations and expressed inactive Polk. In this study, we examined genotoxicity of benzo[a]pyrene (BP) to determine whether Polk actually suppressed BP-induced genotoxicity as predicted by biochemistry and in vitro cell culture studies. Seven-week-old inactivated Polk KI and wild-type (WT) mice were treated with BP at doses of 5, 15, or 50 mg/(kg·day) for three consecutive days by intragastric gavage, and mutations in the colon and micronucleus formation in the peripheral blood were examined. Surprisingly, no differences were observed in the frequencies of mutations and micronucleus formation at 5 or 50 mg/kg doses. Inactivated Polk KI mice exhibited approximately two times higher gpt mutant frequency than did WT mice only at the 15 mg/kg dose. The frequency of micronucleus formation was slightly higher in inactivated Polk KI than in WT mice at the same dose, but it was statistically insignificant. The results suggest that Polk has a limited ability to suppress BP-induced genotoxicity in the colon and bone marrow and also that the roles of specialized DNA polymerases in mutagenesis and carcinogenesis should be examined not only by in vitro assays but also by in vivo mouse studies. We also report the spontaneous mutagenesis in inactivated Polk KI mice at young and old ages. Environ. Mol. Mutagen. 58:644-653, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

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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.

Increasing fish consumption does not affect genotozicity markers in the colon in an intervention study

NARCIS (Netherlands)

Pot, G.K.; Habermann, N.; Majsak-Newman, G.; Harvey, L.J.; Geelen, A.; Witteman, B.J.M.; Meeberg, van de P.C.; Hart, A.R.; Schaafsma, G.; Hooiveld, G.J.E.J.; Glei, M.; Lund, E.K.; Pool-Zobel, B.L.; Kampman, E.

2010-01-01

Observational studies suggest that fish consumption is associated with a decreased colorectal cancer (CRC) risk. A possible mechanism by which fish could reduce CRC risk is by decreasing colonic genotoxicity. However, concerns have also been raised over the levels of toxic compounds found in mainly

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.

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...... signaling. These integumentary characters have been difficult to study because of extensive postmortem color fading and shrinkage in museum specimens. Here I provide the first detailed description of head color and caruncles of the Greater Yellow-headed Vulture (C. melambrotus) from freshly collected...

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

International Nuclear Information System (INIS)

Melis, Joost P.M.; Speksnijder, Ewoud N.; Kuiper, Raoul V.; Salvatori, Daniela C.F.; Schaap, Mirjam M.; Maas, Saskia; Robinson, Joke; Verhoef, Aart; Benthem, Jan van; Luijten, Mirjam; Steeg, Harry van

2013-01-01

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.

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. . ©2015 American Association for Cancer Research.

Genotoxic effects of environmental pollutants genotoxic monitoring and detection of antigenotoxic effects

International Nuclear Information System (INIS)

Simic, D.; Knezevic-Vukcevic, J.; Vukovi -Gacic, B.; Mitic, D.; Beric, T.; Nikolic, B.; Stanojevic, J.; Stankovic, S.

2002-01-01

The control of genotoxic agents mass release, which can adversely affect the ecosystem stability and human health is of the greatest importance. Therefore, it is necessary to seriously elaborate the strategy of genotoxic monitoring and relevant legislation. Additional approach is the study and dietary use of antigenotoxic plant substances for prevention of mutation-related diseases. (author)

Genotoxic effects of environmental pollutants genotoxic monitoring and detection of antigenotoxic effects

Energy Technology Data Exchange (ETDEWEB)

Simic, D; Knezevic-Vukcevic, J; Vukovi -Gacic, B; Mitic, D; Beric, T; Nikolic, B; Stanojevic, J; Stankovic, S [Faculty of Biology, University of Belgrade, Belgrade (Yugoslavia)

2002-05-01

The control of genotoxic agents mass release, which can adversely affect the ecosystem stability and human health is of the greatest importance. Therefore, it is necessary to seriously elaborate the strategy of genotoxic monitoring and relevant legislation. Additional approach is the study and dietary use of antigenotoxic plant substances for prevention of mutation-related diseases. (author)

A sucrose-rich diet induces mutations in the rat colon

DEFF Research Database (Denmark)

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

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...... 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...

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.

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.

Genotoxicity evaluation of alpha-linolenic acid-diacylglycerol oil

Directory of Open Access Journals (Sweden)

Hiroshi Honda

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. Keywords: Alpha-linolenic acid-rich diacylglycerol, Diacylglycerol, Alpha-linolenic acid, Fatty acid composition, Genotoxicity

Genotoxicity of metal nanoparticles.

Science.gov (United States)

Xie, Hong; Mason, Michael M; Wise, John Pierce

2011-01-01

Nanotechnology is currently used in industry, medicine, and military applications, as well as in more than 300 commercial products. Yet, the same properties that make these particles exciting for technology also make them daunting public health concerns because their toxicity is unknown and relatively unexplored. Increased attention is being placed on the study of metal particle genotoxicity; however, a lot of unknowns remain about their effects and the mechanisms. In this article, we highlight some metal and metal oxide nanoparticles of interest and discuss the current in vivo and in vitro studies of genotoxic effects. Many metal nanoparticles were found to cause chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. Inconsistencies are found in the literature, however, thus drawing conclusions is difficult due to a variety of factors. Therefore, the areas requiring further attention are highlighted and recommendations to improve our understanding of the genotoxic potential are addressed.

Genotoxicity of 1,3-dichloro-2-propanol in the SOS chromotest and in the Ames test. Elucidation of the genotoxic mechanism.

Science.gov (United States)

Hahn, H; Eder, E; Deininger, C

1991-01-01

1,3-Dichloro-2-propanol (1,3-DCP-OH, glycerol dichlorohydrin) is of great importance in many industrial processes and has been detected in foodstuffs, in particular in soup spices and instant soups. It has been shown to be carcinogenic, genotoxic and mutagenic. Its genotoxic mechanisms are, however, not yet entirely understood. We have investigated whether alcohol dehydrogenase (ADH) catalysed activation to the highly mutagenic and carcinogenic 1,3-dichloroacetone or formation of epichlorohydrin or other genotoxic compounds play a role for mutagenicity and genotoxicity. In our studies, no indications of ADH catalysed formation of 1,3-dichloropropane could be found, although we could demonstrate a clear activation by ADH in the case of 2-chloropropenol. Formation of allyl chloride could also be excluded. We found, however, clear evidence that epichlorohydrin formed chemically in the buffer and medium used in the test is responsible for genotoxicity. No indication was found that enzymatic formation of epichlorohydrin plays a role. Additional mutagenicity and genotoxicity studies with epichlorohydrin also confirmed the hypothesis that genotoxic effects of 1,3-DCP-OH depend on the chemical formation of epichlorohydrin.

In vivo assessment of genotoxic, antigenotoxic and anticarcinogenic activities of Solanum lycocarpum fruits glycoalkaloidic extract.

Directory of Open Access Journals (Sweden)

Carla Carolina Munari

Full Text Available The fruits of Solanum lycocarpum, known as wolf-fruit, are used in folk medicine, and because of that we have evaluated both the genotoxic potential of its glycoalkaloidic extract (SL and its influence on the genotoxicity induced by methyl methanesulfonate. Furthermore, the potential blocking effect of SL intake in the initial stage of colon carcinogenesis in Wistar rats was investigated in a short-term (4-week bioassay using aberrant crypt foci (ACF as biomarker. The genotoxic potential was evaluated using the Swiss mice peripheral blood micronucleus test. The animals were treated with different doses of SL (15, 30 and 60 mg/kg b.w. for 14 days, and the peripheral blood samples were collected at 48 h, 7 days and 14 days after starting the treatment. For antigenotoxicity assessment, MMS was administered on the 14th day, and after 24 h the harvesting of bone marrow and liver cells was performed, for the micronucleus and comet assays, respectively. In the ACF assay, male Wistar rats were given four subcutaneous injections of the carcinogen 1,2-dimethylhydrazine (DMH, 40 mg/kg b.w., twice a week, during two weeks to induce ACF. The treatment with SL (15, 30 and 60 mg/kg b.w. was given for four weeks during and after carcinogen treatment to investigate the potential beneficial effects of SL on DMH-induced ACF. The results demonstrated that SL was not genotoxic in the mouse micronucleus test. In animals treated with SL and MMS, the frequencies of micronucleus and extensions of DNA damage were significantly reduced in comparison with the animals receiving only MMS. Regarding the ACF assay, SL significantly reduced the frequency of ACF induced by DMH.

Effects of habitat and time of day on flock size of Turkey Vultures in Cuba (Cathartes aura

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Piotr Tryjanowski

2018-01-01

Full Text Available In agricultural landscapes, the Turkey Vulture Cathartes aura feeds mainly on carcases of domestic animals. In spring 2017, data on 214 flocks of Turkey vultures were collected in a road survey in Cuba (in total 2384 km. Turkey Vultures were found to be common accross Cuba, but flock size varied between habitats, reaching a maximum of 43 in valleys and 31 in agricultural landscapes with domestic animal farms. Vultures were active throughout the day, but the time of day did not significantly affect flock size. This study corroborates previous studies which suggested that carrion resources located in agricultural habitats and river valleys is crucial for the continued survival of this still abundant species. Changes in Cuba’s socio-political system in the near future will likely impact agricultural practices, and this in turn will likely affect Turkey Vultures. Our study may serve as a baseline against which future population changes and flocking behaviour of Turkey Vultures can be compared.

Flow cytometry based micronucleus assay for evaluation of genotoxic potential of 2-ACBs in hepatic cells HepG2

International Nuclear Information System (INIS)

Barbezan, Angélica B.; Santos, Carla J.B.; Carvalho, Luma R.; Vieira, Daniel P.; Villavicêncio, Anna L.C.H.; Santelli, Glaucia M.M.

2017-01-01

Food irradiation is approved for use in more than 60 countries for applications and purposes in a wide variety of foods, being an effective and safe method for preservation and long-term storage. 2-Alkylcyclobutanones (2-ACBs) are the only known radiolytic products generated from foods that contain fatty acids (Triglycerides) when irradiated. The acids analyzed in this study are palmitic and stearic, which when irradiated form 2-Dodecylcyclobutanones (2-dDCB) and 2-Tetradecylcyclobutanone (2-tDCB). Part of the 2-ACBs ingested is excreted through feces and part is deposited in adipose tissues. In vitro studies so far have been only in colon cells. The work used a human hepatoma cell line (HepG2) since the accumulation of fat in this organ is quite common. Micronucleus test was selected to evaluate possible genotoxic effects of 2-dDCB and 2-tDCB compounds when exposed to high concentrations (447, 1422 and 2235 μM) for 4 and 24 hours. Tests were performed in quadriplicates using flow cytometric analysis. None detectable genotoxic damage was observed after 4 hours of exposure to the compounds, and cytotoxic effects were only significant at the highest concentration (2235 μM) of 2-dDCB. After 24 hours of exposure, slight genotoxic damage was observed at all concentrations evaluated, and cytotoxic effects were only present when exposed to compound 2-tDCB. Although there is a genotoxic and cytotoxic effect in some of the situations tested, the two compounds predominantly induced proliferation reduction effects of this hepatic tumor cell line. (author)

Flow cytometry based micronucleus assay for evaluation of genotoxic potential of 2-ACBs in hepatic cells HepG2

Energy Technology Data Exchange (ETDEWEB)

Barbezan, Angélica B.; Santos, Carla J.B.; Carvalho, Luma R.; Vieira, Daniel P.; Villavicêncio, Anna L.C.H., E-mail: abarbezan@ipen.br [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil); Santelli, Glaucia M.M. [Universidade de São Paulo (USP), SP (Brazil). Departamento de Biologia Celular e do Desenvolvimento

2017-07-01

Food irradiation is approved for use in more than 60 countries for applications and purposes in a wide variety of foods, being an effective and safe method for preservation and long-term storage. 2-Alkylcyclobutanones (2-ACBs) are the only known radiolytic products generated from foods that contain fatty acids (Triglycerides) when irradiated. The acids analyzed in this study are palmitic and stearic, which when irradiated form 2-Dodecylcyclobutanones (2-dDCB) and 2-Tetradecylcyclobutanone (2-tDCB). Part of the 2-ACBs ingested is excreted through feces and part is deposited in adipose tissues. In vitro studies so far have been only in colon cells. The work used a human hepatoma cell line (HepG2) since the accumulation of fat in this organ is quite common. Micronucleus test was selected to evaluate possible genotoxic effects of 2-dDCB and 2-tDCB compounds when exposed to high concentrations (447, 1422 and 2235 μM) for 4 and 24 hours. Tests were performed in quadriplicates using flow cytometric analysis. None detectable genotoxic damage was observed after 4 hours of exposure to the compounds, and cytotoxic effects were only significant at the highest concentration (2235 μM) of 2-dDCB. After 24 hours of exposure, slight genotoxic damage was observed at all concentrations evaluated, and cytotoxic effects were only present when exposed to compound 2-tDCB. Although there is a genotoxic and cytotoxic effect in some of the situations tested, the two compounds predominantly induced proliferation reduction effects of this hepatic tumor cell line. (author)

DNA adductomics to study the genotoxic effects of red meat consumption with and without added animal fat in rats.

Science.gov (United States)

Hemeryck, Lieselot Y; Van Hecke, Thomas; Vossen, Els; De Smet, Stefaan; Vanhaecke, Lynn

2017-09-01

Digestion of red and processed meat has been linked to the formation of genotoxic N-nitroso compounds (NOCs) and lipid peroxidation products (LPOs) in the gut. In this study, rats were fed a meat based diet to compare the possible genotoxic effects of red vs. white meat, and the interfering role of dietary fat. To this purpose, liver, duodenum and colon DNA adductomes were analyzed with UHPLC-HRMS. The results demonstrate that the consumed meat type alters the DNA adductome; the levels of 22 different DNA adduct types significantly increased upon the consumption of beef (compared to chicken) and/or lard supplemented beef or chicken. Furthermore, the chemical constitution of the retrieved DNA adducts hint at a direct link with an increase in NOCs and LPOs upon red (and processed) meat digestion, supporting the current hypotheses on the causal link between red and processed meat consumption and the development of colorectal cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

In silico prediction of genotoxicity.

Science.gov (United States)

Wichard, Jörg D

2017-08-01

The in silico prediction of genotoxicity has made considerable progress during the last years. The main driver for the pharmaceutical industry is the ICH M7 guideline about the assessment of DNA reactive impurities. An important component of this guideline is the use of in silico models as an alternative approach to experimental testing. The in silico prediction of genotoxicity provides an established and accepted method that defines the first step in the assessment of DNA reactive impurities. This was made possible by the growing amount of reliable Ames screening data, the attempts to understand the activity pathways and the subsequent development of computer-based prediction systems. This paper gives an overview of how the in silico prediction of genotoxicity is performed under the ICH M7 guideline. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantitative genotoxicity assays for analysis of medicinal plants: A systematic review.

Science.gov (United States)

Sponchiado, Graziela; Adam, Mônica Lucia; Silva, Caroline Dadalt; Soley, Bruna Silva; de Mello-Sampayo, Cristina; Cabrini, Daniela Almeida; Correr, Cassyano Januário; Otuki, Michel Fleith

2016-02-03

Medicinal plants are known to contain numerous biologically active compounds, and although they have proven pharmacological properties, they can cause harm, including DNA damage. Review the literature to evaluate the genotoxicity risk of medicinal plants, explore the genotoxicity assays most used and compare these to the current legal requirements. A quantitative systematic review of the literature, using the keywords "medicinal plants", "genotoxicity" and "mutagenicity", was undertakenQ to identify the types of assays most used to assess genotoxicity, and to evaluate the genotoxicity potential of medicinal plant extracts. The database searches retrieved 2289 records, 458 of which met the inclusion criteria. Evaluation of the selected articles showed a total of 24 different assays used for an assessment of medicinal plant extract genotoxicity. More than a quarter of those studies (28.4%) reported positive results for genotoxicity. This review demonstrates that a range of genotoxicity assay methods are used to evaluate the genotoxicity potential of medicinal plant extracts. The most used methods are those recommended by regulatory agencies. However, based on the current findings, in order to conduct a thorough study concerning the possible genotoxic effects of a medicinal plant, we indicate that it is important always to include bacterial and mammalian tests, with at least one in vivo assay. Also, these tests should be capable of detecting outcomes that include mutation induction, clastogenic and aneugenic effects, and structural chromosome abnormalities. In addition, the considerable rate of positive results detected in this analysis further supports the relevance of assessing the genotoxicity potential of medicinal plants. Copyright © 2016. Published by Elsevier Ireland Ltd.

"Aspartame: A review of genotoxicity data".

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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. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

GENOTOXICITY OF TOBACCO SMOKE AND TOBACCO SMOKE CONDENSATE: A REVIEW

Science.gov (United States)

Genotoxicity of Tobacco Smoke and Tobacco Smoke Condensate: A ReviewAbstractThis report reviews the literature on the genotoxicity of main-stream tobacco smoke and cigarette smoke condensate (CSC) published since 1985. CSC is genotoxic in nearly all systems in which it h...

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.

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. © 2013 Wiley Periodicals, Inc.

Molecular Basis of Alcohol-Related Gastric and Colon Cancer.

Science.gov (United States)

Na, Hye-Kyung; Lee, Ja Young

2017-05-24

Many meta-analysis, large cohort studies, and experimental studies suggest that chronic alcohol consumption increases the risk of gastric and colon cancer. Ethanol is metabolized by alcohol dehydrogenases (ADH), catalase or cytochrome P450 2E1 (CYP2E1) to acetaldehyde, which is then further oxidized to acetate by aldehyde dehydrogenase (ALDH). Acetaldehyde has been classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen to humans. The acetaldehyde level in the stomach and colon is locally influenced by gastric colonization by Helicobacter pylori or colonic microbes, as well as polymorphisms in the genes encoding tissue alcohol metabolizing enzymes, especially ALDH2. Alcohol stimulates the uptake of carcinogens and their metabolism and also changes the composition of enteric microbes in a way to enhance the aldehyde level. Alcohol also undergoes chemical coupling to membrane phospholipids and disrupts organization of tight junctions, leading to nuclear translocation of β-catenin and ZONAB, which may contributes to regulation of genes involved in proliferation, invasion and metastasis. Alcohol also generates reactive oxygen species (ROS) by suppressing the expression of antioxidant and cytoprotective enzymes and inducing expression of CYP2E1 which contribute to the metabolic activation of chemical carcinogens. Besides exerting genotoxic effects by directly damaging DNA, ROS can activates signaling molecules involved in inflammation, metastasis and angiogenesis. In addition, alcohol consumption induces folate deficiency, which may result in aberrant DNA methylation profiles, thereby influencing cancer-related gene expression.

Genotoxicity of 11 heavy metals detected as food contaminants in two human cell lines.

Science.gov (United States)

Kopp, B; Zalko, D; Audebert, M

2018-04-01

Heavy metals, such as arsenic (As), antimony (Sb), barium (Ba), cadmium (Cd), cobalt (Co), germanium (Ge), lead (Pb), nickel (Ni), tellurium (Te), and vanadium (V) are widely distributed in the environment and in the food chain. Human exposure to heavy metals through water and food has been reported by different international agencies. Although some of these heavy metals are essential elements for human growth and development, they may also be toxic at low concentrations due to indirect mechanisms. In this study, the genotoxic and cytotoxic properties of 15 different oxidation statuses of 11 different heavy metals were investigated using high-throughput screening (γH2AX assay) in two human cell lines (HepG2 and LS-174T) representative of target organs (liver and colon) for food contaminants. Base on their lowest observed adverse effect concentration, the genotoxic potency of each heavy metal in each cell line was ranked in decreasing order, NaAsO 2  > CdCl 2  > PbCl 2 (only in LS-174T cells) > As 2 O 5  > SbCl 3  > K 2 TeO 3  > As 2 O 3 . No significant genotoxicity was observed with the other heavy metals tested. Cell viability data indicate that several heavy metals (As, Cd, Co, Ni, Sb, and Te) induce cytotoxicity at high concentrations, whereas an increase in the number of cells was observed for lead concentrations >100 µM in both cell lines tested, suggesting that lead stimulates cell growth. All these results highlight the possible human health hazards associated with the presence of heavy metals present in food. Environ. Mol. Mutagen. 59:202-210, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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.

Genotoxicity of 2-bromo-3′-chloropropiophenone

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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

Genotoxicity of 2-bromo-3′-chloropropiophenone

International Nuclear Information System (INIS)

Meng, Fanxue; Yan, Jian; Li, Yan; Fu, Peter P.; Fossom, Linda H.; Sood, Ramesh K.; Mans, Daniel J.; Chu, Pei-I; Moore, Martha M.; Chen, Tao

2013-01-01

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

Genotoxic effects of high dose rate X-ray and low dose rate gamma radiation in ApcMin/+ mice.

Science.gov (United States)

Graupner, Anne; Eide, Dag M; Brede, Dag A; Ellender, Michele; Lindbo Hansen, Elisabeth; Oughton, Deborah H; Bouffler, Simon D; Brunborg, Gunnar; Olsen, Ann Karin

2017-10-01

Risk estimates for radiation-induced cancer in humans are based on epidemiological data largely drawn from the Japanese atomic bomb survivor studies, which received an acute high dose rate (HDR) ionising radiation. Limited knowledge exists about the effects of chronic low dose rate (LDR) exposure, particularly with respect to the application of the dose and dose rate effectiveness factor. As part of a study to investigate the development of colon cancer following chronic LDR vs. acute HDR radiation, this study presents the results of genotoxic effects in blood of exposed mice. CBAB6 F1 Apc +/+ (wild type) and Apc Min/+ mice were chronically exposed to estimated whole body absorbed doses of 1.7 or 3.2 Gy 60 Co-γ-rays at a LDR (2.2 mGy h -1 ) or acutely exposed to 2.6 Gy HDR X-rays (1.3 Gy min -1 ). Genotoxic endpoints assessed in blood included chromosomal damage (flow cytometry based micronuclei (MN) assay), mutation analyses (Pig-a gene mutation assay), and levels of DNA lesions (Comet assay, single-strand breaks (ssb), alkali labile sites (als), oxidized DNA bases). Ionising radiation (ca. 3 Gy) induced genotoxic effects dependent on the dose rate. Chromosomal aberrations (MN assay) increased 3- and 10-fold after chronic LDR and acute HDR, respectively. Phenotypic mutation frequencies as well as DNA lesions (ssb/als) were modulated after acute HDR but not after chronic LDR. The Apc Min/+ genotype did not influence the outcome in any of the investigated endpoints. The results herein will add to the scant data available on genotoxic effects following chronic LDR of ionising radiation. Environ. Mol. Mutagen. 58:560-569, 2017. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

The genotoxic contribution of wood smoke to indoor respirable suspended particles

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Boone, P.M. (John B. Pierce Foundation Laboratory, New Haven, CT (USA)); Rossman, T.G. (New York Univ. Medical Center, New York (USA)); Daisey, J.M. (Lawrence Berkeley Laboratory, CA (USA))

1989-01-01

The effect of wood burning stoves on the genotoxicity of indoor respirable organic matter was investigated for four homes during the winter and spring of 1986. Paired samples, one collected when the stove was not used and one when wood was burned, were extracted with dichloromethane and acetone. Aliquots of the dichloromethane extracts were analyzed with and without metabolic activation using the Microscreen bioassay. The Microscreen is a rapid, sensitive bioassay which measures a broad genotoxic endpoint, {lambda}-prophage induction. Per nanogram of organic material, wood smoke proved to be a major source of indirect (observed with metabolic activation) but not direct genotoxins in homes. The increase in indirect genotoxicity for extracts from aerosol containing wood smoke is probably due to higher concentrations of polycyclic aromatic hydrocarbons in the wood smoke aerosol as well as other unidentified classes. The direct genotoxicity observed for extracts of aerosol not containing wood smoke decreased with metabolic activation. This direct genotoxicity may be related to cooking activities in the homes. The trends in genotoxicity observed per nanogram of organic material are more pronounced when expressed per m{sup 3} of air due to the higher percentage of extractable material in aerosol containing wood smoke.

Enhancement of colon carcinogenesis by the combination of indole-3 carbinol and synbiotics in hemin-fed rats.

Science.gov (United States)

de Moura, Nelci A; Caetano, Brunno F R; de Moraes, Leonardo N; Carvalho, Robson F; Rodrigues, Maria A M; Barbisan, Luis F

2018-02-01

The risk of developing colorectal cancer (CRC) could be associated with red and processed meat intake. Experimental data supports that hemin iron, found abundantly in red meat, promotes CRC in mice and rats, while indole-3 carbinol (I3C) and synbiotics (syn) exert anti-carcinogenic activities in most studies of colon carcinogenesis. This study aimed to investigate the modifying effects of I3C and syn (inulin + Bifidobacterium lactis), given separately or together, on dimethylhidrazine (DMH)-induced colon carcinogenesis in hemin-fed rats. All animals were given four subcutaneous DMH injections and then, two weeks after carcinogen exposure, they began a basal diet containing hemin, hemin + I3C, hemin + syn, or hemin + I3C + syn for 23 weeks. The combination of I3C + syn significantly increased fecal water genotoxicity, tumor volume and invasiveness when compared to the hemin-fed control group. The groups fed I3C or syn alone had a significant reduction in the number of preneoplastic aberrant crypt foci (ACF) lesions compared to the hemin-fed group. Dietary I3C also reduced fecal water genotoxicity. Gene expression analysis of colorectal tumors demonstrated that the combination of dietary I3C + syn increased transcript levels for Raf1 and decreased tumor progression and invasiveness related to the genes Cdh1 and Appl1. This analysis also revealed that the Tnf and Cdh1 genes were significantly up- and down-regulated, respectively, in tumors of rats that received I3C, in comparison with the hemin-fed group. These findings reveal that the joint administration of I3C and syn enhanced the development of colon tumors induced by DMH in hemin-fed rats, while they potentially reduced ACF development when given alone. Copyright © 2017 Elsevier Ltd. All rights reserved.

METABOLISM, GENOTOXICITY, AND CARCINOGENICITY OF COMFREY

Science.gov (United States)

Mei, Nan; Guo, Lei; Fu, Peter P.; Fuscoe, James C.; Luan, Yang; Chen, Tao

2018-01-01

Comfrey has been consumed by humans as a vegetable and a tea and used as an herbal medicine for more than 2000 years. Comfrey, however, produces hepatotoxicity in livestock and humans and carcinogenicity in experimental animals. Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7-acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine, lycopsamine, myoscorpine, symlandine, symphytine, and symviridine. The mechanisms underlying comfrey-induced genotoxicity and carcinogenicity are still not fully understood. The available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development. Genotoxicities attributed to comfrey and riddelliine (a representative genotoxic PA and a proven rodent mutagen and carcinogen) are discussed in this review. Both of these compounds induced similar profiles of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and similar mutation spectra. Further, the two agents share common mechanisms of drug metabolism and carcinogenesis. Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be responsible for comfrey-induced toxicity and tumor induction. PMID:21170807

Metabolism, genotoxicity, and carcinogenicity of comfrey.

Science.gov (United States)

Mei, Nan; Guo, Lei; Fu, Peter P; Fuscoe, James C; Luan, Yang; Chen, Tao

2010-10-01

Comfrey has been consumed by humans as a vegetable and a tea and used as an herbal medicine for more than 2000 years. Comfrey, however, produces hepatotoxicity in livestock and humans and carcinogenicity in experimental animals. Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7-acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine, lycopsamine, myoscorpine, symlandine, symphytine, and symviridine. The mechanisms underlying comfrey-induced genotoxicity and carcinogenicity are still not fully understood. The available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development. Genotoxicities attributed to comfrey and riddelliine (a representative genotoxic PA and a proven rodent mutagen and carcinogen) are discussed in this review. Both of these compounds induced similar profiles of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and similar mutation spectra. Further, the two agents share common mechanisms of drug metabolism and carcinogenesis. Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be responsible for comfrey-induced toxicity and tumor induction.

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.

Hepatotoxicity and genotoxicity of gasoline fumes in albino rats

Directory of Open Access Journals (Sweden)

Folarin O. Owagboriaye

2017-09-01

Full Text Available Toxic effects of gasoline fumes have been reported, but evidence of its hepatotoxicity and genotoxicity are rare. Therefore, this study assesses hepatotoxicity and genotoxicity of gasoline fumes on forty Albino rats randomly assigned to five experimental treatments (T with eight rats per treatment (T1, T2, T3, T4 and T5. T1(Control was housed in a section of experimental animal house free from gasoline fumes while T2, T3, T4 and T5 were exposed to gasoline fumes in exposure chambers for one, three, five and nine hours daily respectively for twelve weeks. Serum alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP and histopathological examination of the liver tissues were used as diagnostic markers to assess liver dysfunction. Genotoxicity test was conducted on the lung tissues using randomly amplified polymorphic DNA fingerprinting polymerase chain reaction (RAPD PCR technique. Significant increase (p < 0.05 in the level of ALT, AST and ALP for T2, T3, T4 and T5 compared to T1 were recorded. Photomicrograph examination of the liver sections of T1 showed hepatic tissue with normal liver cell architecture while that of T2, T3, T4 and T5 revealed degenerative changes in the ultrastructural integrity of the hepatic cells. Genotoxicity test revealed DNA bands at a reducing intensity from T1 to T5. Dendrogram showed DNA damage in the lungs of T3, T4 and T5 were closely similar and the genotoxic impact was more in T3. Frequent exposure to gasoline fumes was observed to induce hepatoxicity and genotoxicity, hence impairing the normal liver function and gene structure.

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

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.

Assessment of Genotoxicity of Ionizing radiation using Tradescantia-Comet assay

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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

Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts.

Science.gov (United States)

Waly, Mostafa I; Al-Rawahi, Amani S; Al Riyami, Marwa; Al-Kindi, Mohamed A; Al-Issaei, Halima K; Farooq, Sardar A; Al-Alawi, Ahmed; Rahman, Mohammad S

2014-02-18

Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon. Eighty Sprague-Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation. Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM. The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities.

The use of ex vivo human skin tissue for genotoxicity testing

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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

The use of ex vivo human skin tissue for genotoxicity testing

International Nuclear Information System (INIS)

Reus, Astrid A.; Usta, Mustafa; Krul, Cyrille A.M.

2012-01-01

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

Inhibitory effects of Baccharis dracunculifolia on 1,2-dimethylhidrazine-induced genotoxicity and preneoplastic lesions in rat colon.

Science.gov (United States)

Munari, Carla C; Furtado, Ricardo A; Santiago, Mirian L; Manhas, Simony S; Bastos, Jairo K; Tavares, Denise C

2014-07-01

Baccharis dracunculifolia (Asteraceae), the main botanical source of green propolis, also known as 'alecrim-do-campo' and 'vassourinha', is a shrub of the Brazilian 'cerrado' and is native to the South and Southeast of Brazil. The effects of B. dracunculifolia ethyl acetate extract (Bd-EAE) were evaluated on the 1,2-dimethylhydrazine (DMH)-induced DNA damage and aberrant crypt foci (ACF) in the colon of male Wistar rats by the comet and ACF assays, respectively. The animals were treated by gavage with doses of 6, 12, and 24 mg/kg body weight/day. Animals were also administered a single subcutaneous injection of 40 mg/kg DMH and were killed after 4 h for evaluation of DNA damage. Also, two doses of 40 mg/kg of DMH were administered weekly for 2 weeks, and animals were killed 2 weeks after the last injection for evaluation of ACF development in the colon. The results showed a significant reduction in the frequency of DNA damage and ACF in the group treated with the Bd-EAE plus DMH in comparison with those treated with DMH alone, suggesting that Bd-EAE reduced DNA damage and suppressed the formation of ACF and also exerted a protective affect against colon carcinogenesis.

Genotoxicity and ELF-magnetic fields: a review through the micronucleus assay

International Nuclear Information System (INIS)

Alcaraz, M.; Andreu-Galvez, M.; Sanchez-Villalobos, J. M.; Achel, D. G.; Olmos, E.; Martinez-Hernandez, C. M.

2012-01-01

Thirty for (34) published studies, conducted from 1994 to the present to evaluate the genotoxic effect of magnetic fields using ELF-EMF and diagnostic resonance on humans by the micronucleus assay have been reviewed. some characteristics of the assay methods, their significance to genotoxicity and basic interpretations of the results of these assays are discussed. of the studies analysed 70.5% implicated genotoxic effects induced by these magnetic fields: 52.9% were due to exposure to magnetic fields only and 17,6% by exposure to magnetic fields in combination with some treatment types, resulting in additive or synergistic effect. Evidence exist to support the notion that exposure of humans to magnetic fields stimulates genotoxic effects, although the actual mechanisms of action or even the true human health consequences resulting from these exposure still remain unclear. (Author) 80 refs.

Soil genotoxicity assessment: a new stategy based on biomolecular tools and plant bioindicators.

Science.gov (United States)

Citterio, Sandra; Aina, Roberta; Labra, Massimo; Ghiani, Alessandra; Fumagalli, Pietro; Sgorbati, Sergio; Santagostino, Angela

2002-06-15

The setting up of efficient early warning systems is a challenge to research for preventing environmental alteration and human disease. In this paper, we report the development and the field application of a new biomonitoring methodology for assessing soil genotoxicity. In the first part, the use of amplified fragment length polymorphism and flow cytometry techniques to detect DNA damage induced by soils artificially contaminated with heavy metals as potentially genotoxic compounds is explained. Results show that the combination of the two techniques leads to efficient detection of the sublethal genotoxic effect induced in the plant bioindicator by contaminated soil. By contrast, the classic mortality, root, and shoot growth vegetative endpoints prove inappropriate for assessing soil genotoxicity because, although they cause genotoxic damage, some heavy metals do not affect sentinel plant development negatively. The statistical elaboration of the data obtained led to the development of a statistical predictive model which differentiates four different levels of soil genotoxic pollution and can be used everywhere. The second part deals with the application of the biomonitoring protocol in the genotoxic assessment of two areas surrounding a steelworks in northern Italy and the effectiveness of this methodology. In this particular case, in these areas, the predictive model reveals a pollution level strictly correlated to the heavy metal concentrations revealed by traditional chemical analysis.

Environmental drivers of variability in the movement ecology of turkey vultures (Cathartes aura) in North and South America.

Science.gov (United States)

Dodge, Somayeh; Bohrer, Gil; Bildstein, Keith; Davidson, Sarah C; Weinzierl, Rolf; Bechard, Marc J; Barber, David; Kays, Roland; Brandes, David; Han, Jiawei; Wikelski, Martin

2014-01-01

Variation is key to the adaptability of species and their ability to survive changes to the Earth's climate and habitats. Plasticity in movement strategies allows a species to better track spatial dynamics of habitat quality. We describe the mechanisms that shape the movement of a long-distance migrant bird (turkey vulture, Cathartes aura) across two continents using satellite tracking coupled with remote-sensing science. Using nearly 10 years of data from 24 satellite-tracked vultures in four distinct populations, we describe an enormous amount of variation in their movement patterns. We related vulture movement to environmental conditions and found important correlations explaining how far they need to move to find food (indexed by the Normalized Difference Vegetation Index) and how fast they can move based on the prevalence of thermals and temperature. We conclude that the extensive variability in the movement ecology of turkey vultures, facilitated by their energetically efficient thermal soaring, suggests that this species is likely to do well across periods of modest climate change. The large scale and sample sizes needed for such analysis in a widespread migrant emphasizes the need for integrated and collaborative efforts to obtain tracking data and for policies, tools and open datasets to encourage such collaborations and data sharing.

Borax counteracts genotoxicity of aluminum in rat liver.

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Turkez, Hasan; Geyikoğlu, Fatime; Tatar, Abdulgani

2013-10-01

This study was carried out to evaluate the protective role of borax (BX) on genotoxicity induced by aluminum (Al) in rat liver, using liver micronucleus assay as an indicator of genotoxicity. Sprague-Dawley rats were randomly separated into six groups and each group had four animals. Aluminum chloride (AlCl₃; 5 mg/kg b.w.) and BX (3.25 and 13 mg/kg b.w.) were injected intraperitoneally to rats. Besides, animals were also treated with Al for 4 consecutive days followed by BX for 10 days. Rats were anesthetized after Al and BX injections and the hepatocytes were isolated for counting the number of micronucleated hepatocytes (MNHEPs). AlCl₃ was found to significantly (p < 0.05) increase the number of MNHEPs. Rats treated with BX, however, showed no increase in MNHEPs. Moreover, simultaneous treatments with BX significantly modulated the genotoxic effects of AlCl₃ in rats. It can be concluded that BX has beneficial influences and has the ability to antagonize Al toxicity.

Genotoxicity evaluation of the insecticide ethion in root of Allium ...

African Journals Online (AJOL)

USER

2010-07-05

Jul 5, 2010 ... In this study, the genotoxic effects of ethion were investigated in the mitotic cell division of Allium ... The use of plant root tips, particularly those of A. cepa and Vicia faba, as a bioassay test system for the genotoxicity of pesticides has shown extremely ..... the long run, even below the recommended dose.

Genotoxicity test of irradiated foods

International Nuclear Information System (INIS)

Tanaka, Noriho

2004-01-01

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

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

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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.

A whole-cell bioreporter assay for quantitative genotoxicity evaluation of environmental samples.

Science.gov (United States)

Jiang, Bo; Li, Guanghe; Xing, Yi; Zhang, Dayi; Jia, Jianli; Cui, Zhisong; Luan, Xiao; Tang, Hui

2017-10-01

Whole-cell bioreporters have emerged as promising tools for genotoxicity evaluation, due to their rapidity, cost-effectiveness, sensitivity and selectivity. In this study, a method for detecting genotoxicity in environmental samples was developed using the bioluminescent whole-cell bioreporter Escherichia coli recA::luxCDABE. To further test its performance in a real world scenario, the E. coli bioreporter was applied in two cases: i) soil samples collected from chromium(VI) contaminated sites; ii) crude oil contaminated seawater collected after the Jiaozhou Bay oil spill which occurred in 2013. The chromium(VI) contaminated soils were pretreated by water extraction, and directly exposed to the bioreporter in two phases: aqueous soil extraction (water phase) and soil supernatant (solid phase). The results indicated that both extractable and soil particle fixed chromium(VI) were bioavailable to the bioreporter, and the solid-phase contact bioreporter assay provided a more precise evaluation of soil genotoxicity. For crude oil contaminated seawater, the response of the bioreporter clearly illustrated the spatial and time change in genotoxicity surrounding the spill site, suggesting that the crude oil degradation process decreased the genotoxic risk to ecosystem. In addition, the performance of the bioreporter was simulated by a modified cross-regulation gene expression model, which quantitatively described the DNA damage response of the E. coli bioreporter. Accordingly, the bioluminescent response of the bioreporter was calculated as the mitomycin C equivalent, enabling quantitative comparison of genotoxicities between different environmental samples. This bioreporter assay provides a rapid and sensitive screening tool for direct genotoxicity assessment of environmental samples. Copyright © 2017. Published by Elsevier Ltd.

Mutagenicity and genotoxicity of coal fly ash water leachate.

Science.gov (United States)

Chakraborty, Rajarshi; Mukherjee, Anita

2009-03-01

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 significant (Ppercentage (%), tail length (mum), 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.

Evaluation of Genotoxic Pressure along the Sava River.

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Stoimir Kolarević

Full Text Available 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.

Plant genotoxicity: a molecular cytogenetic approach in plant bioassays.

Science.gov (United States)

Maluszynska, Jolanta; Juchimiuk, Jolanta

2005-06-01

It is important for the prevention of DNA changes caused by environment to understand the biological consequences of DNA damages and their molecular modes of action that lead to repair or alterations of the genetic material. Numerous genotoxicity assay systems have been developed to identify DNA reactive compounds. The available data show that plant bioassays are important tests in the detection of genotoxic contamination in the environment and the establishment of controlling systems. Plant system can detect a wide range of genetic damage, including gene mutations and chromosome aberrations. Recently introduced molecular cytogenetic methods allow analysis of genotoxicity, both at the chromosomal and DNA level. FISH gives a new possibility of the detection and analysis of chromosomal rearrangements in a great detail. DNA fragmentation can be estimated using the TUNEL test and the single cell gel electrophoresis (Comet assay).

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.

Evaluation of Cytotoxicity and Genotoxicity of Acacia aroma Leaf Extracts

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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.

Genotoxicity of drinking water treated with different disinfectants and effects of disinfection conditions detected by umu-test.

Science.gov (United States)

Nie, Xuebiao; Liu, Wenjun; Zhang, Liping; Liu, Qing

2017-06-01

The genotoxicity of drinking water treated with 6 disinfection methods and the effects of disinfection conditions were investigated using the umu-test. The pretreatment procedure of samples for the umu-test was optimized for drinking water analysis. The results of the umu-test were in good correlation with those of the Ames-test. The genotoxicity and production of haloacetic acids (HAAs) were the highest for chlorinated samples. UV+chloramination is the safest disinfection method from the aspects of genotoxicity, HAA production and inactivation effects. For chloramination, the effects of the mass ratio of Cl 2 to N of chloramine on genotoxicity were also studied. The changes of genotoxicity were different from those of HAA production, which implied that HAA production cannot represent the genotoxic potential of water. The genotoxicity per chlorine decay of chlorination and chloramination had similar trends, indicating that the reaction of organic matters and chlorine made a great contribution to the genotoxicity. The results of this study are of engineering significance for optimizing the operation of waterworks. Copyright © 2016. Published by Elsevier B.V.

Somatic cell genotoxicity at the glycophorin A locus in humans

International Nuclear Information System (INIS)

Jensen, R.H.; Grant, S.G.; Langlois, R.G.; Bigbee, W.L.

1990-01-01

We have developed an assay for detecting variant erythrocytes that occur as a result of in vivo allele loss at the glycophorin A (GPA) locus on chromosome 4 in humans. This gene codes for an erythroid- specific cell surface glycoprotein, and with our assay we are able to detect rare variant erythrocytes that have lost expression of one of the two GPA alleles. Two distinctly different variant cell types are detected with this assay. One variant cell type (called N OE) is hemizygous. Our assay also detects homozygous variant erythrocytes that have lost expression of the GPA(M) allele and express the GPA(N) allele at twice the heterozygous level. The results of this assay are an enumeration of the frequency of N OE and NN variant cell types for each individual analyzed. These variant cell frequencies provide a measure of the amount of somatic cell genotoxicity that has occurred at the GPA locus. Such genotoxicity could be the result of (1) reactions of toxic chemicals to which the individual has been exposed, or (2) high energy radiation effects on erythroid precursor cells, or (3) errors in DNA replication or repair in these cells of the bone marrow. Thus, the GPA-based variant cell frequency can serve as a biodosimeter that indicates the amount of genotoxic exposure each individual has received. Because two very different kinds of variant cells are enumerated, different kinds of genotoxicity should be distinguishable. Results of the GPA somatic genotoxicity assay may also provide valuable information for cancer-risk estimation on each individual. 16 refs

Genistein genotoxicity: Critical considerations of in vitro exposure dose

International Nuclear Information System (INIS)

Klein, Catherine B.; King, Audrey A.

2007-01-01

The potential health benefits of soy-derived phytoestrogens include their reported utility as anticarcinogens, cardioprotectants and as hormone replacement alternatives in menopause. Although there is increasing popularity of dietary phytoestrogen supplementation and of vegetarian and vegan diets among adolescents and adults, concerns about potential detrimental or other genotoxic effects persist. While a variety of genotoxic effects of phytoestrogens have been reported in vitro, the concentrations at which such effects occurred were often much higher than the physiologically relevant doses achievable by dietary or pharmacologic intake of soy foods or supplements. This review focuses on in vitro studies of the most abundant soy phytoestrogen, genistein, critically examining dose as a crucial determinant of cellular effects. In consideration of levels of dietary genistein uptake and bioavailability we have defined in vitro concentrations of genistein > 5 μM as non-physiological, and thus 'high' doses, in contrast to much of the previous literature. In doing so, many of the often-cited genotoxic effects of genistein, including apoptosis, cell growth inhibition, topoisomerase inhibition and others become less obvious. Recent cellular, epigenetic and microarray studies are beginning to decipher genistein effects that occur at dietarily relevant low concentrations. In toxicology, the well accepted principle of 'the dose defines the poison' applies to many toxicants and can be invoked, as herein, to distinguish genotoxic versus potentially beneficial in vitro effects of natural dietary products such as genistein

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

Cytotoxicity and genotoxicity of biogenic silver nanoparticles

International Nuclear Information System (INIS)

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

2013-01-01

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.

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

Science.gov (United States)

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

2008-09-17

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

In vitro and in vivo genotoxic evaluation of Bothrops moojeni snake venom.

Science.gov (United States)

Novak Zobiole, Nathalia; Caon, Thiago; Wildgrube Bertol, Jéssica; Pereira, Cintia Alves de Souza; Okubo, Brunna Mary; Moreno, Susana Elisa; Cardozo, Francielle Tramontini Gomes de Sousa

2015-06-01

Bothrops moojeni Hoge (Viperidae) venom is a complex mixture of compounds with therapeutic potential that has been included in the research and development of new drugs. Along with the biological activity, the pharmaceutical applicability of this venom depends on its toxicological profile. This study evaluates the cytotoxicity and genotoxicity of the Bothrops moojeni venom (BMV). The in vitro cytotoxicity and genotoxicity of a pooled sample of BMV was assessed by the MTT and Comet assay, respectively. Genotoxicity was also evaluated in vivo through the micronucleus assay. BMV displayed a 50% cytotoxic concentration (CC50) on Vero cells of 4.09 µg/mL. Vero cells treated with 4 µg/mL for 90 min and 6 h presented significant (p < 0.05, ANOVA/Newman-Keuls test) higher DNA damage than the negative control in the Comet assay. The lower DNA damage found after 6 h compared with the 90 min treatment suggests a DNA repair effect. Mice intraperitoneally treated with BMV at 10, 30, or 80 µg/animal presented significant genotoxicity (p < 0.05, ANOVA/Newman-Keuls test) in relation to the negative control after 24 h of treatment. Contrary to the in vitro results, no DNA repair seemed to occur in vivo up to 96 h post-venom inoculation at a dose of 30 µg/animal. The results show that BMV presents cyto- and genotoxicity depending on the concentration/dose used. These findings emphasize the importance of toxicological studies, including assessment of genotoxicity, in the biological activity research of BMV and/or in the development of BMV-derived products.

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.

Considerations on photochemical genotoxicity. II: Report of the 2009 International Workshop on Genotoxicity Testing Working Group

NARCIS (Netherlands)

Lynch, A.M.; Guzzie, P.J.; Bauer, D.; Gocke, E.; Itoh, S.; Jacobs, A.; Krul, C.A.M.; Schepky, A.; Tanaka, N.; Kasper, P.

2011-01-01

A workshop to reappraise the previous IWGT recommendations for photogenotoxicity testing [E. Gocke, L. Muller, P.J. Guzzie, S. Brendler-Schwaab, S. Bulera, C.F. Chignell, L.M. Henderson, A. Jacobs, H. Murli, R.D. Snyder, N. Tanaka, Considerations on photochemical genotoxicity: report of the

AFFINITY BIOSENSOR BASED ON SCREEN-PRINTED ELECTRODE MODIFIED WITH DNA FOR GENOTOXIC COMPOUNDS DETECTION

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Bambang Kuswandi

2010-06-01

Full Text Available An electrochemical method for the detection of the genotoxic compounds using a DNA-modified electrode was developed. This electrode was successfully used for the electrochemical detection of genotoxic compounds in water samples. The electrochemical results clearly demonstrated that, the development is related to the molecular interaction between the surface-linked DNA obtained from calf thymus and the target compounds, such as pollutants, in order to develop a simple device for rapid screening of genotoxic compounds in environmental samples. The detection of such compounds was measured by their effect on the oxidation signal of the guanine peak of the DNA immobilised on the surface of carbon based Screen-Printed Electrode (SPE in disposable mode, and monitored by square-wave voltametric analysis. The DNA biosensor is able to detect known intercalating and groove-binding genotoxic compounds such as Dioxin, Bisphenol A, PCBs, and Phtalates. Application to real water samples is discussed and reported.   Keywords: electrochemical, screen-printed electrode, DNA biosensor, genotoxic compounds

Genotoxic Maillard byproducts in current phytopharmaceutical preparations of Echinodorus grandiflorus

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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.

Correlation between serum anyloid a low density lipoprotein and genotoxicity in smokers

International Nuclear Information System (INIS)

Jamil, A.; Rashid, A.; Majeed, A.; Naveed, A.K.

2018-01-01

Objective:To investigate the relation between serum amyloid A-low density lipoprotein (SAA-LDL) and genotoxicity in smokers. Study Design:An experimental study. Place and Duration of Study:Army Medical College, Rawalpindi and National Institute of Health (NIH), Islamabad, from June 2014 to February 2015. Methodology:Seventy healthy Sprague Dawley rats were purchased from NIH and exposed to cigarette smoke in smoke chamber for three months. Blood samples were drawn from each rat at the end of the study period. SAA-LDL was determined by enzyme-linked immunosorbent assay (ELISA). Genotoxicity was assessed by cytokinesis block micronucleus (CBMN) assay. Pearson correlation was used to find correlation between SAA-LDL and genotoxicity. Results:Strong positive correlation was found between SAA-LDL and micronuclei frequency in smoke-exposed rats (r=0.799, N=70, p <0.01). Conclusion:Statistically significant strong positive correlation between SAA-LDL and genotoxicity in smoke-exposed rats shows that changes in one is associated with changes in other and vice versa. (author)

Evaluation of perfluorooctanoate for potential genotoxicity

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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

Evaluation of genotoxicity of nitrile fragrance ingredients using in vitro and in vivo assays.

Science.gov (United States)

Bhatia, S P; Politano, V T; Api, A M

2013-09-01

Genotoxicity studies were conducted on a group of 8 fragrance ingredients that belong to the nitrile family. These nitriles are widely used in consumer products however there is very limited data in the literature regarding the genotoxicity of these nitriles. The 8 nitriles were assessed for genotoxicity using an Ames test, in vitro chromosome aberration test or in vitro micronucleus test. The positive results observed in the in vitro tests were further investigated using an in vivo micronucleus test. The results from these different tests were compared and these 8 nitriles are not considered to be genotoxic. Dodecanitrile and 2,2,3-trimethylcyclopent-3-enylacetonitrile were negative in the in vitro chromosome aberration test and in vitro micronucleus test, respectively. While citronellyl nitrile, 3-methyl-5-phenylpentanenitrile, cinnamyl nitrile, and 3-methyl-5-phenylpent-2-enenitrile revealed positive results in the in vitro tests, but confirmatory in vivo tests determined these nitriles to be negative in the in vivo micronucleus assay. The remaining two nitriles (benzonitrile and α-cyclohexylidene benzeneacetonitrile) were negative in the in vivo micronucleus test. This study aims to evaluate the genotoxicity potential of these nitriles as well as enrich the literature with genotoxicity data on fragrance ingredients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cytotoxicity and genotoxicity of clothianidin in human lymphocytes with or without metabolic activation system.

Science.gov (United States)

Atlı Şekeroğlu, Zülal; Şekeroğlu, Vedat; Uçgun, Ebru; Kontaş Yedier, Seval; Aydın, Birsen

2018-02-26

Clothianidin (CHN) is a broad-spectrum neonicotinoid insecticide. Limited studies have been carried out on the cytotoxic and genotoxic effects of both CHN using different genotoxicity tests in human cells with or without human metabolic activation system (S9 mix). Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of CHN and its metabolites on human lymphocyte cultures with or without S9 mix using chromosomal aberration (CA) and micronucleus (MN) tests. The cultures were treated with 25, 50, and 100 µg/ml of CHN in the presence (3 h treatment) and absence (48 h treatment) of S9 mix. Dimethyl sulfoxide (DMSO) was used as a solvent control. CHN showed cytotoxic and genotoxic effects due to significant decreases in mitotic index (MI) and nuclear division index (NDI), and significant increases in the CAs, aberrant cells, and MN formation in the absence of S9 mix when compared with solvent control. However, CHN did not significantly induce cytotoxicity and genotoxicity in the presence of S9 mix. Our results indicated that CHN has cytotoxic, cytostatic, and genotoxic potential on human peripheral blood lymphocyte cultures, but not its metabolites under the experimental conditions.

Molecular and cytogenetic assessment of Dipterygium glaucum genotoxicity

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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

Genotoxicity of antiobesity drug orlistat and effect of caffeine intervention: an in vitro study.

Science.gov (United States)

Chakrabarti, Manoswini; Ghosh, Ilika; Jana, Aditi; Ghosh, Manosij; Mukherjee, Anita

2017-07-01

Obesity is a major global health problem associated with various adverse effects. Pharmacological interventions are often necessary for the management of obesity. Orlistat is an FDA-approved antiobesity drug which is a potent inhibitor of intestinal lipases. In the current study, orlistat was evaluated for its genotoxic potential in human lymphocyte cells in vitro and was compared with that of another antiobesity drug sibutramine, presently withdrawn from market due its undesirable health effects. Caffeine intake may be an additional burden in people using anorectic drugs, therefore, further work is needed to be carried out to evaluate the possible effects of caffeine on orlistat-induced DNA damage. Human lymphocytes were exposed to orlistat (250, 500 and 1000 μg/ml), sibutramine (250, 500 and 1000 μg/ml) and caffeine (25, 50, 75, 100, 125 and 150 μg/ml) to assess their genotoxicity by comet assay in vitro. In addition, lymphocytes were co-incubated with caffeine (50, 75 and 100 μg/ml) and a single concentration of orlistat (250 μg/ml). Orlistat and sibutramine were genotoxic at all concentrations tested, sibutramine being more genotoxic. Caffeine was found to be genotoxic at concentrations 125 μg/ml and above. Co-treatment of orlistat with non-genotoxic concentrations (50, 75 and 100 μg/ml) of caffeine lead to a decrease in DNA damage. Orlistat can induce DNA damage in human lymphocytes in vitro and caffeine was found to reduce orlistat-induced genotoxicity.

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.

Comparative Physicochemical and Genotoxicity Assessments of ...

African Journals Online (AJOL)

ADOWIE PERE

ABSTRACT: The textile industry has become indispensable in view of its basic and social importance to human life, but its environmental impact has continued to be a subject of concern. ... the economy of many countries. ... Textile and clothing production process ..... Genotoxicity screening of industrial effluents using.

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......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...... in crude suspensions (suspended in cell culture medium) and crude suspensions filtrated through a 0.2 µm pore size filter in order to investigate the potential effect of “nanoparticles” only. The two clays showed noticeable differences in genotoxicity; both crude and filtered suspensions of Cloisite...

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

Science.gov (United States)

Gülsoy, Nagihan; Yavas, 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 Olive tail moment. Genotoxicity was found for BA as concentration-dependent and BX as concentration and time dependent manner. In general, significant effects (P borax-induced genotoxicity in fish.

Genotoxic Effects of Exposure to Gasoline Fumes on Petrol Pump Workers

OpenAIRE

Amrin Shaikh; Darshana Barot; Divya Chandel

2018-01-01

Background: Petrol pump workers are occupationally exposed to gasoline and its fumes consisting of several mutagenic chemicals. Objective: To evaluate the genotoxic effects of exposure to gasoline fumes on petrol pump workers. Methods: The study groups included 70 petrol pump workers (exposed group) and 70 healthy age-matched individuals with no known exposure (comparison group). Buccal micronucleus cytome assay (BMCyt) was performed to check the genotoxicity caused due to inhalation ...

DNA adduct profiling of in vitro colonic meat digests to map red vs. white meat genotoxicity.

Science.gov (United States)

Hemeryck, Lieselot Y; Rombouts, Caroline; De Paepe, Ellen; Vanhaecke, Lynn

2018-05-01

The consumption of red meat has been linked to an increased colorectal cancer (CRC) risk. One of the major hypotheses states that heme iron (present in red meat) stimulates the formation of genotoxic N-nitroso compounds (NOCs) and lipid peroxidation products (LPOs). By means of DNA adductomics, chemically induced DNA adduct formation can be mapped in relation to e.g. dietary exposures. In this study, this state-of-the-art methodology was used to investigate alkylation and (lipid per)oxidation induced DNA adduct formation in in vitro red vs. white meat digests. In doing so, 90 alkylation and (lipid per)oxidation induced DNA adduct types could be (tentatively) identified. Overall, 12 NOC- and/or LPO-related DNA adduct types, i.e. dimethyl-T (or ethyl-T), hydroxymethyl-T, tetramethyl-T, methylguanine (MeG), guanidinohydantoin, hydroxybutyl-C, hydroxymethylhydantoin, malondialdehyde-x3-C, O 6 -carboxymethylguanine, hydroxyethyl-T, carboxyethyl-T and 3,N 4 -etheno-C were singled out as potential heme-rich meat digestion markers. The retrieval of these DNA adduct markers is in support of the heme, NOC and LPO hypotheses, suggesting that DNA adduct formation may indeed contribute to red meat related CRC risk. Copyright © 2018 Elsevier Ltd. All rights reserved.

Genotoxicity assessment of some cosmetic and food additives.

Science.gov (United States)

Di Sotto, Antonella; Maffei, Francesca; Hrelia, Patrizia; Di Giacomo, Silvia; Pagano, Ester; Borrelli, Francesca; Mazzanti, Gabriela

2014-02-01

α-Hexylcinnamaldehyde (HCA) and p-tert-butyl-alpha-methylhydrocinnamic aldehyde (BMHCA) are synthetic aldehydes, characterized by a typical floral scent, which makes them suitable to be used as fragrances in personal care (perfumes, creams, shampoos, etc.) and household products, and as flavouring additives in food and pharmaceutical industry. The aldehydic structure suggests the need for a safety assessment for these compounds. Here, HCA and BMHCA were evaluated for their potential genotoxic risk, both at gene level (frameshift or base-substitution mutations) by the bacterial reverse mutation assay (Ames test), and at chromosomal level (clastogenicity and aneuploidy) by the micronucleus test. In order to evaluate a primary and repairable DNA damage, the comet assay has been also included. In spite of their potential hazardous chemical structure, a lack of mutagenicity was observed for both compounds in all bacterial strains tested, also in presence of the exogenous metabolic activator, showing that no genotoxic derivatives were produced by CYP450-mediated biotransformations. Neither genotoxicity at chromosomal level (i.e. clastogenicity or aneuploidy) nor single-strand breaks were observed. These findings will be useful in further assessing the safety of HCA and BMHCA as either flavour or fragrance chemicals. Copyright © 2013 Elsevier Inc. All rights reserved.

Colon cancer

Science.gov (United States)

Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma; Colon carcinoma ... eat may play a role in getting colon cancer. Colon cancer may be linked to a high-fat, ...

Evaluation of the tickcide, genotoxic, and mutagenic effects of the Ruta graveolens L. (Rutaceae

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Alessandra Vargas de Carvalho

2015-10-01

Full Text Available Current analysis investigated the tickcide effects of the aqueous extract and chloroform fractions of Ruta graveolens L. (rue on engorged females of Rhipicephalus microplus, as well as their genotoxic and mutagenic effects on human leukocytes. The best tickcide activity (non-dependent dose and genotoxic / mutagenic effects (dependent-dose were observed on exposure to chloroform fractions. Results suggest that extract fractions of R. graveolens L are efficient against R. microplus, although the fraction and the tested concentrations show genotoxic and mutagenic potential for human leukocytes.

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.

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

International Nuclear Information System (INIS)

Villarini, M.; Fatigoni, C.; Dominici, L.; Maestri, S.; Ederli, L.; Pasqualini, S.; Monarca, S.; Moretti, M.

2009-01-01

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.

Genotoxicity Screening of Industrial Effluents using Onion bulbs ...

African Journals Online (AJOL)

Michael Horsfall

ABSTRACT: The potential cytotoxicity and genotoxicity of three industrial wastewaters (brewery .... National recommended water quality criteria – correction; cWorld Health Organisation (1996). ..... Industrial Pollution Policy Management Study.

Toward a Genotoxic Protection Factor

International Nuclear Information System (INIS)

Cesarini, J.P.; Demanneville, S.

2000-01-01

P53, a molecule normally expressed before mitosis, is considered as the 'guardian of the genome'. In the skin its level is normally very low (<3% of cells), detected by immunohistochemical methods. At least 50% of the keratinocytes express p53 protein, 24 h following a significant UV irradiation (2 SED). It is expected using sunscreens to reduce the expression of p53 in parallel with their ability to reduce the actinic erythema, the endpoint adopted to evaluate the Sun Protection Factor (SPF) of sunscreens. P53 detection on biopsies performed on the buttocks of human volunteers was used to evaluate the genotoxic protecting factor (GPF) of several sunscreens with either high UVB filtration or high UVA filtration, characterised by various SPF (COLIPA) from 10 to 40. The p53 count in parallel with sunburn cell count were the parameters studied. In general, the GPF of the sunscreens was found below the proprietary SPF. If a genotoxic effect is shown in an increased p53 expression, this effect is still observed at a dose lower than the dose inducing the faintest actinic erythema. (author)

Toward a Genotoxic Protection Factor

Energy Technology Data Exchange (ETDEWEB)

Cesarini, J.P.; Demanneville, S

2000-07-01

P53, a molecule normally expressed before mitosis, is considered as the 'guardian of the genome'. In the skin its level is normally very low (<3% of cells), detected by immunohistochemical methods. At least 50% of the keratinocytes express p53 protein, 24 h following a significant UV irradiation (2 SED). It is expected using sunscreens to reduce the expression of p53 in parallel with their ability to reduce the actinic erythema, the endpoint adopted to evaluate the Sun Protection Factor (SPF) of sunscreens. P53 detection on biopsies performed on the buttocks of human volunteers was used to evaluate the genotoxic protecting factor (GPF) of several sunscreens with either high UVB filtration or high UVA filtration, characterised by various SPF (COLIPA) from 10 to 40. The p53 count in parallel with sunburn cell count were the parameters studied. In general, the GPF of the sunscreens was found below the proprietary SPF. If a genotoxic effect is shown in an increased p53 expression, this effect is still observed at a dose lower than the dose inducing the faintest actinic erythema. (author)

Genotoxicity tests on D-tagatose.

Science.gov (United States)

Kruger, C L; Whittaker, M H; Frankos, V H

1999-04-01

D-tagatose is a low-calorie sweetener that tastes like sucrose. Its genotoxic potential was examined in five standard assays: the Ames Salmonella typhimurium reverse mutation assay, the Escherichia coli/mammalian microsome assay, a chromosomal aberration assay in Chinese hamster ovary cells, a mouse lymphoma forward mutation assay, and an in vivo mouse micronucleus assay. D-tagatose was not found to increase the number of revertants per plate relative to vehicle controls in either the S. typhimurium tester strains or the WP2uvrA- tester strain with or without metabolic activation at doses up to 5000 microg/plate. No significant increase in Chinese hamster ovary cells with chromosomal aberrations was observed at concentrations up to 5000 microg/ml with or without metabolic activation. D-tagatose was not found to increase the mutant frequency in mouse lymphoma L5178Y cells with or without metabolic activation up to concentrations of 5000 microg/ml. D-tagatose caused no significant increase in micronuclei in bone marrow polychromatic erythrocytes at doses up to 5000 mg/kg. D-tagatose was not found to be genotoxic under the conditions of any of the assays described above. Copyright 1999 Academic Press.

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

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.

Genotoxicity of unmodified and organo-modified montmorillonite

DEFF Research Database (Denmark)

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

2010-01-01

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...... assay, none of the clays produced ROS in a cell-free test system (the DCFH-DA assay). Inductively coupled plasma mass-spectrometry (ICP-MS) was used to detect clay particles in the filtered samples using aluminium as a tracer element characteristic to clay. The results indicated that clay particles were...... 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...

Genotoxicity Biomonitoring Along a Coastal Zone Under Influence of Offshore Petroleum Exploration (Southeastern Brazil).

Science.gov (United States)

Gutiérrez, Juan Manuel; da Conceição, Moisés Basilio; Molisani, Mauricio Mussi; Weber, Laura Isabel

2018-03-01

Offshore oil exploration creates threats to coastal ecosystems, including increasing urbanization and associated effluent releases. Genotoxicity biomarkers in mussels were determined across a gradient of coastal zone influences of offshore petroleum exploration in southeastern Brazil. Coastal ecosystems such as estuaries, beaches and islands were seasonally monitored for genotoxicity evaluation using the brown mussel Perna perna. The greatest DNA damage (5.2% ± 1.9% tail DNA and 1.5‰  ± 0.8‰ MN) were observed in urban estuaries, while Santana Archipelago showed levels of genotoxicity near zero and is considered a reference site. Mussels from urban and pristine beaches showed intermediate damage levels, but were also influenced by urbanization. Thus, mussel genotoxicity biomarkers greatly indicated the proposed oil exploration and urbanization scenarios that consequently are genetically affecting coastal organisms.

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...

Primary genotoxicity in the liver following pulmonary exposure to carbon black nanoparticles in mice

DEFF Research Database (Denmark)

Modrzynska, Justyna; Berthing, Trine; Ravn-Haren, Gitte

2018-01-01

Background Little is known about the mechanism underlying the genotoxicity observed in the liver following pulmonary exposure to carbon black (CB) nanoparticles (NPs). The genotoxicity could be caused by the presence of translocated particles or by circulating inflammatory mediators released during...

Proteome-wide Identification of Poly(ADP-Ribosyl)ation Targets in Different Genotoxic Stress Responses

DEFF Research Database (Denmark)

Jungmichel, S.; Rosenthal, F.; Altmeyer, M.

2013-01-01

. Nuclear proteins encompassing nucleic acid binding properties are prominently PARylated upon genotoxic stress, consistent with the nuclear localization of ARTD1/PARP1 and ARTD2/PARP2. Distinct differences in proteins becoming PARylated upon various genotoxic insults are observed, exemplified...

A novel mechanism of oxidative genotoxicity

Indian Academy of Sciences (India)

The genotoxicity of reactive oxygen species (ROS) is well established. The underlying mechanism involves oxidation of DNA by ROS. However, we have recently shown that hydrogen peroxide (H2O2), the major mediator of oxidative stress, can also cause genomic damage indirectly. Thus, H2O2 at pathologically relevant ...

Assessing genotoxic effects in fish from a marine protected area influenced by former mining activities and other stressors

International Nuclear Information System (INIS)

Gusso-Choueri, Paloma Kachel; Choueri, Rodrigo Brasil; Santos, Gustavo Souza; Seraphim de Araújo, Giuliana; Feitosa Cruz, Ana Carolina

2016-01-01

The goal of the current study was to evaluate different genotoxicity tools in order to assess a marine protected area (MPA) affected by former mining activities and urban settlements. A catfish (Cathorops spixii) was analyzed for genotoxic effects at the (i) molecular and at the (ii) chromosomal levels. Through factor analysis, genotoxicity was found to be linked to levels of metals bioaccumulated and PAH metabolites in the bile. Micronucleus and nuclear alteration were less vulnerable to the effects of confounding factors in mildly contaminated areas since they were more frequently associated with bioaccumulated metals than the DNA analysis. The different genotoxicity responses allowed for the identification of sources of pollution in the MPA. This approach was important for detecting environmental risks related to genotoxic contaminants in a mildly contaminated MPA. -- Highlights: •We assessed genotoxicity and bioaccumulation in catfish from a marine protected area. •The area is under the influence of past mining activities and urban settlements. •Cellular level responses were highly associated with body burdens of metals and As. •Responses at the molecular level were less associated with body burdens. •Genotoxicity in different organs helped identify pollution sources in MPA.

Impacts of fullerene C60 and virgin olive oil on cadmium-induced genotoxicity in rats.

Science.gov (United States)

Aly, Fayza M; Kotb, Ahmed M; Haridy, Mohie A M; Hammad, Seddik

2018-07-15

Currently, cadmium is considered to be one of the major environmental pollutants. Environmentally, cadmium is released in various forms e.g. oxide, chloride and sulphide. The aim of the present study was to examine the genotoxic impact of fullerene nanoparticles C 60 (C 60 ) and virgin olive oil (VOO) on cadmium chloride (CdCl 2 )-induced genotoxicity in rats. To evaluate these effects on DNA damage and chromosomal frequency, 25 albino rats were randomly assigned to 5 groups (n=5 per group): Group 1 served as a control; Group 2 received a single intraperitoneal dose of CdCl 2 (3.5mg/kg); Group 3 animals were treated with C 60 (4mg/kg, orally) every other day for 20days; Group 4 received a single intraperitoneal dose of CdCl 2 (3.5mg/kg) and an oral dose of C 60 (4mg/kg); and Group 5 received a single intraperitoneal dose of CdCl 2 (3.5mg/kg) and oral doses of VOO every other day for 20 consecutive days. Genotoxic and anti-genotoxic effects of C 60 and VOO were evaluated in the liver, kidney and bone marrow using molecular and cytogenetic assays. As expected, CdCl 2 and C 60 administration was associated with band number alterations in both liver and kidney; however, C 60 pretreatment recovered to approximately basal number. Surprisingly, C 60 and VOO significantly attenuated the genotoxic effects caused by CdCl 2 in livers and kidneys. In bone marrow, in addition to a reduction in the chromosomal number, several chromosomal aberrations were caused by CdCl 2 . These chromosomal alterations were also reversed by C 60 and VOO. In conclusion, molecular and cytogenetic studies showed that C 60 and VOO exhibit anti-genotoxic agents against CdCl 2 -induced genotoxicity in rats. Further studies are needed to investigate the optimal conditions for potential biomedical applications of these anti-genotoxic agents. Copyright © 2018 Elsevier B.V. All rights reserved.

Tungsten carbide-cobalt as a nanoparticulate reference positive control in in vitro genotoxicity assays.

Science.gov (United States)

Moche, Hélène; Chevalier, Dany; Barois, Nicolas; Lorge, Elisabeth; Claude, Nancy; Nesslany, Fabrice

2014-01-01

With the increasing human exposure to nanoparticles (NP), the evaluation of their genotoxic potential is of significant importance. However, relevance for NP of the routinely used in vitro genotoxicity assays is often questioned, and a nanoparticulate reference positive control would therefore constitute an important step to a better testing of NP, ensuring that test systems are really appropriate. In this study, we investigated the possibility of using tungsten carbide-cobalt (WC-Co) NP as reference positive control in in vitro genotoxicity assays, including 2 regulatory assays, the mouse lymphoma assay and the micronucleus assay, and in the Comet assay, recommended for the toxicological evaluation of nanomedicines by the French Agency of Human Health Products (Afssaps). Through these assays, we were able to study different genetic endpoints in 2 cell types commonly used in regulatory genotoxicity assays: the L5178Y mouse lymphoma cell line and primary cultures of human lymphocytes. Our results showed that the use of WC-Co NP as positive control in in vitro genotoxicity assays was conceivable, but that different parameters have to be considered, such as cell type and treatment schedule. L5178Y mouse lymphoma cells did not provide satisfactory results in the 3 performed tests. However, human lymphocytes were more sensitive to genotoxic effects induced by WC-Co NP, particularly after a 24-h treatment in the in vitro micronucleus assay and after a 4-h treatment in the in vitro Comet assay. Under such conditions, WC-Co could be used as a nanoparticulate reference positive control in these assays.

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. Copyright © 2015

Genotoxic evaluation of an industrial effluent from an oil refinery using plant and animal bioassays.

Science.gov (United States)

Rodrigues, Fernando Postalli; Angeli, José Pedro Friedmann; Mantovani, Mário Sérgio; Guedes, Carmen Luisa Barbosa; Jordão, Berenice Quinzani

2010-01-01

Polycyclic aromatic hydrocarbons (PAHs) are genotoxic chemicals commonly found in effluents from oil refineries. Bioassays using plants and cells cultures can be employed for assessing environmental safety and potential genotoxicity. In this study, the genotoxic potential of an oil refinery effluent was analyzed by means of micronucleus (MN) testing of Alium cepa, which revealed no effect after 24 h of treatment. On the other hand, primary lesions in the DNA of rat (Rattus norvegicus) hepatoma cells (HTC) were observed through comet assaying after only 2 h of exposure. On considering the capacity to detect DNA damage of a different nature and of these cells to metabolize xenobiotics, we suggest the association of the two bioassays with these cell types, plant (Allium cepa) and mammal (HTC) cells, for more accurately assessing genotoxicity in environmental samples.

Pathway of deoxynivalenol-induced apoptosis in human colon carcinoma cells

International Nuclear Information System (INIS)

Bensassi, Fatma; El Golli-Bennour, Emna; Abid-Essefi, Salwa; Bouaziz, Chayma; Hajlaoui, Mohamed Rabeh; Bacha, Hassen

2009-01-01

The mycotoxin, deoxynivalenol (DON), is generally detected in cereal grains and grain-based food products worldwide. Therefore, DON has numerous toxicological effects on animals and humans. The present investigation was conducted to determine the molecular aspects of DON toxicity on human colon carcinoma cells (HT 29). To this aim, we have monitored the effects of DON on (i) cell viability, (ii) Heat shock protein expressions as a parameter of protective and adaptive response, (iii) oxidative damage and (iv) cell death signalling pathway. Our results clearly showed that DON treatment inhibits cell proliferation, did not induce Hsp 70 protein expression and reactive oxygen species generation. We have also demonstrated that this toxin induced a DNA fragmentation followed by p53 and caspase-3 activations. Finally, our findings suggested that oxidative damage is not the major contributor to DON toxicity. This mycotoxin induces direct DNA lesions and could be considered by this fact as a genotoxic agent inducing cell death via an apoptotic process.

Cells behaviors and genotoxicity on topological surface

International Nuclear Information System (INIS)

Yang, N.; Yang, M.K.; Bi, S.X.; Chen, L.; Zhu, Z.Y.; Gao, Y.T.; Du, Z.

2013-01-01

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

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

International Nuclear Information System (INIS)

Klobucar, Goeran I.V.; Stambuk, Anamaria; Srut, Maja; Husnjak, Ivana; Merkas, Martina; Traven, Luka; Cvetkovic, Zelimira

2011-01-01

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.

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.

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

Energy Technology Data Exchange (ETDEWEB)

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

1993-07-01

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

Cytotoxic and genotoxic potential of food-borne nitriles in a liver in vitro model

Science.gov (United States)

Kupke, Franziska; Herz, Corinna; Hanschen, Franziska S.; Platz, Stefanie; Odongo, Grace A.; Helmig, Simone; Bartolomé Rodríguez, María M.; Schreiner, Monika; Rohn, Sascha; Lamy, Evelyn

2016-01-01

Isothiocyanates are the most intensively studied breakdown products of glucosinolates from Brassica plants and well recognized for their pleiotropic effects against cancer but also for their genotoxic potential. However, knowledge about the bioactivity of glucosinolate-borne nitriles in foods is very poor. As determined by GC-MS, broccoli glucosinolates mainly degrade to nitriles as breakdown products. The cytotoxicity of nitriles in human HepG2 cells and primary murine hepatocytes was marginal as compared to isothiocyanates. Toxicity of nitriles was not enhanced in CYP2E1-overexpressing HepG2 cells. In contrast, the genotoxic potential of nitriles was found to be comparable to isothiocyanates. DNA damage was persistent over a certain time period and CYP2E1-overexpression further increased the genotoxic potential of the nitriles. Based on actual in vitro data, no indications are given that food-borne nitriles could be relevant for cancer prevention, but could pose a certain genotoxic risk under conditions relevant for food consumption. PMID:27883018

Modulation of mitomycin C-induced genotoxicity by acetyl- and thio- analogues of salicylic acid.

Science.gov (United States)

Pawar, Amol Ashok; Vikram, Ajit; Tripathi, Durga Nand; Padmanabhan, Shweta; Ramarao, Poduri; Jena, Gopabandhu

2009-01-01

Recent reports regarding acetylsalicylic acid (ASA) and its metabolites suggest suppressive effects against mitomycin C (MMC)-induced genotoxicity in a mice chromosomal aberration assay. Keeping this in mind, the potential anti-genotoxic effect of the thio-analogue of salicylic acid namely thio-salicylic acid (TSA) was speculated upon. The present study investigated and compared the anti-genotoxic potential of ASA and TSA. The study was performed in male swiss mice (20+/-2 g) using single-cell gel electrophoresis and a peripheral blood micronucleus assay. ASA and TSA (5, 10 or 20 mg/kg) were administered 15 minutes after MMC (1 mg/kg) once daily for 3 or 7 days. Both ASA and TSA significantly decreased the DNA damage induced by MMC as indicated by a decrease in the comet parameters in bone marrow cells and decreased frequencies of micronucleated reticulocytes in peripheral blood. The results clearly demonstrate the anti-genotoxic potential of ASA and TSA.

In Vitro Genotoxic Effects of Four Helichrysum Species in Human Lymphocytes Cultures

OpenAIRE

Erolu, Erhan H; Hamzaolu, Ergin; Aksoy, Ahmet; Budak, Ümit; Özkul, Yusuf

2010-01-01

Helichrysum sanguineum, Helichrysum pamphylicum, Helichrysum orientale, Helichrysum noeanum (Asteraceae) are medicinal plants. For centuries, they have been used as tea in Turkey because of their medicinal properties. So far no scientifc evidence has been found in a literature survey regarding the genotoxic effects of these plants. This work evaluated the genotoxic effects on human lymphocyte cultures induced by methanol extracts of these plants, assayed in different concentrations (0.01, 0.0...

Genotoxicity assessment data for exfoliated buccal cells exposed to mobile phone radiation

Directory of Open Access Journals (Sweden)

F.M. de Oliveira

2017-12-01

Full Text Available Healthy mobile phone users aged 18–30 y.o. provided exfoliated buccal cells samples from the right and left inner cheeks. A total of 2000 cells per subject were screened for the presence of micronuclei as a sign of genotoxic damage, according to the mobile phone use profile of each user. Keywords: Electromagnetic fields, Mobile phones, Genotoxicity, Micronuclei, Exfoliated buccal cells, Feulgen stain

Colonic lymphoid follicles associated with colonic neoplasms

International Nuclear Information System (INIS)

Glick, S.N.; Teplick, S.K.; Ross, W.M.

1986-01-01

The authors prospectively evaluated 62 patients over 40 years old in whom lymphoid follicles were demonstrated on double-contrast enema examinations. Eighteen patients (29%) had no current radiographic evidence of, or history of, colonic neoplasms. Forty-four patients (71%) had an associated neoplasm. Fourteen patients had associated colonic carcinoma, and ten patients had a history of a previously resected colon cancer. One patient had previously undergone resection for ''polyps.'' Twenty-two patients had an associated ''polyp.'' There were no clinical or radiographic features that could reliably distinguish the neoplastic from the nonneoplastic groups. However, lymphoid follicles in the left colon or diffusely involving the colon were more likely to be associated with a colonic neoplasm. Lymphoid follicles were almost always identified near a malignant lesion

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.

Genotoxic effect of radio marked lymphocytes using Tc-99m complexes

International Nuclear Information System (INIS)

Pedraza L, M.; Ferro F, G.; Mendiola C, M.T.; Morales R, P.

1997-01-01

The genotoxic effect of radio marked lymphocytes was evaluated using 99m -Tc-HMPAO and 99m -Tc- gentisic acid complexes. With the results of this work it is pretended to contribute to the knowledge of genetic and structural damages that provokes the radiation in the marked lymphocytes. The d, 1-HMPAO was synthesized in laboratory with a yielding of 30 %. The radiochemical purity of the complexes was greater than 85%. Mouse lymphocytes obtained of sanguineous volumes 2 ml were used. The radio marked efficiency of cells was 19.6 ± 6.4% and 25.6 ± 5.8% for 99m Tc-HMPAO and 99m Tc gentisic acid respectively. The genotoxic effect was evaluated using the technique of Unicellular Electrophoresis in Micro gel (Comet assay). The results showed that both 99m Tc complexes produce genotoxicity due to their capacity to penetrate cells, therefore the Auger and M internal conversion electrons place all their energy obtaining doses of Gray order. (Author)

Genotoxic evaluation of an industrial effluent from an oil refinery using plant and animal bioassays

Directory of Open Access Journals (Sweden)

Fernando Postalli Rodrigues

2010-01-01

Full Text Available Polycyclic aromatic hydrocarbons (PAHs are genotoxic chemicals commonly found in effluents from oil refineries. Bioassays using plants and cells cultures can be employed for assessing environmental safety and potential genotoxicity. In this study, the genotoxic potential of an oil refinery effluent was analyzed by means of micronucleus (MN testing of Alium cepa, which revealed no effect after 24 h of treatment. On the other hand, primary lesions in the DNA of rat (Rattus norvegicus hepatoma cells (HTC were observed through comet assaying after only 2 h of exposure. On considering the capacity to detect DNA damage of a different nature and of these cells to metabolize xenobiotics, we suggest the association of the two bioassays with these cell types, plant (Allium cepa and mammal (HTC cells, for more accurately assessing genotoxicity in environmental samples.

CT Findings of Colonic Complications Associated with Colon Cancer

International Nuclear Information System (INIS)

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

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.

Conventional and whitening toothpastes: cytotoxicity, genotoxicity and effect on the enamel surface.

Science.gov (United States)

Camargo, Samira Esteves Afonso; Jóias, Renata Pilli; Santana-Melo, Gabriela Fátima; Ferreira, Lara Tolentino; El Achkar, Vivian Narana Ribeiro; Rode, Sigmar de Mello

2014-12-01

To evaluate the cytotoxicity and genotoxicity of whitening and common toothpastes, and the surface roughness of tooth enamel submitted to brushing with both toothpastes. Samples of whitening toothpastes [Colgate Whitening (CW) and Oral-B Whitening (OBW)] and regular (non-whitening) toothpastes (Colgate and Oral-B) were extracted in culture medium. Gingival human fibroblasts (FMM-1) were placed in contact with different dilutions of culture media that had been previously exposed to such materials, and the cytotoxicity was evaluated using the MTT assay. The genotoxicity was assessed by the micronucleus formation assay in Chinese hamster fibroblasts (V79). The cell survival rate and micronuclei number were assessed before and after exposure to the toothpaste extracts. For the surface roughness evaluation, 20 bovine tooth specimens, divided into four groups according to toothpastes, were submitted to 10,000 brushing cycles. The results were analyzed using the Mann-Whitney U and two-way ANOVA tests (P whitening toothpastes showed the highest numbers of micronuclei compared to the untreated control (UC) (P enamel surface (P whitening toothpastes and Oral-B were cytotoxic to the cells. The whitening toothpastes were more genotoxic to cells in vitro than the common toothpastes, and genotoxicity was more pronounced in the OBW toothpaste.

Genotoxic evaluation of terbinafine in human lymphocytes in vitro.

Science.gov (United States)

Tolomeotti, Danielle; de Castro-Prado, Marialba Avezum Alves; de Sant'Anna, Juliane Rocha; Martins, Ana Beatriz Tozzo; Della-Rosa, Valter Augusto

2015-01-01

Terbinafine is an antimycotic drug usually used against several superficial fungal infections and with a potential application in the treatment of human cancers. Since to date there are few data on the genotoxic effects of terbinafine in mammalian cells, current study evaluated the potential genotoxic of such antifungal agent in cultured human peripheral blood lymphocytes. Terbinafine was used at the peak plasma concentration (1.0 μg/ml) and in four additional concentrations higher than the human plasmatic peak (5.0 μg/ml, 25.0 μg/ml, 50.0 μg/ml and 100.0 μg/ml). Chromosomal aberrations (CA), sister chromatid exchanges (SCE), micronuclei (MN), nucleoplasmic bridges (NP) and nuclear buds (NB) were scored as genetic endpoints. In all analysis no significant differences (α = 0.05, Kruskal-Wallis test) were observed. Complementary criterion adopted to obtain the final response in cytogenetic agreed with statistical results. Therefore, results of this study showed that terbinafine neither induced CA, SCE, MN, NP and NB nor affected significantly mitotic, replication and cytokinesis-block proliferation indices in any of the tested concentrations. It may be assumed that terbinafine was not genotoxic or cytotoxic to cultured human peripheral blood lymphocytes in our experimental conditions.

Size- and coating-dependent cytotoxicity and genotoxicity of silver nanoparticles evaluated using in vitro standard assays.

Science.gov (United States)

Guo, Xiaoqing; Li, Yan; Yan, Jian; Ingle, Taylor; Jones, Margie Yvonne; Mei, Nan; Boudreau, Mary D; Cunningham, Candice K; Abbas, Mazhar; Paredes, Angel M; Zhou, Tong; Moore, Martha M; Howard, Paul C; Chen, Tao

2016-11-01

The physicochemical characteristics of silver nanoparticles (AgNPs) may greatly alter their toxicological potential. To explore the effects of size and coating on the cytotoxicity and genotoxicity of AgNPs, six different types of AgNPs, having three different sizes and two different coatings, were investigated using the Ames test, mouse lymphoma assay (MLA) and in vitro micronucleus assay. The genotoxicities of silver acetate and silver nitrate were evaluated to compare the genotoxicity of nanosilver to that of ionic silver. The Ames test produced inconclusive results for all types of the silver materials due to the high toxicity of silver to the test bacteria and the lack of entry of the nanoparticles into the cells. Treatment of L5718Y cells with AgNPs and ionic silver resulted in concentration-dependent cytotoxicity, mutagenicity in the Tk gene and the induction of micronuclei from exposure to nearly every type of the silver materials. Treatment of TK6 cells with these silver materials also resulted in concentration-dependent cytotoxicity and significantly increased micronucleus frequency. With both the MLA and micronucleus assays, the smaller the AgNPs, the greater the cytotoxicity and genotoxicity. The coatings had less effect on the relative genotoxicity of AgNPs than the particle size. Loss of heterozygosity analysis of the induced Tk mutants indicated that the types of mutations induced by AgNPs were different from those of ionic silver. These results suggest that AgNPs induce cytotoxicity and genotoxicity in a size- and coating-dependent manner. Furthermore, while the MLA and in vitro micronucleus assay (in both types of cells) are useful to quantitatively measure the genotoxic potencies of AgNPs, the Ames test cannot.

In vivo micronucleus test as a biomarker of genotoxicity in free-range goats from suspected contaminated environment

Directory of Open Access Journals (Sweden)

Afusat Jagun Jubril

2017-09-01

Conclusion: The finding indicates the prevalence and frequency of micronucleus as a biomarker of genotoxicity and an indicator of exposure to environmental genotoxic subtances. Hence, this highlights the relevance of these goats as important sentinel animal model. These findings, therefore, serve as a preliminary data for further studies on the latent genotoxic environmental contaminants and their potential deleterious impact. [J Adv Vet Anim Res 2017; 4(3.000: 281-287

Genotoxic Effect of Atrazine, Arsenic, Cadmium and Nitrate ...

African Journals Online (AJOL)

Atrazine has clastogenic effects and may also act as tumor promoter as it induces the aromatase enzyme. ... bladder cancer. This study ... in MCF-10A cells, suggesting that estrogen receptor modulated the genotoxicity of estrogen. Cd caused ...

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.

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

International Nuclear Information System (INIS)

Musa, Marahaini; Ponnuraj, Kannan Thirumulu; 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. (paper)

Genotoxicity and cytotoxicity induced by eluates from orthodontic glass ionomer cements in vitro

Directory of Open Access Journals (Sweden)

Fernanda Angelieri

2018-01-01

Full Text Available The aim of this study was to investigate genotoxicity and cytotoxicity of some orthodontic glass ionomer cements commercially available by means of the single cell gel (comet assay. For this purpose, five commercial orthodontic glass ionomer cements (Vidrion C®, Meron®, Optiband®, Multicure® and Ultra Band Lok® were tested in murine fibroblasts in vitro. For this purpose, eluates from each cement were prepared according manufactures instructions at 0, 2, 4, 8, 18, 32 and 64 days of immersion in artificial saliva at 37 °C. All orthodontic glass ionomer cements failed to induce cytotoxicity to murine fibroblasts for all periods evaluated in this study. However, Vidrion C® was able to induce genotoxicity after 64 days of exposure to eluates. Meron® also demonstrated genotoxicity as depicted by increasing DNA damage on 2nd day. Multicure® demonstrated genotoxicity on 32nd day and Ultra band Lok on 18th, 32nd days of exposure. Taken together, our results demonstrated that orthodontic cements derived from resin-modified glass ionomer composite (Multicure® and compomer (Ultra Band Lok® cause genetic damage in mammalian cells in vitro.

Induction of micronuclei by 2-hydroxypyridine in water and elimination of solution genotoxicity by UVC (254 nm) photolysis

International Nuclear Information System (INIS)

Skoutelis, Charalambos G.; Vlastos, Dimitris; Kortsinidou, Marianna C.; Theodoridis, Ioannis T.; Papadaki, Maria I.

2011-01-01

Highlights: ► 2-Hydroxypyridine (2-HPY) is the major metabolite of 2-halogenated pyridines photolysis. ► We examine the genotoxicity of 2-HPY in cultured human lymphocytes applying the micronucleus assay. ► 2-HPY was found to be genotoxic. ► Aqueous solutions of 2-HPY were irradiated by UV at 254 nm. ► Solution genotoxicity can be completely removed after prolonged phototreatment. - Abstract: 2-Hydroxypyridine (2-HPY) is a major first-stage product formed upon the photolytic destruction of 2-halogenated pyridines. Genotoxicity of 2-HPY in water was studied as a function of concentration. Aqueous solutions of 2-HPY were irradiated by ultraviolet (UV) at 254 nm. 2-HPY concentration, solution total organic carbon (TOC) concentration and solution genotoxicity were measured as a function of treatment time and their profile as a function of time is presented in this work. 2-HPY was found to be genotoxic at all concentrations in the range of 5–400 μg ml −1 . 2-HPY mineralises completely upon prolonged UV irradiation. All untreated and irradiated solution samples, taken at different photo-treatment times, were tested in cultured human lymphocytes applying the cytokinesis block micronucleus (CBMN) assay. The genotoxicity of the solution was reduced near to the control level after prolonged UV irradiation.

Three-Dimensional, Transgenic Cell Models to Quantify Space Genotoxic Effects

Science.gov (United States)

Gonda, S. R.; Sognier, M. A.; Wu, H.; Pingerelli, P. L.; Glickman, B. W.; Dawson, David L. (Technical Monitor)

1999-01-01

The space environment contains radiation and chemical agents known to be mutagenic and carcinogenic to humans. Additionally, microgravity is a complicating factor that may modify or synergize induced genotoxic effects. Most in vitro models fail to use human cells (making risk extrapolation to humans more difficult), overlook the dynamic effect of tissue intercellular interactions on genotoxic damage, and lack the sensitivity required to measure low-dose effects. Currently a need exists for a model test system that simulates cellular interactions present in tissue, and can be used to quantify genotoxic damage induced by low levels of radiation and chemicals, and extrapolate assessed risk to humans. A state-of-the-art, three-dimensional, multicellular tissue equivalent cell culture model will be presented. It consists of mammalian cells genetically engineered to contain multiple copies of defined target genes for genotoxic assessment,. NASA-designed bioreactors were used to coculture mammalian cells into spheroids, The cells used were human mammary epithelial cells (H184135) and Stratagene's (Austin, Texas) Big Blue(TM) Rat 2 lambda fibroblasts. The fibroblasts were genetically engineered to contain -a high-density target gene for mutagenesis (60 copies of lacl/LacZ per cell). Tissue equivalent spheroids were routinely produced by inoculation of 2 to 7 X 10(exp 5) fibroblasts with Cytodex 3 beads (150 micrometers in diameter). at a 20:1 cell:bead ratio, into 50-ml HARV bioreactors (Synthecon, Inc.). Fibroblasts were cultured for 5 days, an equivalent number of epithelial cells added, and the fibroblast/epithelial cell coculture continued for 21 days. Three-dimensional spheroids with diameters ranging from 400 to 600 micrometers were obtained. Histological and immunohistochemical Characterization revealed i) both cell types present in the spheroids, with fibroblasts located primarily in the center, surrounded by epithelial cells; ii) synthesis of extracellular matrix

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.

Non-genotoxic carcinogens: early effects on gap junctions, cell proliferation and apoptosis in the rat

International Nuclear Information System (INIS)

Mally, Angela; Chipman, James Kevin

2002-01-01

Non-genotoxic carcinogens are thought to induce tumour formation by disturbing the balance between cell growth and cell death. Gap junctions (GJ) contribute to the maintenance of tissue homeostasis by allowing the intercellular exchange of growth regulatory signals and potential inhibition of GJ intercellular communication through loss of connexin (Cx) plaques has been shown to be involved in the cancer process. We have investigated the time- and dose-dependent effects of the non-genotoxic hepatocarcinogens Wy-14,643, 2,3,7,8-tetrachlorodibenzo-p-dioxin, methapyrilene and hexachlorobenzene and the male rat kidney carcinogens chloroform, p-dichlorobenzene and d-limonene on gap junction plaque expression in relation to proliferation and apoptosis. With the exception of limonene, all non-genotoxic carcinogens significantly reduced the expression of GJ plaques containing Cx32 in their respective target tissue. No dose-dependent, significant effects were seen in non-target organs. Although alteration of Cx32 expression did not appear to correlate with induction of cell proliferation, out data suggest that the interaction of both processes--interference of GJ coupled with a proliferative stimulus (at the carcinogenic dose)--may be important in non-genotoxic carcinogenesis and provide a potential alert for non-genotoxic carcinogens in short-term toxicity tests

In vitro genotoxic effects of four Helichrysum species in human lymphocytes cultures.

Science.gov (United States)

Erolu, Erhan H; Hamzaolu, Ergin; Aksoy, Ahmet; Budak, Ümit; Özkul, Yusuf

2010-01-01

Helichrysum sanguineum, Helichrysum pamphylicum, Helichrysum orientale, Helichrysum noeanum (Asteraceae) are medicinal plants. For centuries, they have been used as tea in Turkey because of their medicinal properties. So far no scientific evidence has been found in a literature survey regarding the genotoxic effects of these plants. This work evaluated the genotoxic effects on human lymphocyte cultures induced by methanol extracts of these plants, assayed in different concentrations (0.01, 0.05, 0.1, 0.5 and 1 mg/mL). According to the results, Helichrysum noeanum, Helichrysum pamphylicum and Helichrysum sanguineum induced the formation of micronuclei and decreased the mitotic and replication indexes. Helichrysum orientale did not affect these parameters, whereas Helichrysum noeanum, Helichrysum pamphylicum and Helichrysum sanguineum were clearly genotoxic. They should therefore not be used freely in alternative medicine, although their antiproliferative activity may suggest antimitotic and anticarcinogenic properties. Helichrysum orientale could be used in alternative medicine.

Genotoxicity of gemfibrozil in the gilthead seabream (Sparus aurata).

Science.gov (United States)

Barreto, A; Luis, L G; Soares, A M V M; Paíga, P; Santos, L H M L M; Delerue-Matos, C; Hylland, K; Loureiro, S; Oliveira, M

2017-09-01

Widespread use of pharmaceuticals and suboptimal wastewater treatment have led to increased levels of these substances in aquatic ecosystems. Lipid-lowering drugs such as gemfibrozil, which are among the most abundant human pharmaceuticals in the environment, may have deleterious effects on aquatic organisms. We examined the genotoxicity of gemfibrozil in a fish species, the gilthead seabream (Sparus aurata), which is commercially important in southern Europe. Following 96-h waterborne exposure, molecular (erythrocyte DNA strand breaks) and cytogenetic (micronuclei and other nuclear abnormalities in cells) endpoints were measured. Gemfibrozil was positive in both endpoints, at environmentally relevant concentrations, a result that raises concerns about the potential genotoxic effects of the drug in recipient waters. Copyright © 2017 Elsevier B.V. All rights reserved.

Aspect ratio has no effect on genotoxicity of multi-wall carbon nanotubes.

Science.gov (United States)

Kim, Jin Sik; Lee, Kyu; Lee, Young Hee; Cho, Hyun Sun; Kim, Ki Heon; Choi, Kyung Hee; Lee, Sang Hee; Song, Kyung Seuk; Kang, Chang Soo; Yu, Il Je

2011-07-01

Carbon nanotubes (CNTs) have specific physico-chemical and electrical properties that are useful for telecommunications, medicine, materials, manufacturing processes and the environmental and energy sectors. Yet, despite their many advantages, it is also important to determine whether CNTs may represent a hazard to the environment and human health. Like asbestos, the aspect ratio (length:diameter) and metal components of CNTs are known to have an effect on the toxicity of carbon nanotubes. Thus, to evaluate the toxic potential of CNTs in relation to their aspect ratio and metal contamination, in vivo and in vitro genotoxicity tests were conducted using high-aspect-ratio (diameter: 10-15 nm, length: ~10 μm) and low-aspect-ratio multi-wall carbon nanotubes (MWCNTs, diameter: 10-15 nm, length: ~150 nm) according to OECD test guidelines 471 (bacterial reverse mutation test), 473 (in vitro chromosome aberration test), and 474 (in vivo micronuclei test) with a good laboratory practice system. To determine the treatment concentration for all the tests, a solubility and dispersive test was performed, and a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) solution found to be more suitable than distilled water. Neither the high- nor the low-aspect-ratio MWCNTs induced any genotoxicity in a bacterial reverse mutation test (~1,000 μg/plate), in vitro chromosome aberration test (without S9: ~6.25 μg/ml, with S9: ~50 μg/ml), or in vivo micronuclei test (~50 mg/kg). However, the high-aspect-ratio MWCNTs were found to be more toxic than the low-aspect-ratio MWCNTs. Thus, while high-aspect-ratio MWCNTs do not induce direct genotoxicity or metabolic activation-mediated genotoxicity, genotoxicity could still be induced indirectly through oxidative stress or inflammation.

Mercury-induced genotoxicity in marine diatom (Chaetoceros tenuissimus)

Digital Repository Service at National Institute of Oceanography (India)

Sarker, S.; Desai, S.R.; Verlecar, X.N.; Sarker, M.S.; Sarkar, A.

In this paper, we present an evaluation of genotoxic responses in marine diatom, Chaetoceros tenuissimus, isolated from Kandla Creek (lat 23.03° N, long 70.22° E), Gujarat, India, in terms of impairment of DNA integrity as a function...

Genotoxic Properties of 2-Dodecylcyclobutanone, a Compound Formed on Irradiation of Food Containing Fat

International Nuclear Information System (INIS)

Delincee, Henry; Pool-Zobel, Beatrice-Louise

1998-01-01

When food containing fat is treated by ionizing radiation, a group of 2-alkylcyclobutanones is formed. These components contain the same number of carbon atoms as their precursor fatty acids and the alkyl group is located in ring position 2. Thus, from palmitic acid 2-dodecylcyclobutanone is derived. To date, there is no evidence that the cyclobutanones occur in unirradiated food. Therefore, these components cannot be considered inherent to food, and for questions pertaining to risk assessment of irradiated food it would be advisable to determine the genotoxic and toxic potentials of cyclobutanones. Measurements of DNA damage in cells exposed to 2-dodecylcyclobutanone, employing the single cell microgel electrophoresis technique, have been carried out. In vitro experiments using rat and human colon cells indicate that 2-dodecylcyclobutanone in the concentration range of about 0.30-1.25 mg/ml induces DNA strand breaks in the cells. Simultaneously, a concentration related cytotoxic effect is observed as was determined by trypan blue exclusion. To which extent these in vitro findings are of relevancy for the in vivo human exposure situation needs to be investigated in further studies. In vivo tests in rats are in progress

[Genotoxic damage among artisanal and small-scale mining workers exposed to mercury].

Science.gov (United States)

Rosales-Rimache, Jaime A; Elizabeth Malca, Nancy; Alarcón, Jhonatan J; Chávez, Manuel; Gonzáles, Marco Antonio

2013-01-01

To determine the genotoxic damage among artisanal and small-scale mining workers exposed to mercury. Observational cross-sectional study which evaluated mercury-exposed workers (n=83), whose cells were collected by mouth swab for further staining, microscopic observance, micronuclei count, and other nuclear alterations. 24-hour urine was also collected for the determination of inorganic mercury. 68.7% of participants were male, the mean age being 43 ± 12,4 years (range: 16-76). The average time of occupational exposure to mercury was 12,1 ± 6,7 years, and the contact with mercury was 4,1 ± 3,6 kg per person per day. 93% of participants failed to wear personal protection gear while handling mercury. Results of biological monitoring showed that 17% of participants had concentrations of mercury in urine higher than 2,5 µg/L, this value being the detection limit of the measurement technique used. Results of the genotoxic evaluation evidenced that 15% of people with labor exposure to mercury presented micronuclei in mouth epithelial cells, and other indicators of nuclear alteration such as nucleoplasmic bridges, gemmation and binucleation were found, which are also considered genotoxic events associated to the exposure of physical or chemical risk agents. The finding of micronuclei in mouth epithelial cells reflects genotoxic damage associated to the labor exposure of mercury used in artisanal and small-scale mining activities.

High Dose Ascorbate Causes Both Genotoxic and Metabolic Stress in Glioma Cells

Science.gov (United States)

Castro, Maria Leticia; Carson, Georgia M.; McConnell, Melanie J.; Herst, Patries M.

2017-01-01

We have previously shown that exposure to high dose ascorbate causes double stranded breaks (DSBs) and a build-up in S-phase in glioblastoma (GBM) cell lines. Here we investigated whether or not this was due to genotoxic stress as well as metabolic stress generated by exposure to high dose ascorbate, radiation, ascorbate plus radiation and H2O2 in established and primary GBM cell lines. Genotoxic stress was measured as phosphorylation of the variant histone protein, H2AX, 8-oxo-7,8-dihydroguanine (8OH-dG) positive cells and cells with comet tails. Metabolic stress was measured as a decrease in NADH flux, mitochondrial membrane potential (by CMXRos), ATP levels (by ATP luminescence) and mitochondrial superoxide production (by mitoSOX). High dose ascorbate, ascorbate plus radiation, and H2O2 treatments induced both genotoxic and metabolic stress. Exposure to high dose ascorbate blocked DNA synthesis in both DNA damaged and undamaged cell of ascorbate sensitive GBM cell lines. H2O2 treatment blocked DNA synthesis in all cell lines with and without DNA damage. DNA synthesis arrest in cells with damaged DNA is likely due to both genotoxic and metabolic stress. However, arrest in DNA synthesis in cells with undamaged DNA is likely due to oxidative damage to components of the mitochondrial energy metabolism pathway. PMID:28737676

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.

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 po...

In vitro and in vivo genotoxicity of 1,3-butadiene and metabolites.

OpenAIRE

Arce, G T; Vincent, D R; Cunningham, M J; Choy, W N; Sarrif, A M

1990-01-01

1,3-Butadiene and two major genotoxic metabolites 3,4-epoxybutene (EB) and 1,2:3,4-diepoxybutane (DEB) were used as model compounds to determine if genetic toxicity findings in animal and human cells can aid in extrapolating animal toxicity data to man. Sister chromatid exchange (SCE) and micronucleus induction results indicated 1,3-butadiene was genotoxic in the bone marrow of the mouse but not the rat. This paralleled the chronic bioassays which showed mice to be more susceptible than rats ...

Genotoxicity of two heavy metal compounds: lead nitrate and cobalt chloride in Polychaete Perinereis cultrifera.

Science.gov (United States)

Singh, Nisha; Bhagat, Jacky; Ingole, Baban S

2017-07-01

The present study explores the in vivo and in vitro genotoxic effects of lead nitrate, [Pb(NO 3 ) 2 ] a recognized environmental pollutant and cobalt chloride (CoCl 2 ), an emerging environmental pollutant in polychaete Perinereis cultrifera using comet assay. Despite widespread occurrence and extensive industrial applications, no previous published reports on genotoxicity of these compounds are available in polychaete as detected by comet assay. Polychaetes were exposed in vivo to Pb(NO 3 ) 2 (0, 100, 500, and 1000 μg/l) and CoCl 2 (0, 100, 300, and 500 μg/l) for 5 days. At 100 μg/l Pb(NO 3 ) 2 concentration, tail DNA (TDNA) values in coelomocytes were increase by 1.16, 1.43, and 1.55-fold after day 1, day 3, and day 5, whereas, OTM showed 1.12, 2.33, and 2.10-fold increase in in vivo. Pb(NO 3 ) 2 showed a concentration and time-dependent genotoxicity whereas CoCl 2 showed a concentration-dependent genotoxicity in in vivo. A concentration-dependent increase in DNA damage was observed in in vitro studies for Pb(NO 3 ) 2 and CoCl 2 . DNA damage at 500 μg/L showed almost threefold increase in TDNA and approximately fourfold increase in OTM as compared to control in in vitro. Our studies suggest that Pb(NO 3 ) 2 and CoCl 2 have potential to cause genotoxic damage, with Pb(NO 3 ) 2 being more genotoxic in polychaete and should be used more carefully in industrial and other activities. Graphical abstract.

Genotoxicity of indium tin oxide by comet test

Directory of Open Access Journals (Sweden)

İbrahim Hakkı Ciğerci

2015-06-01

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

Metabolic profile and genotoxicity in obese rats exposed to cigarette smoke.

Science.gov (United States)

Damasceno, Debora C; Sinzato, Yuri K; Bueno, Aline; Dallaqua, Bruna; Lima, Paula H; Calderon, Iracema M P; Rudge, Marilza V C; Campos, Kleber E

2013-08-01

Experimental studies have shown that exposure to cigarette smoke has negative effects on lipid metabolism and oxidative stress status. Cigarette smoke exposure in nonpregnant and pregnant rats causes significant genotoxicity (DNA damage). However, no previous studies have directly evaluated the effects of obesity or the association between obesity and cigarette smoke exposure on genotoxicity. Therefore, the aim of the present investigation was to evaluate DNA damage levels, oxidative stress status and lipid profiles in obese Wistar rats exposed to cigarette smoke. Female rats subcutaneously (s.c.) received a monosodium glutamate solution or vehicle (control) during the neonatal period to induce obesity. The rats were randomly distributed into three experimental groups: control, obese exposed to filtered air, and obese exposed to tobacco cigarette smoke. After a 2-month exposure period, the rats were anesthetized and killed to obtain blood samples for genotoxicity, lipid profile, and oxidative stress status analyses. The obese rats exposed to tobacco cigarette smoke presented higher DNA damage, triglycerides, total cholesterol, free fatty acids, VLDL-c, HDL-c, and LDL-c levels compared to control and obese rats exposed to filtered air. Both obese groups showed reduced SOD activity. These results showed that cigarette smoke enhanced the effects of obesity. In conclusion, the association between obesity and cigarette smoke exposure exacerbated the genotoxicity, negatively impacted the biochemical profile and antioxidant defenses and caused early glucose intolerance. Thus, the changes caused by cigarette smoke exposure can trigger the earlier onset of metabolic disorders associated with obesity, such as diabetes and metabolic syndrome. Copyright © 2012 The Obesity Society.

Evaluation of the genotoxicity of cellulose nanofibers.

Science.gov (United States)

de Lima, Renata; Oliveira Feitosa, Leandro; Rodrigues Maruyama, Cintia; Abreu Barga, Mariana; Yamawaki, Patrícia Cristina; Vieira, Isolda Jesus; Teixeira, Eliangela M; Corrêa, Ana Carolina; Caparelli Mattoso, Luiz Henrique; Fernandes Fraceto, Leonardo

2012-01-01

Agricultural products and by products provide the primary materials for a variety of technological applications in diverse industrial sectors. Agro-industrial wastes, such as cotton and curaua fibers, are used to prepare nanofibers for use in thermoplastic films, where they are combined with polymeric matrices, and in biomedical applications such as tissue engineering, amongst other applications. The development of products containing nanofibers offers a promising alternative for the use of agricultural products, adding value to the chains of production. However, the emergence of new nanotechnological products demands that their risks to human health and the environment be evaluated. This has resulted in the creation of the new area of nanotoxicology, which addresses the toxicological aspects of these materials. Contributing to these developments, the present work involved a genotoxicological study of different nanofibers, employing chromosomal aberration and comet assays, as well as cytogenetic and molecular analyses, to obtain preliminary information concerning nanofiber safety. The methodology consisted of exposure of Allium cepa roots, and animal cell cultures (lymphocytes and fibroblasts), to different types of nanofibers. Negative controls, without nanofibers present in the medium, were used for comparison. The nanofibers induced different responses according to the cell type used. In 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. 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

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

International Nuclear Information System (INIS)

Klumpp, Andreas; Ansel, Wolfgang; Klumpp, Gabriele; Calatayud, Vicent; Garrec, Jean Pierre; He Shang; Penuelas, Josep; Ribas, Angela; Ro-Poulsen, Helge; Rasmussen, Stine; Sanz, Maria Jose; Vergne, Phillippe

2006-01-01

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

Genotoxic effects of N-nitrosodimethylamine in somatic and generative cells of mice

Directory of Open Access Journals (Sweden)

Anna V. Lovinskaya

2017-10-01

Full Text Available N-Nitrosodimethylamine (NDMA was shown to have genotoxic properties in acute and subacute studies on laboratory mice. The organ-specificity of the genotoxic effect of NDMA was revealed using the Comet assay. The most sensitive organs to the action of NDMA were kidneys and liver. DNA damage in liver cells of NDMA-treated animals at doses of 4.0 and 8.0 mg/kg, increased compared to control in 6.9 and 12.5 (р < 0.001, and in kidney cells – in 8.1 and 14.2 times (р < 0.001, respectively. NDMA also showed genotoxic activity in the reproductive cells of experimental animals, causing structural disorders of synaptonemal complexes in spermatocyte. In NDMA-treated animals at a dose of 2.0 mg/kg in acute and subacute studies, the level of spermatocytes with damaged synaptonemal complexes increased statistically significantly compared to control in 6.0 and 7.0 (р < 0.05 times, respectively.

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.

In Vitro Genotoxic Effects of Four Helichrysum Species in Human Lymphocytes Cultures

Directory of Open Access Journals (Sweden)

Erhan H Erolu

2010-01-01

Full Text Available Helichrysum sanguineum, Helichrysum pamphylicum, Helichrysum orientale, Helichrysum noeanum (Asteraceae are medicinal plants. For centuries, they have been used as tea in Turkey because of their medicinal properties. So far no scientifc evidence has been found in a literature survey regarding the genotoxic effects of these plants. This work evaluated the genotoxic effects on human lymphocyte cultures induced by methanol extracts of these plants, assayed in different concentrations (0.01, 0.05, 0.1, 0.5 and 1 mg/mL. According to the results, Helichrysum noeanum, Helichrysum pamphylicum and Helichrysum sanguineum induced the formation of micronuclei and decreased the mitotic and replication indexes. Helichrysum orientale did not affect these parameters, whereas Helichrysum noeanum, Helichrysum pamphylicum and Helichrysum sanguineum were clearly genotoxic. They should therefore not be used freely in alternative medicine, although their antiproliferative activity may suggest antimitotic and anticarcinogenic properties. Helichrysum orientale could be used in alternative medicine.

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.

Genotoxicity studies on DNA-interactive telomerase inhibitors with application as anti-cancer agents.

Science.gov (United States)

Harrington, Dean J; Cemeli, Eduardo; Carder, Joanna; Fearnley, Jamie; Estdale, Sian; Perry, Philip J; Jenkins, Terence C; Anderson, Diana

2003-01-01

Telomerase-targeted strategies have aroused recent interest in anti-cancer chemotherapy, because DNA-binding drugs can interact with high-order tetraplex rather than double-stranded (duplex) DNA targets in tumour cells. However, the protracted cell-drug exposure times necessary for clinical application require that telomerase inhibitory efficacy must be accompanied by both low inherent cytotoxicity and the absence of mutagenicity/genotoxicity. For the first time, the genotoxicity of a number of structurally diverse DNA-interactive telomerase inhibitors is examined in the Ames test using six Salmonella typhimurium bacterial strains (TA1535, TA1537, TA1538, TA98, TA100, and TA102). DNA damage induced by each agent was also assessed using the Comet assay with human lymphocytes. The two assay procedures revealed markedly different genotoxicity profiles that are likely to reflect differences in metabolism and/or DNA repair between bacterial and mammalian cells. The mutational spectrum for a biologically active fluorenone derivative, shown to be mutagenic in the TA100 strain, was characterised using a novel and rapid assay method based upon PCR amplification of a fragment of the hisG46 allele, followed by RFLP analysis. Preliminary analysis indicates that the majority (84%) of mutations induced by this compound are C --> A transversions at position 2 of the missense proline codon of the hisG46 allele. However, despite its genotoxic bacterial profile, this fluorenone agent gave a negative response in the Comet assay, and demonstrates how unwanted systemic effects (e.g., cytotoxicity and genotoxicity) can be prevented or ameliorated through suitable molecular fine-tuning of a candidate drug in targeted human tumour cells. Copyright 2003 Wiley-Liss, Inc.

A Case of Sigmoid Colon Tuberculosis Mimicking Colon Cancer

OpenAIRE

Yu, Seong-Min; Park, Jong-Hwan; Kim, Min-Dae; Lee, Hee-Ryong; Jung, Peel; Ryu, Tae-Hyun; Choi, Seung-Ho; Lee, Il-Seon

2012-01-01

Tuberculosis of the sigmoid colon is a rare disorder. An 80-year-old man visited Bongseng Memorial Hospital for medical examination. A colonoscopy was performed, and a lesion in the sigmoid colon that was suspected to be colon cancer was found. A biopsy was performed, and tuberculous enteritis with chronic granulomatous inflammation was diagnosed. Intestinal tuberculosis is most frequent in the ileocecal area, followed by the ascending colon, transverse colon, duodenum, stomach, and sigmoid c...

Comparative potency approach based on H2AX assay for estimating the genotoxicity of polycyclic aromatic hydrocarbons.

Science.gov (United States)

Audebert, M; Zeman, F; Beaudoin, R; Péry, A; Cravedi, J-P

2012-04-01

Polycyclic Aromatic Hydrocarbons (PAHs) constitute a family of over one hundred compounds and can generally be found in complex mixtures. PAHs metabolites cause DNA damage which can lead to the development of carcinogenesis. Toxicity assessment of PAH complex mixtures is currently expressed in terms of toxic equivalents, based on Toxicity Equivalent Factors (TEFs). However, the definition of new TEFs for a large number of PAH could overcome some limitations of the current method and improve cancer risk assessment. The current investigation aimed at deriving the relative potency factors of PAHs, based on their genotoxic effect measured in vitro and analyzed with mathematical models. For this purpose, we used a new genotoxic assay (γH2AX) with two human cell lines (HepG2 and LS-174T) to analyze the genotoxic properties of 13 selected PAHs at low doses after 24h treatment. The dose-response for genotoxic effects was modeled with a Hill model; equivalency between PAHs at low dose was assessed by applying constraints to the model parameters. In the two cell lines tested, we observed a clear dose-response for genotoxic effects for 11 tested compounds. LS-174T was on average ten times more sensitive than HepG2 towards PAHs regarding genotoxicity. We developed new TEFs, which we named Genotoxic Equivalent Factor (GEF). Calculated GEF for the tested PAHs were generally higher than the TEF usually used. Our study proposed a new in vitro based method for the establishment of relevant TEFs for PAHs to improve cancer risk assessment. Copyright © 2012 Elsevier Inc. All rights reserved.

Evaluation of genotoxic potential of neurotoxin anatoxin-a with the use of umuC test.

Science.gov (United States)

Sieroslawska, Anna; Rymuszka, Anna

2010-01-01

The aim of this study was to evaluate genotoxicity of anatoxin-a, cyanotoxin of neurotoxic activity. Additionally, other frequently detected cyanotoxin of previously described genotoxic potential, microcystin-LR, was used at the same concentrations, as well as the mixture of both toxins, anatoxin-a and microcystin-LR. Genotoxicity of the toxins was determined with the use of the umuC assay, in which the induction and expression of the umuC - lacZ reporter gene was assessed. The test was conducted on Salmonella typhimurium TA 1535/pSK1002 strain, with and without metabolic transformation. The toxin concentrations were 0.25, 0.5, 1 and 2 µg/ml. The exposure time was 2 h. The highest inefficient concentration of anatoxin-a without metabolic transformation was 0.25 µg/ml, of microcystin-LR was 0.5 µg/ml and in case of the toxin mixture all used concentrations induced the umuC gene. When S9 fraction was added to the samples, no effects were detected. To our knowledge, this is the first report on genotoxic effects of anatoxin-a. Although the study is preliminary and needs further research, however, indicates the new potential activity of the toxin, as well as the possible increase of genotoxicity of other cyanotoxins, more stable in the environment, e.g. microcystin-LR.

The natural triterpene maslinic acid induces apoptosis in HT29 colon cancer cells by a JNK-p53-dependent mechanism

International Nuclear Information System (INIS)

Reyes-Zurita, Fernando J; Pachón-Peña, Gisela; Lizárraga, Daneida; Rufino-Palomares, Eva E; Cascante, Marta; Lupiáñez, José A

2011-01-01

Maslinic acid, a pentacyclic triterpene found in the protective wax-like coating of the leaves and fruit of Olea europaea L., is a promising agent for the prevention of colon cancer. We have shown elsewhere that maslinic acid inhibits cell proliferation to a significant extent and activates mitochondrial apoptosis in colon cancer cells. In our latest work we have investigated further this compound's apoptotic molecular mechanism. We used HT29 adenocarcinoma cells. Changes genotoxicity were analyzed by single-cell gel electrophoresis (comet assay). The cell cycle was determined by flow cytometry. Finally, changes in protein expression were examined by western blotting. Student's t-test was used for statistical comparison. HT29 cells treated with maslinic acid showed significant increases in genotoxicity and cell-cycle arrest during the G0/G1 phase after 72 hours' treatment and an apoptotic sub-G0/G1 peak after 96 hours. Nevertheless, the molecular mechanism for this cytotoxic effect of maslinic acid has never been properly explored. We show here that the anti-tumoral activity of maslinic acid might proceed via p53-mediated apoptosis by acting upon the main signaling components that lead to an increase in p53 activity and the induction of the rest of the factors that participate in the apoptotic pathway. We found that in HT29 cells maslinic acid activated the expression of c-Jun NH2-terminal kinase (JNK), thus inducing p53. Treatment of tumor cells with maslinic acid also resulted in an increase in the expression of Bid and Bax, repression of Bcl-2, release of cytochrome-c and an increase in the expression of caspases -9, -3, and -7. Moreover, maslinic acid produced belated caspase-8 activity, thus amplifying the initial mitochondrial apoptotic signaling. All these results suggest that maslinic acid induces apoptosis in human HT29 colon-cancer cells through the JNK-Bid-mediated mitochondrial apoptotic pathway via the activation of p53. Thus we propose

Initial hazard screening for genotoxicity of photo-transformation products of ciprofloxacin by applying a combination of experimental and in-silico testing

International Nuclear Information System (INIS)

Toolaram, Anju Priya; Haddad, Tarek; Leder, Christoph; Kümmerer, Klaus

2016-01-01

Ciprofloxacin (CIP) is a broad-spectrum antibiotic found within μg/L concentration range in the aquatic environment. It is a known contributor of umuC induction in hospital wastewater samples. CIP can undergo photolysis to result in many transformation products (TPs) of mostly unknown toxicity. The aims of this study were to determine the genotoxicity of the UV mixtures and to understand the possible genotoxic role of the stable TPs. As such, CIP and its UV-irradiated mixtures were investigated in a battery of genotoxicity and cytotoxicity in vitro assays. The combination index (CI) analysis of residual CIP in the irradiated mixtures was performed for the umu assay. Further, Quantitative Structure–Activity Relationships (QSARs) predicted selected genotoxicity endpoints of the identified TPs. CIP achieved primary elimination after 128 min of irradiation but was not completely mineralized. Nine photo-TPs were identified. The irradiated mixtures were neither mutagenic in the Ames test nor genotoxic in the in vitro micronucleus (MN) test. Like CIP, the irradiated mixtures were umuC inducing. The CI analysis revealed that the irradiated mixtures and the corresponding CIP concentration in the mixtures shared similar umuC potentials. QSAR predictions suggested that the TPs may be capable of inducing chromosome aberration, MN in vivo, bacterial mutation and mammalian mutation. However, the experimental testing for a few genotoxic endpoints did not show significant genotoxic activity for the TPs present as a component of the whole mixture analysis and therefore, further genotoxic endpoints may need to be investigated to fully confirm this. - Highlights: • Identified photo-transformation products (TPs) retained the quinolone core. • Experimental and in silico tools assessed for genotoxicity of TPs in the mixtures. • Some of the TPs were predicted as genotoxic by QSAR analysis. • Irradiated mixtures were neither micronuclei inducing nor mutagenic in Ames test

Ecotoxicity and genotoxicity assessment of cytostatic pharmaceuticals

Czech Academy of Sciences Publication Activity Database

Zounková, R.; Odráška, P.; Doležalová, L.; Hilscherová, Klára; Maršálek, Blahoslav; Bláha, Luděk

2007-01-01

Roč. 26, č. 10 (2007), s. 2208-2214 ISSN 0730-7268 Grant - others:GA MŠk(CZ) 2B06171; ECODIS(XE) 518043-1 Institutional research plan: CEZ:AV0Z60050516 Source of funding: R - rámcový projekt EK Keywords : cytostatic pharmaceuticals * genotoxicity * antineoplastics Subject RIV: EF - Botanics Impact factor: 2.309, year: 2007

Genoprotective and Genotoxic Effects of Thymoquinone on ...

African Journals Online (AJOL)

Comet assays and apoptotic cell studies were performed to evaluate the effect of TQ on the cytotoxicity and genotoxicity-induced by DXR. Results: TQ treatment, alone, (5.0, 10, or 20 µM) increased DNA damage index (DI) in a concentrationdependent manner (0.64 ± 0.09, 0.84 ± 0.07, and 0.93 ± 0.06, respectively).

In vitro evaluation of mutagenicity and genotoxicity of sitagliptin ...

African Journals Online (AJOL)

Keywords: Sitagliptin, Artificial sweeteners, Comet assay, DNA damage, Ames assay, Genotoxicity,. Mutagenicity. Tropical Journal of Pharmaceutical Research is indexed by Science Citation Index (SciSearch), Scopus,. International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African.

In vivo genotoxicity evaluation of an artichoke (Cynara scolymus L.) aqueous extract.

Science.gov (United States)

Zan, Meriele A; Ferraz, Alexandre B F; Richter, Marc F; Picada, Jaqueline N; de Andrade, Heloisa H R; Lehmann, Mauricio; Dihl, Rafael R; Nunes, Emilene; Semedo, Juliane; Da Silva, Juliana

2013-02-01

The Cynara scolymus (artichoke) is widely consumed as tea or food and shows important therapeutic properties. However, few studies have assessed the possible toxic effects of artichoke extracts. This study evaluates genotoxic and mutagenic activities of artichoke leaf aqueous extract in mice using the comet assay and the micronucleus test. Leaf extracts were given by gavage (500 mg/kg, 1000 mg/kg, and 2000 mg/kg) for 3 consecutive days. Extract composition was investigated using phytochemical screening and high-performance liquid chromatography (HPLC). In addition, antioxidant capacity was analyzed through the diphenyl-picrylhydrazyl (DPPH) and xanthine oxidase assay. Phytochemical screening detected the presence of phenolic compounds, flavonoids, and saponins. HPLC analyses indicated the presence of chlorogenic acid, caffeic acid, isoquercetrin, and rutin. Extracts showed a dose-dependent free radical scavenging effect of DPPH and an inhibitory effect of xanthine oxidase. The genotoxic results showed that leaf extracts did not increase micronuclei in peripheral blood cells. Compared to the control group, a significant increase in comet assay values was observed only in bone marrow of group treated with 2000 mg/kg, the highest dose tested, indicating that artichoke tea should be consumed with moderation. This is the first report of in vivo mutagenic and genotoxic evaluation with C. scolymus. The present study revealed leaf aqueous extract from artichoke shows lack of mutagenicity in vivo, and low genotoxicity and antioxidant activity; indicating that artichoke tea should be consumed with moderation. © 2013 Institute of Food Technologists®

Oxcarbazepine-induced cytotoxicity and genotoxicity in human lymphocyte cultures with or without metabolic activation.

Science.gov (United States)

Atlı Şekeroğlu, Zülal; Kefelioğlu, Haluk; Kontaş Yedier, Seval; Şekeroğlu, Vedat; Delmecioğlu, Berrin

2017-03-01

There has been considerable debate about the relationship between epilepsy and cancer. Oxcarbazepine (OXC) is used for treating certain types of seizures in patients with epilepsy. There have been no detailed investigations about genotoxicity of OXC and its metabolites. Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of OXC and its metabolites on cultured human lymphocytes. The cytotoxicity and genotoxicity of OXC on human peripheral blood lymphocytes were examined in vitro by sister chromatid exchange (SCE), chromosomal aberration (CA) and micronucleus (MN) tests. Cultures were treated with 125, 250 and 500 μg/ml of OXC in the presence (3 h treatment) and absence (24 h and 48 h treatment) of a metabolic activator (S9 mix). Dimethyl sulfoxide (DMSO) was used as a solvent control. OXC showed cytotoxic activities due to significant decreases in mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) in the absence of S9 mix when compared with solvent control. Metabolites of OXC also significantly reduced MI and PI in cultures with S9 mix. OXC significantly increased the CAs, aberrant cells, SCE and MN values in the presence and absence of S9 mix. Our results indicated that both OXC and its metabolites have cytotoxic, cytostatic and genotoxic potential on human peripheral blood lymphocyte cultures under the experimental conditions. Further studies are necessary to elucidate the relationship between cytotoxic, cytostatic and genotoxic effects, and to make a possible risk assessment in patients receiving therapy with this drug.

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

International Nuclear Information System (INIS)

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

2014-01-01

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. (paper)

Histopathological and genotoxic effects of chlorpyrifos in rats.

Science.gov (United States)

Ezzi, Lobna; Belhadj Salah, Imen; Haouas, Zohra; Sakly, Amina; Grissa, Intissar; Chakroun, Sana; Kerkeni, Emna; Hassine, Mohsen; Mehdi, Meriem; Ben Cheikh, Hassen

2016-03-01

This study aims to investigate the effects of chlorpyrifos's sub-acute exposure on male rats. Two groups with six animals each were orally treated, respectively, with 3.1 mg/kg b w and 6.2 mg/kg b w of chlorpyrifos during 4 weeks. The genotoxic effect of chlopyrifos was investigated using the comet assay and the micronucleus test. Some hematological and liver's histopathological changes were also evaluated. Results revealed that chlorpyrifos induced histopathological alterations in liver parenchyma. The lymphoid infiltration observed in liver sections and the increase in white blood cells parameter are signs of inflammation. A significant increase in the platelet' count and in polychromatic erythrocytes/normochromatic erythrocytes (PCE/NCE) ratio was observed in chlorpyrifos-treated groups which could be due to the stimulatory effect of chlorpyrifos on cell formation in the bone marrow at lower doses. In addition, the increase of bone marrow micronucleus percentage and the comet tail length revealed a genotoxic potential of chlorpyrifos in vivo.

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. Environm......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...

Genotoxic and teratogenic potential of marine sediment extracts investigated with comet assay and zebrafish test

International Nuclear Information System (INIS)

Kammann, Ulrike; Biselli, Scarlett; Huehnerfuss, Heinrich; Reineke, Ninja; Theobald, Norbert; Vobach, Michael; Wosniok, Werner

2004-01-01

Organic extracts of marine sediments from the North Sea and the Baltic Sea were investigated with two toxicity assays. The comet assay based on the fish cell line Epithelioma papulosum cyprini (EPC) was applied to determine the genotoxic potential; zebrafish embryos (Danio rerio) were used to quantify the teratogenic potential of the samples. EC 50 values were calculated from dose-response curves for both test systems. Highest teratogenic and genotoxic effects normalised to total organic carbon (TOC) content were detected in sediment samples of different origins. Polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) are not likely to be the causes of the observed effects, as demonstrated by a two-step fractionation procedure of selected extracts. The toxic potential was more pronounced in fractions having polarity higher than those possessed by PAHs and PCBs. The suitability of the two in vitro test systems for assessing genotoxic and teratogenic effects of marine sediment extracts could be demonstrated. - Capsule: In vitro toxicity assays are used to assess genotoxic and teratogenic effects of environmental extracts

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

Directory of Open Access Journals (Sweden)

İbrahim Hakkı Ciğerci

2015-06-01

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

Moesin Is a Biomarker for the Assessment of Genotoxic Carcinogens in Mouse Lymphoma

Science.gov (United States)

Lee, Yoen Jung; Choi, In-Kwon; Sheen, Yhun Yhong; Park, Sue Nie; Kwon, Ho Jeong

2012-01-01

1,2-Dibromoethane and glycidol are well known genotoxic carcinogens, which have been widely used in industry. To identify a specific biomarker for these carcinogens in cells, the cellular proteome of L5178Y mouse lymphoma cells treated with these compounds was analyzed by 2-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry (MS). Of 50 protein spots showing a greater than 1.5-fold increase or decrease in intensity compared to control cells on a 2-D gel, we focused on the candidate biomarker moesin. Western analysis using monoclonal rabbit anti-moesin confirmed the identity of the protein and its increased level of expression upon exposure to the carcinogenic compounds. Moesin expression also increased in cells treated with six additional genotoxic carcinogens, verifying that moesin could serve as a biomarker to monitor phenotypic change upon exposure to genotoxic carcinogens in L5178Y mouse lymphoma cells. PMID:22358511

Use of the Microscreen phage-induction assay to assess the genotoxicity of 14 hazardous industrial wastes

Energy Technology Data Exchange (ETDEWEB)

Houk, V.S.; DeMarini, D.M.

1988-01-01

The Microscreen phage-induction assay, which quantitatively measures the induction of prophage lambda in Escherichia coli WP2s lambda, was used to test 14 crude (unfractionated) hazardous industrial-waste samples for genotoxic activity in the presence and absence of metabolic activation. Eleven of the 14 wastes induced prophage, and induction was observed at concentrations as low as 0.4 picograms per ml. Comparisons between the mutagenicity of these waste samples in Salmonella and their ability to induce prophage lambda indicate that the Microscreen phage-induction assay detected genotoxic activity in all but one of the wastes that were mutagenic in Salmonella. Moreover, the Microscreen assay detected as genotoxic 5 additional wastes that were not detected in the Salmonella assay. The applicability of the Microscreen phage-induction assay for screening hazardous wastes for genotoxic activity is discussed along with some of the problems associated with screening highly toxic wastes containing toxic volatile compounds.

Use of the microscreen phage-induction assay to assess the genotoxicity of 14 hazardous industrial wastes

Energy Technology Data Exchange (ETDEWEB)

Houk, V.S.; DeMarini, D.M.

1988-01-01

The Microscreen phage-induction assay, which quantitatively measures the induction of prophage lambda in Escherichia coli WP2s(lambda), was used to test 14 crude (unfractionated) hazardous industrial waste samples for genotoxic activity in the presence and absence of metabolic activation. Eleven of the 14 wastes induced prophage, and induction was observed at concentrations as low as 0.4 pg per ml. Comparisons between the ability of these waste samples to induce prophage and their mutagenicity in the Salmonella reverse mutation assay indicate that the phage-induction assay detected genotoxic activity in all but one of the wastes that were mutagenic in Salmonella. Moreover, the Microscreen assay detected as genotoxic five additional wastes that were not detected in the Salmonella assay. The applicability of the Microscreen phage-induction assay for screening hazardous wastes for genotoxic activity is discussed, as are some of the problems associated with screening highly toxic wastes containing toxic volatile compounds.

The influence of abiotic factors present in the Rio de la Plata over the chromium genotoxicity

International Nuclear Information System (INIS)

Lopez, L.C.; Moretton, J.

1997-01-01

The alterations suffered by the well-known environmental genotoxic agent, Cr(V I), were studied. Cr(V I) salts were dissolved in water effluent river receptors waters such as from the Rio de la Plata. The influence of abiotic factors present in this kind of water was evaluated using the Rec. assay in Bacillus subtilis. The results detected a soluble fraction that potentiated Cr(V I) genotoxicity. This substance (or group of substances) is sensible to sterilization by heat and UV radiation, and its activity seems to decrease with particulate matter. Its genotoxicity was not affected by high concentrations of particulate matter in the Rio de la Plata water. In samples where chromium salts were added to raw river water, abiotic interference due to sterilization process occurred. A decrease in genotoxicity was found after filtration through inorganic filters (0.22 μ m) and an increase was noticed after exposure to UV radiation. (Author)

Assessment of the in vitro and in vivo genotoxicity of extracts and indole monoterpene alkaloid from the roots of Galianthe thalictroides (Rubiaceae).

Science.gov (United States)

Fernandes, L M; Garcez, W S; Mantovani, M S; Figueiredo, P O; Fernandes, C A; Garcez, F R; Guterres, Z R

2013-09-01

Roots of Galianthe thalictroides K. Schum. (Rubiaceae) are used in folk medicine in the State of Mato Grosso do Sul, Brazil, for treating and preventing cancer. To gain information about the genotoxicity of extracts (aqueous and EtOH), the CHCl₃ phase resulting from partition of the EtOH extract and the indole monoterpene alkaloid 1 obtained from this plant. The genotoxicity of 1 and extracts was evaluated in vivo through the Drosophila melanogaster wing Somatic Mutation and Recombination Test - SMART, while in vitro cytotoxic (MTT) and Comet assays were performed only with alkaloid 1. The results obtained with the SMART test indicated that the aqueous extract had no genotoxic activity. The EtOH extract was not genotoxic to ST descendants but genotoxic to HB ones. The CHCl₃ phase was genotoxic and cytotoxic. Alkaloid 1 showed significant mutational events with SMART, in the cytotoxicity assay (MTT), it showed a high cytotoxicity for human hepatoma cells (HepG2), whereas for the Comet assay, not showing genotoxic activity. The ethanol extract was shown to be genotoxic to HB descendants in the SMART assay, while the results obtained in this test for the monoterpene indole alkaloid 1 isolated from this extract. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

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

Science.gov (United States)

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

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 interference, enables the analysis of turbid samples and allows detection even in small volumes without loss of sensitivity. Based on this understanding, we aim to develop a new umu test system with hydrodynamic chronoamperometry using a rotating disk electrode (RDE) in a microliter droplet. PAPG when used as a substrate is not electroactive at the potential at which PAP is oxidized to p-quinone imine (PQI), so the current response of chronoamperometry resulting from the oxidation of PAP to PQI is directly proportional to the enzymatic activity of S. typhimurium. This was achieved by performing genotoxicity tests for 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide (AF-2) and 2-aminoanthracene (2-AA) as model genotoxic compounds. The results obtained in this study indicated that the signal detection in the genotoxicity assay based on hydrodynamic voltammetry was less influenced by the presence of colored components and sediment particles in the samples when compared to the usual colorimetric signal detection. The influence caused by the presence of humic acids (HAs) and artificial sediment on the genotoxic property of selected model compounds such as 4-nitroquinoline-N-oxide (4-NQO), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), 1,8-dinitropyrene (1,8-DNP) and 1-nitropyrene (1-NP) were also investigated. The results showed that the genotoxicity of 1-NP and MX changed in the presence of 10 mg·L−1 HAs. The genotoxicity of tested chemicals with a high hydrophobicity such as 1,8-DNP

New investigations into the genotoxicity of cobalt compounds and their impact on overall assessment of genotoxic risk.

Science.gov (United States)

Kirkland, David; Brock, Tom; Haddouk, Hasnaà; Hargeaves, Victoria; Lloyd, Melvyn; Mc Garry, Sarah; Proudlock, Raymond; Sarlang, Séverine; Sewald, Katherina; Sire, Guillaume; Sokolowski, Andrea; Ziemann, Christina

2015-10-01

The genotoxicity of cobalt metal and cobalt compounds has been widely studied. Several publications show induction of chromosomal aberrations, micronuclei or DNA damage in mammalian cells in vitro in the absence of S9. Mixed results were seen in gene mutation studies in bacteria and mammalian cells in vitro, and in chromosomal aberration or micronucleus assays in vivo. To resolve these inconsistencies, new studies were performed with soluble and poorly soluble cobalt compounds according to OECD-recommended protocols. Induction of chromosomal damage was confirmed in vitro, but data suggest this may be due to oxidative stress. No biologically significant mutagenic responses were obtained in bacteria, Tk(+/-) or Hprt mutation tests. Negative results were also obtained for chromosomal aberrations (in bone marrow and spermatogonia) and micronuclei at maximum tolerated doses in vivo. Poorly soluble cobalt compounds do not appear to be genotoxic. Soluble compounds do induce some DNA and chromosomal damage in vitro, probably due to reactive oxygen. The absence of chromosome damage in robust GLP studies in vivo suggests that effective protective processes are sufficient to prevent oxidative DNA damage in whole mammals. Overall, there is no evidence of genetic toxicity with relevance for humans of cobalt substances and cobalt metal. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Approaches to the risk assessment of genotoxic carcinogens in food: a critical appraisal.

Science.gov (United States)

O'Brien, J; Renwick, A G; Constable, A; Dybing, E; Müller, D J G; Schlatter, J; Slob, W; Tueting, W; van Benthem, J; Williams, G M; Wolfreys, A

2006-10-01

The present paper examines the particular difficulties presented by low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, and proposes a structured approach for the evaluation of such compounds. While the ALARA approach is widely applicable to all substances in food that are both carcinogenic and genotoxic, it does not take carcinogenic potency into account and, therefore, does not permit prioritisation based on potential risk or concern. In the absence of carcinogenicity dose-response data, an assessment based on comparison with an appropriate threshold of toxicological concern may be possible. When carcinogenicity data from animal bioassays are available, a useful analysis is achieved by the calculation of margins of exposure (MOEs), which can be used to compare animal potency data with human exposure scenarios. Two reference points on the dose-response relationship that can be used for MOE calculation were examined; the T25 value, which is derived from linear extrapolation, and the BMDL10, which is derived from mathematical modelling of the dose-response data. The above approaches were applied to selected food-borne genotoxic carcinogens. The proposed approach is applicable to all substances in food that are DNA-reactive genotoxic carcinogens and enables the formulation of appropriate semi-quantitative advice to risk managers.

Cytotoxic and genotoxic studies of essential oil from Rosa damascene Mill., Kashan, Iran.

Science.gov (United States)

Shokrzadeh, Mohammad; Habibi, Emran; Modanloo, Mona

2017-08-01

Aim Rosa damascene Mill. belongs to the family of Roseaceae and its essential oil is produced in large amounts in Iran. The wide application of rose oil has raised questions about potential adverse health effects. We have investigated cytotoxic activity and genotoxic effects of Rosa oil from Kashan, Iran. Methods The cytotoxic effect and IC50 of the essential oil on the cell lines was studied followed by MTT assay. In this assay mitochondrial oxidoreductase enzymes with reducing the tetrazolium dye MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) reflect the number of viable cells. Genotoxic effect of the oil was evaluated by micronucleus assay by evaluating produced micronuclei due to cytogenetic damage in binucleated lymphocytes. Results The results showed that essential oil significantly had cytotoxic and genotoxic effects at doses over 10µg/mL (pessential oil of Rose showed lower IC50 in cancer cell line (A549) in comparison with the normal cell line (NIH3T3). Conclusion Cytotoxic and genotoxic properties of essential oil of Rose in Kashan, Iran, are safe at a dose of 10µg/mL. Also, a good cytotoxic effect was shown and could be introduced as an anticancer compound. Further studies are needed with regard to anti-cancer effects of Rose essential oil. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

Genotoxic damage in cultured human peripheral blood lymphocytes ...

African Journals Online (AJOL)

Falaq Naz

2012-06-29

Jun 29, 2012 ... Genotoxic damage in cultured human peripheral blood lymphocytes of oral ... catechol estrogens and quinines, via redox reactions causes oxidative damage to .... volume was prepared for each donor. About, 0.8 ml of cell sus .... duce the adverse effects of OCs, such as the reduction in the estrogen content.

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.

Environmental genotoxicity and risk assessment in the Gulf of Riga (Baltic Sea) using fish, bivalves, and crustaceans.

Science.gov (United States)

Butrimavičienė, Laura; Baršienė, Janina; Greiciūnaitė, Janina; Stankevičiūtė, Milda; Valskienė, Roberta

2018-06-21

Environmental genotoxicity in the Gulf of Riga was assessed using different bioindicators (fish, clams, and isopods) collected from 14 study stations. Comparison of genotoxicity responses (micronuclei (MN) and nuclear buds (NB)) in blood erythrocytes of herring (Clupea harengus), eelpout (Zoarces viviparous), and flounder (Platichthys flesus) revealed the species- and site-specific differences. For the first time, the analysis of genotoxicity was carried out in gill cells of isopods Saduria entomon. The highest inductions of MN and NB in gill cells of investigated S. entomon and clams (Macoma balthica) were evaluated in specimens from station 111A (offshore zone). In fish, the highest incidences of MN were measured in eelpout and in herring collected in the southern part of Gulf of Riga (station GOR3/41S). Moreover, in the southern coastal area, the assessment of genotoxicity risk (according to micronuclei levels) indicated exceptionally high risk for flounder, eelpout, and clams.

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

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.

Exposure to sorbitol during lactation causes metabolic alterations and genotoxic effects in rat offspring.

Science.gov (United States)

Cardoso, Felipe S; Araujo-Lima, Carlos F; Aiub, Claudia A F; Felzenszwalb, Israel

2016-10-17

Sorbitol is a polyol used by the food industry as a sweetener. Women are consuming diet and light products containing sorbitol during pregnancy and in the postnatal period to prevent themselves from excessive weight gain and maintain a slim body. Although there is no evidence for the genotoxicity of sorbitol in the perinatal period, this study focused on evaluating the effects of the maternal intake of sorbitol on the biochemical and toxicological parameters of lactating Wistar rat offspring after 14days of mother-to-offspring exposure. A dose-dependent reduction of offspring length was observed. An increase in sorbitol levels determined in the milk was also observed. However, we detected an inverse relationship between the exposition dose in milk fructose and triacylglycerols concentrations. There was an increase in the plasmatic levels of ALT, AST and LDLc and a decrease in proteins, cholesterol and glucose levels in the offspring. Sorbitol exposure caused hepatocyte genotoxicity, including micronuclei induction. Maternal sorbitol intake induced myelotoxicity and myelosuppression in their offspring. The Comet assay of the blood cells detected a dose-dependent genotoxic response within the sorbitol-exposed offspring. According to our results, sorbitol is able to induce important metabolic alterations and genotoxic responses in the exposed offspring. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

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.

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

DEFF Research Database (Denmark)

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

1996-01-01

was further increased to 5.4-fold and 6.6-fold of the control values, respectively (p propylene glycol (5 microliters/g b.wt., twice with a 60-min interval), a selective CYP2E1 inhibitor, reduced the increase in the tail length by about half at all doses in both cell types (p ...The myelotoxic and genotoxic effects of benzene have been related to oxidative DNA damage after metabolism by CYP2E1. Single cell gel electrophoresis (alkaline comet assay) detects DNA damage and may thus be a convenient method for the study of benzene genotoxicity. Benzene exposure to NMRI mice.......01). By comparing our data with those from genotoxicity studies on benzene using other methods, we conclude that the 'alkaline comet assay' is a sensitive method to detect DNA damage induced by benzene. We also infer that CYP2E1 contributes, at least partly, to the formation of the 'comet'-inducing metabolites...

Eco- and genotoxicity profiling of a rapeseed biodiesel using a battery of bioassays.

Science.gov (United States)

Eck-Varanka, Bettina; Kováts, Nora; Horváth, Eszter; Ferincz, Árpád; Kakasi, Balázs; Nagy, Szabolcs Tamás; Imre, Kornélia; Paulovits, Gábor

2018-04-30

Biodiesel is considered an important renewable energy source but still there is some controversy about its environmental toxicity, especially to aquatic life. In our study, the toxicity of water soluble fraction of biodiesel was evaluated in relatively low concentrations using a battery of bioassays: Vibrio fischeri bioluminescence inhibition, Sinapis alba root growth inhibition, Daphnia magna immobilization, boar semen live/dead ratio and DNA fragmentation and Unio pictorum micronucleus test. While the S. alba test indicated nutritive (stimulating) effect of the sample, the biodiesel exerted toxic effect in the aquatic tests. D. magna was the most sensitive with EC 50 value of 0.0226%. For genotoxicity assessment, the mussel micronucleus test (MNT) was applied, detecting considerable genotoxic potential of the biodiesel sample: it elucidated micronuclei formation already at low concentration of 3.3%. Although this test has never been employed in biodiesel eco/genotoxicity assessments, it seems a promising tool, based on its appropriate sensitivity, and representativity. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of Boron Toxicity on Oxidative Stress and Genotoxicity in Wheat (Triticum aestivum L.).

Science.gov (United States)

Çatav, Şükrü Serter; Genç, Tuncer Okan; Kesik Oktay, Müjgan; Küçükakyüz, Köksal

2018-04-01

Boron (B) toxicity, which occurs in semi-arid and arid environments, can adversely affect the growth and yield of many plants. The aim of this study was to determine the effects of different concentrations of boric acid (3, 6, 9 and 12 mM) on growth, oxidative stress and genotoxicity parameters in root and shoot tissues of wheat seedlings. Our results indicate that B stress inhibits root and shoot growth of wheat in a concentration-dependent manner, and leads to increases in TBARS and H 2 O 2 contents in shoot tissue. Moreover, our findings suggest that high concentrations of B may exert a genotoxic effect on wheat. To the best of our knowledge, this is the first report to evaluate the effect of B stress on genotoxicity in both root and shoot tissues of wheat.

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.

Does Caesalpinia bonducella ameliorate genotoxicity? An in vitro ...

African Journals Online (AJOL)

The aim of the study is to investigate the antimutagenic and antigenotoxic potential of alcoholic extracts of C. bonducella against methyl methane sulfonate (MMS) induced genotoxicity. In this experiment we have used in vitro method i.e., human lymphocyte culture and in vivo method in bone marrow cells of albino mice, ...

Genotoxicity and mutagenicity of solid waste leachates: A review

African Journals Online (AJOL)

user

2013-07-03

Jul 3, 2013 ... There is need for a shift from waste disposal to sustainable waste management. Awareness on possible health ... Key words: Solid waste leachate, genotoxicity, mutagenicity, environmental pollution. INTRODUCTION. Solid wastes .... landfills and incineration residues from Japan include persistent organic ...

Genotoxicity of topoisomerase II inhibitors: An anti-infective perspective

International Nuclear Information System (INIS)

Smart, Daniel J.

2008-01-01

At present, an inevitable consequence of a chemical's inhibitory activity on key regulators of DNA topology in bacteria, the type II topoisomerases, is a less pronounced effect on their eukaryotic counterparts. In the context of anti-infectives drug development, this may pose a risk to patient safety as inhibition of eukaryotic type II topoisomerases (TOPO II) can result in the generation of DNA double-strand breaks (DSBs), which have the potential to manifest as mutations, chromosome breakage or cell death. The biological effects of several TOPO II inhibitors in mammalian cells are described herein; their modulation of DSB damage response parameters is examined and evidence for the existence of a threshold concept for genotoxicity and its relevance in safety assessment is discussed. The potential utility of γH2AX, a promising and highly sensitive molecular marker for DSBs, in a novel genotoxicity 'pre-screen' to conventional assays is also highlighted

New investigations into the genotoxicity of cobalt compounds and their impact on overall assessment of genotoxic risk

OpenAIRE

Kirkland, David; Brock, Tom; Haddouk, Hasnaà; Hargeaves, Victoria; Lloyd, Melvyn; Mc Garry, Sarah; Proudlock, Raymond; Sarlang, Séverine; Sewald, Katherina; Sire, Guillaume; Sokolowski, Andrea; Ziemann, Christina

2015-01-01

The genotoxicity of cobalt metal and cobalt compounds has been widely studied. Several publications show induction of chromosomal aberrations, micronuclei or DNA damage in mammalian cells in vitro in the absence of S9. Mixed results were seen in gene mutation studies in bacteria and mammalian cells in vitro, and in chromosomal aberration or micronucleus assays in vivo. To resolve these inconsistencies, new studies were performed with soluble and poorly soluble cobalt compounds according to OE...

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.

Biodetection of potential genotoxic pollutants entering the human food chain through ashes used in livestock diets.

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Sanchez-Vicente, Laura; Herraez, Elisa; Briz, Oscar; Nogales, Rogelio; Molina-Alcaide, Eduarda; Marin, Jose J G

2016-08-15

Ash derived from energy generation is used as a source of minerals in livestock feeds. The microbial biosensor recApr-Luc2 was built to detect genotoxic hazard in recycled ash. Escherichia coli SOS gene (recA, lexA, dinI and umuC) expression in response to cisplatin-induced DNA damage led to the selection of the recA promoter. The biosensor required functional RecA expression to respond to genotoxic heavy metals (Cr>Cd≈Pb), and polluted ash induced a strong recApr-Luc2 response. In human liver and intestinal cells, heavy metals induced acute toxicity (Cr>Cd>Pb) at concentrations sufficient to activate recApr-Luc2. Cytostatic effects, including genotoxicity, were cell- and metal-dependent, apart from Cr. In agreement with the recApr-Luc2 bioassay, Cr had the strongest effect in all cells. In conclusion, recApr-Luc2 could be useful for evaluating the genotoxic risk of pollutants present in ash that might be concentrated in animal products and, thus, entering the human food chain. Copyright © 2016 Elsevier Ltd. All rights reserved.

An evaluation of the genotoxic and cytotoxic effects of the anti-obesity drugs sibutramine and fenproporex.

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da Silva, Cristiano José; dos Santos, José Ernesto; Satie Takahashi, Catarina

2010-03-01

Anti-obesity medications deserve special considerations at the present time due to an increasing number of overweight and obese people who require these therapeutic alternatives. Obesity is positively associated with several chronic illnesses, including cancer. In this work, we evaluated the possible genotoxic and/or cytotoxic actions of two drugs, sibutramine and fenproporex, in the doses of 10, 20 and 40 mg/kg body weight (bw), administered intraperitoneally in male Swiss mice. The genotoxic effect was analyzed by comet assay and micronucleus test. We found that both drugs increased the frequency of genotoxic damage in Swiss mice, but did not present cytotoxic activities towards the polychromatic erythrocytes of the bone marrow of these animals.

Determination of heavy metals and genotoxicity of water from an ...

African Journals Online (AJOL)

Determination of heavy metals and genotoxicity of water from an artesian well ... do Amaral, Vanessa Marques de Oliveira Moraes, Luciana Pereira Silva ... environmental interest because it is the most important zinc producer district of Brazil.

Applicability of in silico genotoxicity models on food and feed ingredients.

Science.gov (United States)

Vuorinen, Anna; Bellion, Phillip; Beilstein, Paul

2017-11-01

Evaluation of the genotoxic potential of food and feed ingredients is required in the development of new substances and for their registration. In addition to in vitro and in vivo assays, in silico tools such as expert alert-based and statistical models can be used for data generation. These in silico models are commonly used among the pharmaceutical industry, whereas the food industry has not widely adopted them. In this study, the applicability of in silico tools for predicting genotoxicity was evaluated, with a focus on bacterial mutagenicity, in vitro and in vivo chromosome damage assays. For this purpose, a test set of 27 food and feed ingredients including vitamins, carotenoids, and nutraceuticals with experimental genotoxicity data was constructed from proprietary data. This dataset was run through multiple models and the model applicability was analyzed. The compounds were generally within the applicability domain of the models and the models predicted the compounds correctly in most of the cases. Although the regulatory acceptance of in silico tools as single data source is still limited, the models are applicable and can be used in the safety evaluation of food and feed ingredients. Copyright © 2017 Elsevier Inc. All rights reserved.

Can Genotoxic Effect be Model Dependent in Allium Test?-An Evidence

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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

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

Directory of Open Access Journals (Sweden)

Huarong Guo

2012-09-01

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

Investigation of potential genotoxic activity using the SOS Chromotest for real paracetamol wastewater and the wastewater treated by the Fenton process.

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Kocak, Emel

2015-01-01

The potential genotoxic activity associated with high strength real paracetamol (PCT) wastewater (COD = 40,000 mg/L, TOC = 12,000 mg/L, BOD5 = 19,320 mg/L) from a large-scale drug-producing plant in the Marmara Region, was investigated in pre- and post- treated wastewater by the Fenton process (COD = 2,920 mg/L, TOC = 880 mg/L; BOD5 = 870 mg/L). The SOS Chromotest, which is based on Escherichia coli PQ37 activities, was used for the assessment of genotoxicity. The corrected induction factors (CIF) values used as quantitative measurements of the genotoxic activity were obtained from a total of four different dilutions (100, 50, 6.25, and 0.078 % v/v.) for two samples, in triplicate, to detect potentially genotoxic activities with the SOS Chromotest. The results of the SOS Chromotest demonstrated CIFmax value of 1.24, indicating that the PCT effluent (non-treated) is genotoxic. The results of the SOS Chromotest showed an CIFmax value of 1.72, indicating that the wastewater treated by Fenton process is genotoxic. The findings of this study clearly reveal that the PCT wastewater (non-treated) samples have a potentially hazardous impact on the aquatic environment before treatment, and in the wastewater that was treated by the Fenton process, genotoxicity generally increased.

Cytotoxicity and genotoxicity property of hydroxyapatite-mullite eluates.

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Kalmodia, Sushma; Sharma, Vyom; Pandey, Alok K; Dhawan, Alok; Basu, Bikramjit

2011-02-01

Long-term biomedical applications of implant materials may cause osteolysis, aseptic losing and toxicity. Therefore, we investigated the cytotoxic and genotoxic potential of hydroxyapatite (HA) mullite eluates in L929 mouse fibroblast cells. The spark plasma sintered HA-20% mullite biocomposite (HA20M) were ground using mortar and pestle as well as ball milling. The cells were exposed for 6 h to varying concentrations (10, 25, 50, 75 and 100%) of the eluates of HA-20% mullite (87 nm), HA (171 nm) and mullite (154 nm). The scanning electron microscopy and MTT assay revealed the concentration dependent toxicity of H20M eluate at and above 50%. The analysis of the DNA damaging potential of HA, mullite and HA20M eluates using Comet assay demonstrated a significant DNA damage by HA20M which was largely related to the presence of mullite. The results collectively demonstrate the cytotoxic and genotoxic potential of HA20M eluate in L929 cells is dependent on particle size, concentration and composition.

THE GENOTOXICITY OF AMBIENT OUTDOOR AIR, A REVIEW: SALMONELLA MUTAGENICITY

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The genotoxicity of ambient outdoor air, a review: Salmonella mutagenicityAbstractMutagens in urban air pollution come from anthropogenic sources (especially combustion sources) and are products of airborne chemical reactions. Bacterial mutation tests have been used ...

In vitro and in vivo genotoxicity assessment of HI-6 dimethanesulfonate/oxime.

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Nakab, Lauren; Bardot, Isabelle; Bardot, Sébastien; Simar, Sophie; Marzin, Daniel; Nesslany, Fabrice

2014-03-01

Organophosphate compounds, which induce organophosphate poisoning, were originally used as pesticides. But this type of product has also been used as warfare nerve agent like sarin, soman, Russian VX, or tabun. HI-6-dimethanesulfonate is a salt of the oxime HI-6 used in the treatment of nerve-agent poisoning. It is known to be the best re-activator component of inactivated acetyl cholinesterase. HI-6-dimethanesulfonate has shown a higher level of solubility with similar potency to reactivate acetyl cholinesterase and a similar pharmacokinetics profile compared with HI-6 dichloride. HI-6 dimethanesulfonate was tested for its mutagenic and genotoxic potential by use of the standard ICH S2R (1) battery for the evaluation of pharmaceuticals. HI-6-dimethanesulfonate was mutagenic in the Ames test only in the presence of metabolic activation. In the mutation assay at the Tk locus in L5178Y mouse-lymphoma cells, HI-6-dimethanesulfonate showed mutagenic activity both with and without metabolic activation, with a significant increase in small colonies. The effects were in favour of a clastogenic activity. It was concluded that the compound was mutagenic and possibly clastogenic in vitro. In contrast, the in vivo micronucleus test in rat bone-marrow did not demonstrate any genotoxic activity and the Comet assay performed in rat liver did not show any statistically or biologically significant increases in DNA strand-breaks. The results of both in vivo studies performed on two different organs with two endpoints are sufficient to conclude the absence of a genotoxic hazard in vivo and to consider that there is no genotoxic concern in humans for HI-6-dimethanesulfonate. Copyright © 2014 Elsevier B.V. All rights reserved.

E2F1 transcription is induced by genotoxic stress through ATM/ATR activation.

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Carcagno, Abel L; Ogara, María F; Sonzogni, Silvina V; Marazita, Mariela C; Sirkin, Pablo F; Ceruti, Julieta M; Cánepa, Eduardo T

2009-05-01

E2F1, a member of the E2F family of transcription factors, plays a critical role in controlling both cell cycle progression and apoptotic cell death in response to DNA damage and oncogene activation. Following genotoxic stresses, E2F1 protein is stabilized by phosphorylation and acetylation driven to its accumulation. The aim of the present work was to examine whether the increase in E2F1 protein levels observed after DNA damage is only a reflection of an increase in E2F1 protein stability or is also the consequence of enhanced transcription of the E2F1 gene. The data presented here demonstrates that UV light and other genotoxics induce the transcription of E2F1 gene in an ATM/ATR dependent manner, which results in increasing E2F1 mRNA and protein levels. After genotoxic stress, transcription of cyclin E, an E2F1 target gene, was significantly induced. This induction was the result of two well-differentiated effects, one of them dependent on de novo protein synthesis and the other on the protein stabilization. Our results strongly support a transcriptional effect of DNA damaging agents on E2F1 expression. The results presented herein uncover a new mechanism involving E2F1 in response to genotoxic stress.

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

OpenAIRE

Martínez Montañez, Mónica Liseth; Meléndez Gélvez, Iván; Quijano Parra, Alfonso

2012-01-01

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 a...

Development of a Transgenic Model to Assess Bioavailable Genotoxicity in Sediments

National Research Council Canada - National Science Library

1999-01-01

This technical note describes the rationale for using transgenic animal models to assess the potential genotoxicity of sediments, the benefits that can be obtained using such models versus currently...

Genotoxic and chemopreventive assessment of Cynara scolymus L. aqueous extract in a human-derived liver cell line.

Science.gov (United States)

da Silva, Regiane Pereira; Jacociunas, Laura Vicedo; de Carli, Raíne Fogliati; de Abreu, Bianca Regina Ribas; Lehmann, Mauricio; da Silva, Juliana; Ferraz, Alexandre de Barros Falcão; Dihl, Rafael Rodrigues

2017-10-01

Cynara scolymus L., popularly known as artichoke, is consumed as food and used as tea infusions for pharmacological purposes to treat liver dysfunctions and other conditions. Scientific data on the safety and protective effect of artichoke in human-derived liver cells is missing. This study investigated the genotoxic and modulatory effect of a liophilized extract suspended in water of C. scolymus L. leaves. Four extract concentrations (0.62, 1.25, 2.5 and 5.0 mg/mL) were evaluated using the comet assay on human hepatocyte cultures, HepG2 cells. Genotoxicity was assessed after two treatment periods, 1 and 24 h. Antigenotoxicity was evaluated against oxidative lesions induced by hydrogen peroxide in pre-, simultaneous and post-treatment protocols. Artichoke leaves aqueous extract induced genotoxic effects in HepG2 cells after 1- and 24-h treatments. In turn, extract concentrations of 0.62, 1.25 and 2.5 mg/mL, exhibited a protective effect in pretreatment, compared to hydrogen peroxide alone. However, in simultaneous and post-treatment protocols, only the lowest concentration reduced the frequency of DNA damage induced by hydrogen peroxide. In addition, in the simultaneous treatment protocol, the highest artichoke extract concentration increased hydrogen peroxide genotoxicity. It can be concluded that artichoke is genotoxic, in vitro, to HepG2 cells, but can also modulate hydrogen peroxide DNA damage.

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

International Nuclear Information System (INIS)

Lacaze, Emilie; Pédelucq, Julie; Fortier, Marlène; Brousseau, Pauline; Auffret, Michel; Budzinski, Hélène; Fournier, Michel

2015-01-01

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

Genotoxicity of the Musi River (Hyderabad, India) investigated with the VITOTOX test.

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Vijayashree, B; Ahuja, Y R; Regniers, L; Rao, V; Verschaeve, L

2005-01-01

The bacterial VITOTOX genotoxicity test was used to screen water samples collected from three different stations along the banks of the river Musi, in Hyderabad, India. Water was collected at three stations that differed from each other in the nature of the surrounding industrial and other activities. A number of different pollutants were also measured in water, soil and air samples. The three stations were found highly polluted and different with regard to the genotoxicity and toxicity of their samples. These results demonstrate the need for further biological studies in this area to generate valuable data on genomic instability, risk assessment of cancer, and to provide avenues for risk management.

Relationship between genotoxicity and oxidative stress induced by mercury on common carp (Cyprinus carpio) tissues.

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García-Medina, Sandra; Galar-Martínez, Marcela; Gómez-Oliván, Leobardo Manuel; Ruiz-Lara, Karina; Islas-Flores, Hariz; Gasca-Pérez, Eloy

2017-11-01

Mercury is one of the most toxic metals in aquatic systems since it is able to induce neurobehavioral disorders as well as renal and gastrointestinal tract damage. The common carp Cyprinus carpio is an important species from both an ecological and economic viewpoint as it is consumed in many countries, the top producers being Mexico, China, India and Japan. The present study aimed to evaluate the relation between Hg-induced oxidative stress and genotoxicity in diverse tissues of C. carpio. Specimens were exposed to 0.01mgHg/L (the maximum permissible limit for aquatic life protection), and lipid peroxidation, protein carbonyl content and the activity of antioxidant enzymes were evaluated at 96h. Micronuclei frequency and DNA damage by comet assay were determined at 12, 24, 48, 72 and 96h. Hg induced oxidative stress and genotoxicity on exposed fish, since inhibition of antioxidant enzymes activity and increases in lipid peroxidation, DNA damage and micronuclei frequency occurred. Blood, gill and liver were more susceptible to oxidative stress, while blood were more sensitive to genotoxicity. In conclusion, Hg at concentrations equal to the maximum permissible limit for aquatic life protection induced oxidative stress and genotoxicity on C. carpio, and these two effects prove to be correlated. Copyright © 2017 Elsevier B.V. All rights reserved.

Genotoxic Effects of Exposure to Gasoline Fumes on Petrol Pump Workers.

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Shaikh, Amrin; Barot, Darshana; Chandel, Divya

2018-04-01

Petrol pump workers are occupationally exposed to gasoline and its fumes consisting of several mutagenic chemicals. To evaluate the genotoxic effects of exposure to gasoline fumes on petrol pump workers. The study groups included 70 petrol pump workers (exposed group) and 70 healthy age-matched individuals with no known exposure (comparison group). Buccal micronucleus cytome assay (BMCyt) was performed to check the genotoxicity caused due to inhalation of gasoline fumes. The frequencies of micronucleated cells, nuclear bud, condensed chromatin cells, karyorrhectic cells, pyknotic cells, and karyolytic cells were significantly higher in the exposed workers compared to the comparison group. Exposure to gasoline fumes is associated with increased frequency of cell abnormalities. This may lead to various health consequences including cancer in those occupationally exposed to gasoline fumes.

Potential genotoxicity of traditional chinese medicinal plants and phytochemicals: an overview.

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Zhou, Jue; Ouedraogo, Moustapha; Qu, Fan; Duez, Pierre

2013-12-01

In the last decades, cases of poisoning due to herbal medicines have occurred in many countries; Chinese herbal medicines (CHMs) are occasionally involved. The experience gained from traditional use is efficient to detect immediate or near-immediate relationship between administration and toxic effects but is quite unlikely to detect medium- to long-term toxicities; thorough investigations of herbal medicines (toxicity assessments, active pharmacovigilance) appear then essential for their safe use. Genotoxicity is an especially insidious toxicity that may result in carcinoma development years after exposure; it can arise from multiple compounds, with or without metabolic activation. The present work reviews traditional CHMs and phytochemicals that have been shown to present a genotoxic hazard. Copyright © 2013 John Wiley & Sons, Ltd.

Quantitative structure-activity relationships for toxicity and genotoxicity of halogenated aliphatic compounds: wing spot test of Drosophila melanogaster.

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Chroust, Karel; Pavlová, Martina; Prokop, Zbynek; Mendel, Jan; Bozková, Katerina; Kubát, Zdenek; Zajícková, Veronika; Damborský, Jiri

2007-02-01

Halogenated aliphatic compounds were evaluated for toxic and genotoxic effects in the somatic mutation and recombination test employing Drosophila melanogaster. The tested chemicals included chlorinated, brominated and iodinated; mono-, di- and tri-substituted; saturated and unsaturated alkanes: 1,2-dibromoethane, 1-bromo-2-chloroethane, 1-iodopropane, 2,3-dichloropropene, 3-bromo-1-propene, epibromohydrin, 2-iodobutane, 3-chloro-2-methylpropene, 1,2,3-trichloropropane, 1,2-dichloroethane, 1,2-dichlorobutane, 1-chloro-2-methylpropane, 1,3-dichloropropane, 1,2-dichloropropane, 2-chloroethymethylether, 1-bromo-2-methylpropane and 1-chloropentane. N-methyl-N-nitrosourea served as the positive and distilled water as the negative control. The set of chemicals for the toxicological testing was selected by the use of statistical experiment design. Group of unsaturated aliphatic hydrocarbons were generally more toxic than saturated analogues. The genotoxic effect was observed with 14 compounds in the wing spot test, while 3 substances did not show any genotoxicity by using the wing spot test at 50% lethal concentration. The highest number of wing spots was observed in genotoxicity assay with 1-bromo-2-chloroethane, 1,2-dichloroethane, 1,2-dibromoethane and 1-iodopropane. Nucleophilic superdelocalizability calculated by quantum mechanics appears to be a good parameter for prediction of both toxicity and genotoxicity effects of halogenated aliphatic compounds.

Effect of a base-catalyzed dechlorination process on the genotoxicity of PCB-contaminated soil

Energy Technology Data Exchange (ETDEWEB)

DeMarini, D.M.; Houk, V.S.; Kornel, A.; Rogers, C.J.

1992-01-01

We evaluated the genotoxicity of dichloromethane (DCM) extracts of PCB-contaminated soil before and after the soil had been treated by a base-catalyzed dechlorination process, which involved heating a mixture of the soil, polyethylene glycol, and sodium hydroxide to 250-350 C. This dechlorination process reduced by over 99% the PCB concentration in the soil, which was initially 2,200 ppm. The DCM extracts of both control and treated soils were not mutagenic in strain TA100 of Salmonella, but they were mutagenic in strain TA98. The base-catalyzed dechlorination process reduced the mutagenic potency of the soil by approximately one-half. The DCM extracts of the soils before and after treatment were equally genotoxic in a prophage-induction assay in E. coli, which detects some chlorinated organic carcinogens that were not detected by the Salmonella mutagenicity assay. These results show that treatment of PCB-contaminated soil by this base-catalyzed dechlorination process did not increase the genotoxicity of the soil.

Acute toxicity and genotoxicity of fermented traditional medicine oyaksungi-san

Directory of Open Access Journals (Sweden)

Hwayong Park

2017-06-01

Conclusion: As a whole, no acute toxicity or genotoxicity were observed in all the assays examined. Therefore, fermented OY is considered to be a safe material that can be used for development of complementary and alternative medicine using bioconversion.

Potential genotoxic effects of melted snow from an urban area revealed by the Allium cepa test.

Science.gov (United States)

Blagojević, Jelena; Stamenković, Gorana; Vujosević, Mladen

2009-09-01

The presence of well-known atmospheric pollutants is regularly screened for in large towns but knowledge about the effects of mixtures of different pollutants and especially their genotoxic potential is largely missing. Since falling snow collects pollutants from the air, melted snow samples could be suitable for evaluating potential genotoxicity. For this purpose the Allium cepa anaphase-telophase test was used to analyse melted snow samples from Belgrade, the capital city of Serbia. Samples of snow were taken at two sites, characterized by differences in pollution intensity, in three successive years. At the more polluted site the analyses showed a very high degree of both toxicity and genotoxicity in the first year of the study corresponding to the effects of the known mutagen used as the positive control. At the other site the situation was much better but not without warning signals. The results showed that standard analyses for the presence of certain contaminants in the air do not give an accurate picture of the possible consequences of urban air pollution because the genotoxic potential remains hidden. The A. cepa test has been demonstrated to be very convenient for evaluation of air pollution through analyses of melted snow samples.

In vivo genotoxicity assessment in rats exposed to Prestige-like oil by inhalation.

Science.gov (United States)

Valdiglesias, Vanessa; Kiliç, Gözde; Costa, Carla; Amor-Carro, Óscar; Mariñas-Pardo, Luis; Ramos-Barbón, David; Méndez, Josefina; Pásaro, Eduardo; Laffon, Blanca

2012-01-01

One of the largest oil spill disasters in recent times was the accident of the oil tanker Prestige in front of the Galician coast in 2002. Thousands of people participated in the cleanup of the contaminated areas, being exposed to a complex mixture of toxic substances. Acute and prolonged respiratory symptoms and genotoxic effects were reported, although environmental exposure measurements were restricted to current determinations, such that attribution of effects observed to oil exposure is difficult to establish. The aim of this study was to analyze peripheral blood leukocytes (PBL) harvested from a rat model of subchronic exposure to a fuel oil with similar characteristics to that spilled by the Prestige tanker, in order to determine potential genotoxic effects under strictly controlled, in vivo exposure. Wistar Han and Brown Norway rats were exposed to the oil for 3 wk, and micronucleus test (MN) and comet assay, standard and modified with 8-oxoguanine DNA glycosylase (OGG1) enzyme, were employed to assess genotoxicity 72 h and 15 d after the last exposure. In addition, the potential effects of oil exposure on DNA repair capacity were determined by means of mutagen sensitivity assay. Results obtained from this study showed that inhalation oil exposure induced DNA damage in both Brown Norway and Wistar Han rats, especially in those animals evaluated 15 d after exposure. Although alterations in the DNA repair responses were noted, the sensitivity to oil substances varied depending on rat strain. Data support previous positive genotoxicity results reported in humans exposed to Prestige oil during cleanup tasks.

Genotoxic effects of environmental endocrine disruptors on the aquatic insect Chironomus riparius evaluated using the comet assay.

Science.gov (United States)

Martínez-Paz, Pedro; Morales, Mónica; Martínez-Guitarte, José Luis; Morcillo, Gloria

2013-12-12

Genotoxicity is one of the most important toxic endpoints in chemical toxicity testing and environmental risk assessment. The aim of this study was to evaluate the genotoxic potential of various environmental pollutants frequently found in aquatic environments and characterized by their endocrine disrupting activity. Monitoring of DNA damage was undertaken after in vivo exposures of the aquatic larvae of the midge Chironomus riparius, a model organism that represents an abundant and ecologically relevant macroinvertebrate, widely used in freshwater toxicology. DNA-induced damage, resulting in DNA fragmentation, was quantified by the comet assay after short (24 h) and long (96 h) exposures to different concentrations of the selected toxicants: bisphenol A (BPA), nonylphenol (NP), pentachlorophenol (PCP), tributyltin (TBT) and triclosan (TCS). All five compounds were found to have genotoxic activity as demonstrated by significant increases in all the comet parameters (%DNA in tail, tail length, tail moment and Olive tail moment) at all tested concentrations. Persistent exposure did not increase the extent of DNA damage, except for TCS at the highest concentration, but generally there was a reduction in DNA damage thought to be associated with the induction of the detoxification processes and repairing mechanisms. Comparative analysis showed differences in the genotoxic potential between the chemicals, as well as significant time and concentration-dependent variations, which most likely reflect differences in the ability to repair DNA damage under the different treatments. The present report demonstrates the sensitivity of the benthic larvae of C. riparius to these environmental genotoxins suggesting its potential as biomonitor organism in freshwater ecosystems. The results obtained about the DNA-damaging potential of these environmental pollutants reinforce the need for additional studies on the genotoxicity of endocrine active substances that, by linking genotoxic

Lack of genotoxicity in medical oncology nurses handling antineoplastic drugs: effect of work environment and protective equipment.

Science.gov (United States)

Gulten, Tuna; Evke, Elif; Ercan, Ilker; Evrensel, Turkkan; Kurt, Ender; Manavoglu, Osman

2011-01-01

In this study we aimed to investigate the genotoxic effects of antineoplastic agents in occupationally exposed oncology nurses. Genotoxic effects mean the disruptive effects in the integrity of DNA and they are associated with cancer development. Biomonitoring of health care workers handling antineoplastic agents is helpful for the evaluation of exposure to cytostatics. The study included an exposed and two control groups. The exposed group (n=9) was comprised of oncology nurses. The first (n=9) and second (n=10) control groups were comprised of subjects who did not come into contact with antineoplastic drugs working respectively in the same department with oncology nurses and in different departments. Genotoxicity evaluation was performed using SCE analysis. After applying culture, harvest and chromosome staining procedures, a total of 25 metaphases were analyzed per person. Kruskal Wallis test was used to perform statistical analysis. A statistically significant difference of sister chromatid exchange frequencies was not observed between the exposed and control groups. Lack of genotoxicity in medical oncology nurses might be due to good working conditions with high standards of technical equipment and improved personal protection.

Titanium dioxide nanoparticles cause genotoxicity in human lung epithelial cells

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The use of engineered nanoparticles in consumer products is steadily increasing. However, the health effects of exposure to these nanoparticles are not thoroughly understood. This study investigated the genotoxicity of six titanium dioxide and two cerium oxide nanoparticles of va...

Outcomes of colon resection in patients with metastatic colon cancer.

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Moghadamyeghaneh, Zhobin; Hanna, Mark H; Hwang, Grace; Mills, Steven; Pigazzi, Alessio; Stamos, Michael J; Carmichael, Joseph C

2016-08-01

Patients with advanced colorectal cancer have a high incidence of postoperative complications. We sought to identify outcomes of patients who underwent resection for colon cancer by cancer stage. The National Surgical Quality Improvement Program database was used to evaluate all patients who underwent colon resection with a diagnosis of colon cancer from 2012 to 2014. Multivariate logistic regression analysis was performed to investigate patient outcomes by cancer stage. A total of 7,786 colon cancer patients who underwent colon resection were identified. Of these, 10.8% had metastasis at the time of operation. Patients with metastatic disease had significantly increased risks of perioperative morbidity (adjusted odds ratio [AOR]: 1.44, P = .01) and mortality (AOR: 3.72, P = .01). Patients with metastatic disease were significantly younger (AOR: .99, P colon cancer have metastatic disease. Postoperative morbidity and mortality are significantly higher than in patients with localized disease. Published by Elsevier Inc.

Antegrade Colonic Lavage in Acute Colonic Obstruction

OpenAIRE

Foster, Michael E.; Johnson, Colin D.

1986-01-01

Conventional management of acute left sided colonic obstruction employs some form of proximal colostomy. Intraoperative antegrade colonic irrigation relieves proximal faecal loading and may permit safer primary resection and anastomosis. The results of a pilot study are presented, and are shown to be favourable.

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

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Soriano-Carot María

2012-02-01

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

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

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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.

Detection of genotoxic effects of drinking water disinfection by-products using Vicia faba bioassay.

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Hu, Yu; Tan, Li; Zhang, Shao-Hui; Zuo, Yu-Ting; Han, Xue; Liu, Na; Lu, Wen-Qing; Liu, Ai-Lin

2017-01-01

Plant-based bioassays have gained wide use among the toxicological and/or ecotoxicological assessment procedures because of their simplicity, sensitivity, low cost, and reliability. The present study describes the use of Vicia faba (V. faba) micronucleus (MN) test and V. faba comet assay in the evaluation of the genotoxic potential of disinfection by-products (DBPs) commonly found in chlorine-disinfected drinking water. Five haloacetic acids and three halogenated acetonitriles were chosen as representatives of DBPs in this study because they are of potentially great public health risk. Results of the MN test indicated that monochloroacetic acid (MCA), monobromoacetic acid (MBA), dichloroacetic acid (DCA), dibromoacetic acid (DBA), trichloroacetic acid (TCA), and trichloroacetonitrile (TCAN) caused a statistically significant increase in MN frequency in V. faba root tip cells. However, no genotoxic response was observed for dichloroacetonitrile (DCAN) and dibromoacetonitrile (DBAN). Results of the comet assay showed that all tested DBPs induced a statistically significant increase in genomic DNA damage to V. faba root tip cells. On considering the capacity to detect genomic damage of a different nature, we suggest that a combination of V. faba MN test and V. faba comet assay is a useful tool for the detection of genotoxic effects of DBPs. It is worthy of assessing the feasibility of using V. faba comet assay combined with V. faba MN test to screen for the genotoxic activity of chlorinated drinking water in future work.

Genotoxicity of Nicotiana tabacum leaves on Helix aspersa.

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da Silva, Fernanda R; Erdtmann, Bernardo; Dalpiaz, Tiago; Nunes, Emilene; Ferraz, Alexandre; Martins, Tales L C; Dias, Johny F; da Rosa, Darlan P; Porawskie, Marilene; Bona, Silvia; da Silva, Juliana

2013-07-01

Tobacco farmers are routinely exposed to complex mixtures of inorganic and organic chemicals present in tobacco leaves. In this study, we examined the genotoxicity of tobacco leaves in the snail Helix aspersa as a measure of the risk to human health. DNA damage was evaluated using the micronucleus test and the Comet assay and the concentration of cytochrome P450 enzymes was estimated. Two groups of snails were studied: one fed on tobacco leaves and one fed on lettuce (Lactuca sativa L) leaves (control group). All of the snails received leaves (tobacco and lettuce leaves were the only food provided) and water ad libitum. Hemolymph cells were collected after 0, 24, 48 and 72 h. The Comet assay and micronucleus test showed that exposure to tobacco leaves for different periods of time caused significant DNA damage. Inhibition of cytochrome P450 enzymes occurred only in the tobacco group. Chemical analysis indicated the presence of the alkaloid nicotine, coumarins, saponins, flavonoids and various metals. These results show that tobacco leaves are genotoxic in H. aspersa and inhibit cytochrome P450 activity, probably through the action of the complex chemical mixture present in the plant.

Genotoxicity of Nicotiana tabacum leaves on Helix aspersa

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Fernanda R. da Silva

2013-01-01

Full Text Available Tobacco farmers are routinely exposed to complex mixtures of inorganic and organic chemicals present in tobacco leaves. In this study, we examined the genotoxicity of tobacco leaves in the snail Helix aspersa as a measure of the risk to human health. DNA damage was evaluated using the micronucleus test and the Comet assay and the concentration of cytochrome P450 enzymes was estimated. Two groups of snails were studied: one fed on tobacco leaves and one fed on lettuce (Lactuca sativa L leaves (control group. All of the snails received leaves (tobacco and lettuce leaves were the only food provided and water ad libitum. Hemolymph cells were collected after 0, 24, 48 and 72 h. The Comet assay and micronucleus test showed that exposure to tobacco leaves for different periods of time caused significant DNA damage. Inhibition of cytochrome P450 enzymes occurred only in the tobacco group. Chemical analysis indicated the presence of the alkaloid nicotine, coumarins, saponins, flavonoids and various metals. These results show that tobacco leaves are genotoxic in H. aspersa and inhibit cytochrome P450 activity, probably through the action of the complex chemical mixture present in the plant.

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...

Genotoxic Effects of Exposure to Gasoline Fumes on Petrol Pump Workers

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Amrin Shaikh

2018-04-01

Full Text Available Background: Petrol pump workers are occupationally exposed to gasoline and its fumes consisting of several mutagenic chemicals. Objective: To evaluate the genotoxic effects of exposure to gasoline fumes on petrol pump workers. Methods: The study groups included 70 petrol pump workers (exposed group and 70 healthy age-matched individuals with no known exposure (comparison group. Buccal micronucleus cytome assay (BMCyt was performed to check the genotoxicity caused due to inhalation of gasoline fumes. Results: The frequencies of micronucleated cells, nuclear bud, condensed chromatin cells, karyorrhectic cells, pyknotic cells, and karyolytic cells were significantly higher in the exposed workers compared to the comparison group. Conclusion: Exposure to gasoline fumes is associated with increased frequency of cell abnormalities. This may lead to various health consequences including cancer in those occupationally exposed to gasoline fumes.

ROS-mediated genotoxicity of asbestos-cement in mammalian lung cells in vitro

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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.

Genotoxicity and mutagenicity of Echinodorus macrophyllus (chapéu-de-couro extracts

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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.

Evaluation of river water genotoxicity using the piscine micronucleus test.

Science.gov (United States)

Ergene, Serap; Cavaş, Tolga; Celik, Ayla; Köleli, Nurcan; Aymak, Cemil

2007-07-01

The Berdan River, which empties into the Mediterranean Sea on the east coast of Turkey, receives discharges of industrial and municipal waste. In the present study, the in vivo piscine micronucleus (MN) test was used to evaluate the genotoxicity of water samples collected from different locations along the Berdan River. Nile tilapia (Oreochromis niloticus) were exposed in the laboratory for 2, 4, and 6 days, and micronuclei were evaluated in peripheral blood erythrocytes, gill cells, and caudal fin epithelial cells. A single dose of 5 mg/L cyclophosphamide was used as a positive control. In addition to micronuclei, nuclear abnormalities (NAs), such as binucleated cells and blebbed, notched, and lobed nuclei, were assessed in the erythrocytes, and chemical analyses were carried out to determine the amount of heavy metals in the water samples. MN and NA frequencies were significantly elevated (up to 2- to 3-fold) in fish exposed to river water samples taken downstream of potential discharges, and the elevated responses in gill and fin cells were related to the concentration of heavy metals in the water. MN frequencies (expressed as micronucleated cells/1,000 cells), in both treated and untreated fish, were greatest in gill cells (range: 0.80-3.70), and generally lower in erythrocytes (range: 0.50-2.80), and fin cells (range: 0.45-1.70). The results of this study indicate that the Berdan River is contaminated with genotoxic pollutants and that the genotoxicity is related to the discharge of wastes into the river water.

Protective effect of thymoquinone against diazinon-induced hematotoxicity, genotoxicity and immunotoxicity in rats.

Science.gov (United States)

Danaei, Gholam Hassan; Karami, Mohammad

2017-10-01

Several studies have shown that oxidative stress and cell damage can occur in the very early stages of diazinon (DZN) exposure. The present study was designed to determine the beneficial effect of thymoquinone (Thy), the main component of Nigella sativa (black seed or black cumin) against DZN immunotoxicity, hematotoxicity and genotoxicity in rats. In the present experimental study, 48 male Wistar rats were randomly divided into six groups, (eight per group) as follows: control (receiving corn oil as the DZN solvent), DZN (20mg/kg), Thy (10mg/kg), Thy (2.5mg/kg)+DZN, Thy (5mg/kg)+DZN and Thy (10mg/kg)+DZN. After four weeks of treatment, the hematological parameters of red blood cells (RBCs), white blood cells (WBCs), hemoglobin (Hb), hematocrit (Hct) and platelets (PLTs) were evaluated. The evaluation of genotoxicity was carried out using the micronucleus assay. For measurement of cytokine production, interferon gamma (IFN-γ), interleukin 10 (IL10) and interleukin 4 (IL4) were chosen as immunotoxicity indicators of DZN toxicity. DZN was found to decrease RBCs, WBCs, Hb, Hct, PLTs, butyrl- and acetyl-cholinesterase activity and I FN-γ and increased the micronucleus indices of IL10 and IL4 as compared with the control group. Treatment with Thy reduced DZN hematotoxicity and immunotoxicity, but, significantly, did not prevent genotoxicity. This study showed that Thy (without the significant effect on genotoxicity) decreased the hematological toxicity, immunotoxicity and butyrl and acetyl cholinesterase activity induced by DZN. The success of Thy supplementation against DZN toxicity can be attributed to the antioxidant effects of its constituents. Copyright © 2017. Published by Elsevier B.V.

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

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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.

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

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Soto-García, Marcela; Rosales-Castro, Martha; Escalona-Cardoso, Gerardo N.

2016-01-01

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. PMID:27867402

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.

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

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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.

Formation and removal of genotoxic activity during UV/H

NARCIS (Netherlands)

Heringa, M.B.; Harmsen, D.J.H.; Beerendonk, E.F.; Reus, A.A.; Krul, C.A.M.; Metz, D.H.; Ijpelaar, G.F.

2011-01-01

The objective of this study was to determine the genotoxic activity of water after UV/H₂O₂ oxidation and GAC filtration. Pre-treated surface water from three locations was treated with UV/H₂O₂ with medium pressure (MP) lamps and passed through granulated

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.

Synergistic effect of Gentiana lutea L. on methyl methanesulfonate genotoxicity in the Drosophila wing spot test.

Science.gov (United States)

Patenković, Aleksandra; Stamenković-Radak, Marina; Nikolić, Dragana; Marković, Tamara; Anđelković, Marko

2013-03-27

Gentiana lutea L., the yellow gentian, is herb known for its pharmacological properties, with a long tradition of use for the treatment of a variety of diseases including the use as a remedy for digestion, also in food products and in bitter beverages. The aim of the present study is to evaluate, for the first time, genotoxicity of gentian alone, and its antigenotoxicity against methyl methanesulfonate (MMS). The water infusion of the underground part of gentian were evaluated in vivo using the Drosophila wing spot test, at the dose commonly used in traditional medicine. For antigenotoxic study two types of treatment with gentian and MMS were performed: chronic co-treatment, as well as post-treatment with gentian after acute exposure with MMS. Water infusion of gentian alone did not exhibit genotoxicity. The results of co- and post-treatment experiments with gentian show that gentian enhanced the frequency of mutant clones over the values obtained with MMS alone, instead of reducing the genotoxicity of MMS, for 22.64% and 27.13% respectively. This result suggests a synergism of gentian with MMS, and indicates that water infusion of gentian used in traditional medicine may have particular effects with regard to genotoxicity indicating careful use. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

International Nuclear Information System (INIS)

Cebulska-Wasilewska, A.

1999-01-01

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

Comparative Genotoxicity of Cadmium and Lead in Earthworm Coelomocytes

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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.

A review of the genotoxicity of trimethylolpropane triacrylate (TMPTA).

Science.gov (United States)

Kirkland, David; Fowler, Paul

2018-04-01

Trimethylolpropane triacrylate (TMPTA) is a trifunctional acrylate monomer which polymerizes rapidly when exposed to sources of free radicals. It is widely used as a reactive diluent and polymer building block in the formulation of overprint varnishes, inks and a variety of wood, plastic and metal coatings. TMPTA has been tested in a range of in vitro and in vivo genotoxicity tests. There is no clear evidence of induction of gene mutations by TMPTA in bacteria or mammalian cells in vitro, but there is evidence of clastogenicity from induction of small colony tk mutants in the mouse lymphoma assay, and also induction of micronuclei and chromosomal aberrations. However, TMPTA was negative in bone marrow or blood micronucleus tests in vivo following oral or repeated dermal application, and did not induce comets in bone marrow or liver of mice following intravenous administration, which would have achieved plasma (and therefore tissue) concentrations estimated to exceed those inducing clastogenic effects in vitro. It is concluded that TMPTA is not genotoxic in vivo. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

A study of the colonic transit function by dual radionuclide colon scintigraphy

International Nuclear Information System (INIS)

Yang Weidong; Sun Buzhou; Song Changyi; Lu Jinyan; Wang Shejiao; Zheng Xianghong; Huang Lin; Lei Yamei

1999-01-01

Objective: To establish a new, simple and noninvasive method which can quantitatively analyze the colonic transit function by dual radionuclide colon scintigraphy. Methods: 24 patients with constipation and 32 normal controls were studied. Na 131 I was sealed into capsule made by polyvinylchloride which can not be digested and absorbed in gastrointestinal tract. Patients and normal volunteers swallow 131 I capsules and drink 99 Tc m labelled sulfur colloid solution at the same time. The static image was acquired at the regular time, then calculate the Geometric Center values (GC). Results: 1) The capsules can be clearly located through the colonic contour shown by 99 Tc m labeled sulfur colloid when it reached the large bowel. 2) The transiting time from mouth to cecum, through colon and through whole gastrointestinal in normal people were (6.61 +- 1.94), (36.61 +- 10.51) and (42.72 +- 10.02) h, respectively, in constipation group were (8.03 +- 3.63), (65.50 +- 28.40) and (74.05 +- 28.17) h, respectively. There was no significant difference (P > 0.05) in two groups compared with each other. But the transiting time through colon and whole gastrointestinal in constipation was slower than that in normal people, with significant difference (P < 0.01). 3) Through examination the colonic transit abnormality can be divided into three patterns: whole colon transit delay, right-colon transit delay and left-colon transit delay. Conclusions: This method is a simple, physiologic and quantitative in evaluating the colonic transit, it can also stage the colonic dyskinesia of the patients

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

International Nuclear Information System (INIS)

Tavares, Priscila; Balbinot, Fernanda; Martins de Oliveira, Hugo; Elibio Fagundes, Gabriela; Venâncio, Mireli; Vieira Ronconi, João Vitor; Merlini, Aline; Streck, Emílio L.; Marques da Silva, Paula; Moraes de Andrade, Vanessa

2012-01-01

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.

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.

Comparative Cytotoxicity and Genotoxicity of Particulate and Soluble Hexavalent Chromium in Human and Sperm Whale (Physeter macrocephalus) Skin Cells

Science.gov (United States)

Li Chen, Tânia; LaCerte, Carolyne; Wise, Sandra S.; Holmes, Amie; Martino, Julieta; Wise, John Pierce; Thompson, W. Douglas; Wise, John Pierce

2014-01-01

Chromium (Cr) is a global marine pollutant, present in marine mammal tissues. Hexavalent chromium [Cr(VI)] is a known human carcinogen. In this study we compare the cytotoxic and clastogenic effects of Cr(VI) in human (Homo sapiens) and sperm whale (Physeter macrocephalus) skin fibroblasts. Our data show that increasing concentrations of both particulate and soluble Cr(VI) induce increasing amounts of cytotoxicity and clastogenicity in human and sperm whale skin cells. Furthermore, the data show that sperm whale cells are resistant to these effects exhibiting less cytotoxicity and genotoxicity than the human cells. Differences in Cr uptake accounted for some but not all of the differences in particulate and soluble Cr(VI) genotoxicity, although it did explain the differences in particulate Cr(VI) cytotoxicity. Altogether the data indicate that Cr(VI) is a genotoxic threat to whales, but also suggest that whales have evolved cellular mechanisms to protect them against the genotoxicity of environmental agents such as Cr(VI). PMID:21466859

Genotoxicity studies of organically grown broccoli (Brassica oleracea var. italica) and its interactions with urethane, methyl methanesulfonate and 4-nitroquinoline-1-oxide genotoxicity in the wing spot test of Drosophila melanogaster.

Science.gov (United States)

Heres-Pulido, María Eugenia; Dueñas-García, Irma; Castañeda-Partida, Laura; Santos-Cruz, Luis Felipe; Vega-Contreras, Viridiana; Rebollar-Vega, Rosa; Gómez-Luna, Juan Carlos; Durán-Díaz, Angel

2010-01-01

Broccoli (Brassica oleracea var. italica) has been defined as a cancer preventive food. Nevertheless, broccoli contains potentially genotoxic compounds as well. We performed the wing spot test of Drosophila melanogaster in treatments with organically grown broccoli (OGB) and co-treatments with the promutagen urethane (URE), the direct alkylating agent methyl methanesulfonate (MMS) and the carcinogen 4-nitroquinoline-1-oxide (4-NQO) in the standard (ST) and high bioactivation (HB) crosses with inducible and high levels of cytochrome P450s (CYPs), respectively. Larvae of both crosses were chronically fed with OGB or fresh market broccoli (FMB) as a non-organically grown control, added with solvents or mutagens solutions. In both crosses, the OGB added with Tween-ethanol yielded the expected reduction in the genotoxicity spontaneous rate. OGB co-treatments did not affect the URE effect, MMS showed synergy and 4-NQO damage was modulated in both crosses. In contrast, FMB controls produced damage increase; co-treatments modulated URE genotoxicity, diminished MMS damage, and did not change the 4-NQO damage. The high dietary consumption of both types of broccoli and its protective effects in D. melanogaster are discussed. Copyright 2009 Elsevier Ltd. All rights reserved.

Protective Effect of Melatonin Against Mitomycin C-Induced Genotoxic Damage in Peripheral Blood of Rats

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S. Ortega-Gutiérrez

2009-01-01

Full Text Available Mitomycin C (MMC generates free radicals when metabolized. We investigated the effect of melatonin against MMC-induced genotoxicity in polychromatic erythrocytes and MMC-induced lipid peroxidation in brain and liver homogenates. Rats (N = 36 were classified into 4 groups: control, melatonin, MMC, and MMC + melatonin. Melatonin and MMC doses of 10 mg/kg and 2 mg/kg, respectively, were injected intraperitoneally. Peripheral blood samples were collected at 0, 24, 48, 72, and 96 hours posttreatment and homogenates were obtained at 96 hours posttreatment. The number of micronucleated polychromatic erythrocytes (MN-PCE per 1000 PCE was used as a genotoxic marker. Malondialdehyde (MDA plus 4-hydroxyalkenal (4-HDA levels were used as an index of lipid peroxidation. The MMC group showed a significant increase in MN-PCE at 24, 48, 72, and 96 hours that was significantly reduced with melatonin begin coadministrated. No significant differences were found in lipid peroxidation. Our results indicate that MMC-induced genotoxicity can be reduced by melatonin.

Colon interposition

International Nuclear Information System (INIS)

Isolauri, J.; Tampere Univ. Central Hospital; Paakkala, T.; Arajaervi, P.; Markkula, H.

1987-01-01

Colon interposition was carried out in 12 patients with oesophageal carcinoma and on 38 patients with benign oesophageal disease an average of 71 months before the radiographic examination. Various ischaemic changes including 'jejunization', loss of haustration and stricture formation were observed in 15 cases. In 12 patients one or several diverticula were seen in the colon graft. Reflux was observed in 17 cases in supine position. Double contrast technique in the examination of interposed colon is recommended. (orig.)

The current limitations of in vitro genotoxicity testing and their relevance to the in vivo situation.

Science.gov (United States)

Nesslany, Fabrice

2017-08-01

The standard regulatory core battery of genotoxicity tests generally includes 2 or 3 validated tests with at least one in vitro test in bacteria and one in vitro test on cell cultures. However, limitations in in vitro genotoxicity testing may exist at many levels. The knowledge of the underlying mechanisms of genotoxicity is particularly useful to assess the level of relevance for the in vivo situation. In order to avoid wrong conclusions regarding the actual genotoxicity status of any test substance, it appears very important to be aware of the various origins of related bias leading to 'false positives and negatives' by using in vitro methods. Among these, mention may be made on the metabolic activation system, experimental (extreme) conditions, specificities of the test systems implemented, cell type used etc. The knowledge of the actual 'limits' of the in vitro test systems used is clearly an advantage and may contribute to avoid some pitfalls in order to better assess the level of relevance for the in vivo situation. Copyright © 2016. Published by Elsevier Ltd.

Comparative DNA adduct formation and induction of colonic aberrant crypt foci in mice exposed to 2-amino-9H-pyrido[2,3-b]indole, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline and azoxymethane

Science.gov (United States)

Kim, Sangyub; Guo, Jingshu; O’Sullivan, M. Gerald; Gallaher, Daniel D.; Turesky, Robert J.

2015-01-01

Considerable evidence suggests that environmental factors, including diet and cigarette smoke, are involved in the pathogenesis of colon cancer. Carcinogenic nitroso compounds (NOC), such as N-nitrosodimethylamine (NDMA), are present in tobacco and processed red meat, and NOC have been implicated in colon cancer. Azoxymethane (AOM), commonly used for experimental colon carcinogenesis, is an isomer of NDMA, and it produces the same DNA adducts as does NDMA. Heterocyclic aromatic amines (HAAs) formed during the combustion of tobacco and high-temperature cooking of meats are also associated with an elevated risk of colon cancer. The most abundant carcinogenic HAA formed in tobacco smoke is 2-amino-9H-pyrido[2,3-b]indole (AαC), whereas 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) is the most potent carcinogenic HAA formed during the cooking of meat and fish. However, the comparative tumor-initiating potential of AαC, MeIQ, and AOM is unknown. In this report, we evaluate the formation of DNA adducts as a measure of genotoxicity, and the induction of colonic aberrant crypt foci (ACF) and dysplastic ACF, as an early measure of carcinogenic potency of these compounds in the colon of male A/J mice. Both AαC and AOM induced a greater number of DNA adducts than MeIQ in the liver and colon. AOM induced a greater number of ACF and dysplastic ACF than either AαC or MeIQ. Conversely, based on adduct levels, MeIQ-DNA adducts were more potent than AαC- and AOM-DNA adducts at inducing ACF. Long-term feeding studies are required to relate levels of DNA adducts, induction of ACF, and colon cancer by these colon genotoxicants. PMID:26734915

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.

Chemical fate and genotoxic risk associated with hypochlorite treatment of nicotine

International Nuclear Information System (INIS)

Zarrelli, Armando; DellaGreca, Marina; Parolisi, Alice; Iesce, Maria Rosaria; Cermola, Flavio; Temussi, Fabio; Isidori, Marina; Lavorgna, Margherita; Passananti, Monica; Previtera, Lucio

2012-01-01

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 1 H and 13 C NMR spectroscopy. Preliminary genotoxic SOS Chromotests with Escherichia coli PQ37 evidence no toxicity of the products. - Highlights: ► Processes of chlorination in the treatment of raw water. ► STP chlorination of nicotine. ► Genotoxic evaluation of main degradation products of nicotine.

Hexavalent chromium is cytotoxic and genotoxic to American alligator cells.

Science.gov (United States)

Wise, Sandra S; Wise, Catherine; Xie, Hong; Guillette, Louis J; Zhu, Cairong; Wise, John Pierce; Wise, John Pierce

2016-02-01

Metals are a common pollutant in the aquatic ecosystem. With global climate change, these levels are anticipated to rise as lower pH levels allow sediment bound metals to be released. The American alligator (Alligator mississippiensis) is an apex predator in the aquatic ecosystem and is considered a keystone species; as such it serves as a suitable monitor for localized pollution. One metal of increasing concern is hexavalent chromium (Cr(VI)). It is present in the aquatic environment and is a known human carcinogen and reproductive toxicant. We measured the cytotoxicity and genotoxicity of Cr(VI) in American alligator cells derived from scute tissue. We found that particulate and soluble Cr(VI) are both cytotoxic and genotoxic to alligator cells in a concentration-dependent manner. These data suggest that alligators may be used as a model for assessing the effects of environmental Cr(VI) contamination as well as for other metals of concern. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Analyzing the Genotoxicity of Retroviral Vectors in Hematopoietic Cell Gene Therapy

Directory of Open Access Journals (Sweden)

Luca Biasco

2018-03-01

Full Text Available Retroviral vectors, including those derived from gammaretroviruses and lentiviruses, have found their way into the clinical arena and demonstrated remarkable efficacy for the treatment of immunodeficiencies, leukodystrophies, and globinopathies. Despite these successes, gene therapy unfortunately also has had to face severe adverse events in the form of leukemias and myelodysplastic syndromes, related to the semi-random vector integration into the host cell genome that caused deregulation of neighboring proto-oncogenes. Although improvements in vector design clearly lowered the risk of this insertional mutagenesis, analysis of potential genotoxicity and the consequences of vector integration remain important parameters for basic and translational research and most importantly for the clinic. Here, we review current assays to analyze biodistribution and genotoxicity in the pre-clinical setting and describe tools to monitor vector integration sites in vector-treated patients as a biosafety readout.

Ecotoxicity and genotoxicity of cyclophosphamide, ifosfamide, their metabolites/transformation products and their mixtures

International Nuclear Information System (INIS)

Česen, Marjeta; Eleršek, Tina; Novak, Matjaž; Žegura, Bojana; Kosjek, Tina; Filipič, Metka; Heath, Ester

2016-01-01

Cyclophosphamide (CP) and ifosfamide (IF) are commonly used cytostatic drugs that repress cell division by interaction with DNA. The present study investigates the ecotoxicity and genotoxicity of CP, IF, their human metabolites/transformation products (TPs) carboxy-cyclophosphamide (CPCOOH), keto-cyclophosphamide (ketoCP) and N-dechloroethyl-cyclophosphamide (NdCP) as individual compounds and as mixture. The two parent compounds (CP and IF), at concentrations up to 320 mg L −1 , were non-toxic towards the alga Pseudokirchneriella subcapitata and cyanobacterium Synecococcus leopoliensis. Further ecotoxicity studies of metabolites/TPs and a mixture of parent compounds and metabolites/TPs performed in cyanobacteria S. leopoliensis, showed that only CPCOOH (EC 50  = 17.1 mg L −1 ) was toxic. The measured toxicity (EC 50  = 11.5 mg L −1 ) of the mixture was lower from the toxicity predicted by concentration addition model (EC 50  = 21.1 mg L −1 ) indicating potentiating effects of the CPCOOH toxicity. The SOS/umuC assay with Salmonella typhimurium revealed genotoxic activity of CP, CPCOOH and the mixture in the presence of S9 metabolic activation. Only CPCOOH was genotoxic also in the absence of metabolic activation indicating that this compound is a direct acting genotoxin. This finding is of particular importance as in the environment such compounds can directly affect DNA of non-target organisms and also explains toxicity of CPCOOH against cyanobacteria S. leopoliensis. The degradation study with UV irradiation of samples containing CP and IF showed efficient degradation of both compounds and remained non-toxic towards S. leopoliensis, suggesting that no stable TPs with adverse effects were formed. To our knowledge, this is the first study describing the ecotoxicity and genotoxicity of the commonly used cytostatics CP and IF, their known metabolites/TPs and their mixture. The results indicate the importance of toxicological evaluation and

Cyto-genotoxic and DNA methylation changes induced by different crystal phases of TiO{sub 2}-np in bronchial epithelial (16-HBE) cells

Energy Technology Data Exchange (ETDEWEB)

Ghosh, Manosij, E-mail: gmanosij@gmail.com [K.U.Leuven, Department of Public Health and Primary Care, Centre Environment & Health, B-3000 Leuven (Belgium); Öner, Deniz; Duca, Radu-Corneliu [K.U.Leuven, Department of Public Health and Primary Care, Centre Environment & Health, B-3000 Leuven (Belgium); Cokic, Stevan M. [Department of Oral Health Sciences, KU Leuven BIOMAT, 3000 Leuven (Belgium); Seys, Sven [K.U.Leuven, Department of Immunology and Microbiology, Leuven (Belgium); Kerkhofs, Stef [Centre for Surface Chemistry and Catalysis, KU Leuven, Celestijnenlaan 200f, Heverlee, Leuven (Belgium); Van Landuyt, Kirsten [Department of Oral Health Sciences, KU Leuven BIOMAT, 3000 Leuven (Belgium); Hoet, Peter [K.U.Leuven, Department of Public Health and Primary Care, Centre Environment & Health, B-3000 Leuven (Belgium); Godderis, Lode, E-mail: lode.godderis@med.kuleuven.be [K.U.Leuven, Department of Public Health and Primary Care, Centre Environment & Health, B-3000 Leuven (Belgium); Idewe, External Service for Prevention and Protection at Work, B-3001, Heverlee (Belgium)

2017-02-15

Highlights: • Comet and micronucleus (with and without CytB) assays revealed significant genotoxic effect of TiO{sub 2}-np. • TiO{sub 2}-np induces cell cycle arrest in the S-phase. • Anatase form induces more cyto-genotoxic effect compared to rutile and anatase-rutile mixture. • Significant hypomethylation were observed at for anatase, rutile and anatase: rutile mixture. - Abstract: With the increase in use of TiO{sub 2}-np, a better understanding of their safety is important. In the present study the effect of different crystal phases of TiO{sub 2}-np (anatase, rutile and anatase: rutile mixture; 20–26 nm) were studied for cyto-genotoxicity and global DNA methylation and hydroxymethylation. Cytotoxic response was observed at a concentration of 25 μg/ml for the particles tested. Results of comet and micronucleus (with and without CytB) assays revealed significant genotoxic effect of these particles. Flow cytometry revealed cell cycle arrest in the S-phase. Based on the results, toxicity of the particles could be correlated with their physico-chemical properties (i.e. smaller size and hydrodynamic diameter and larger surface area), anatase form being the most toxic. From the results of the cyto-genotoxicity assays, concentrations were determined for the epigenetic study. Effect on global DNA methylation and hydroxymethylation levels were studied at cyto-genotoxic (25 μg/ml), genotoxic (12.5 μg/ml) and sub cyto-genotoxic (3.25 μg/ml) concentrations using LC–MS/MS analysis. Though no significant changes were observed for 3 h treatment schedule; significant hypomethylation were observed at 24 h for anatase (significant at 3.25 and 25 μg/ml), rutile (significant at 3.25 and 25 μg/ml) and anatase: rutile mixture (significant at 25 μg/ml) forms. The results suggest that epigenetic changes could occur at sub cyto-genotoxic concentrations. And hence for complete characterization of nanoparticle toxicity, epigenetic studies should be performed along with

Evaluation of genotoxic effects of surface waters using a battery of bioassays indicating different mode of action.

Science.gov (United States)

Han, Yingnan; Li, Na; Oda, Yoshimitsu; Ma, Mei; Rao, Kaifeng; Wang, Zijian; Jin, Wei; Hong, Gang; Li, Zhiguo; Luo, Yi

2016-11-01

With the burgeoning contamination of surface waters threatening human health, the genotoxic effects of surface waters have received much attention. Because mutagenic and carcinogenic compounds in water cause tumors by different mechanisms, a battery of bioassays that each indicate a different mode of action (MOA) is required to evaluate the genotoxic effects of contaminants in water samples. In this study, 15 water samples from two source water reservoirs and surrounding rivers in Shijiazhuang city of China were evaluated for genotoxic effects. Target chemical analyses of 14 genotoxic pollutants were performed according to the Environmental quality standards for surface water of China. Then, the in vitro cytokinesis-block micronucleus (CBMN) assay, based on a high-content screening technique, was used to detect the effect of chromosome damage. The SOS/umu test using strain TA1535/pSK1002 was used to detect effects on SOS repair of gene expression. Additionally, two other strains, NM2009 and NM3009, which are highly sensitive to aromatic amines and nitroarenes, respectively, were used in the SOS/umu test to avoid false negative results. In the water samples, only two of the genotoxic chemicals listed in the water standards were detected in a few samples, with concentrations that were below water quality standards. However, positive results for the CBMN assay were observed in two river samples, and positive results for the induction of umuC gene expression in TA1535/pSK1002 were observed in seven river samples. Moreover, positive results were observed for NM2009 with S9 and NM3009 without S9 in some samples that had negative results using the strain TA1535/pSK1002. Based on the results with NM2009 and NM3009, some unknown or undetected aromatic amines and nitroarenes were likely in the source water reservoirs and the surrounding rivers. Furthermore, these compounds were most likely the causative pollutants for the genotoxic effect of these water samples. Therefore

Mixture Genotoxicity of 2,4-Dichlorophenoxyacetic Acid, Acrylamide, and Maleic Hydrazide on Human Caco-2 Cells Assessed with Comet Assay

DEFF Research Database (Denmark)

Syberg, Kristian; Binderup, Mona-Lise; Cedergreen, Nina

2015-01-01

Assessment of genotoxic properties of chemicals is mainly conducted only for single chemicals, without taking mixture genotoxic effects into consideration. The current study assessed mixture effects of the three known genotoxic chemicals, 2,4-dichlorophenoxyacetic acid (2,4-D), acrylamide (AA......), and maleic hydrazide (MH), in an experiment with a fixed ratio design setup. The genotoxic effects were assessed with the single-cell gel electrophoresis assay (comet assay) for both single chemicals and the ternary mixture. The concentration ranges used were 0-1.4, 0-20, and 0-37.7 mM for 2,4-D, AA, and MH......, respectively. Mixture toxicity was tested with a fixed ratio design at a 10:23:77% ratio for 2.4-D:AA:MH. Results indicated that the three chemicals yielded a synergistic mixture effect. It is not clear which mechanisms are responsible for this interaction. A few possible interactions are discussed...

Genotoxic thresholds, DNA repair, and susceptibility in human populations

International Nuclear Information System (INIS)

Jenkins, Gareth J.S.; Zair, Zoulikha; Johnson, George E.; Doak, Shareen H.

2010-01-01

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

Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water

Science.gov (United States)

Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water**

Science.gov (United States)

Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

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.

Integrated analysis of the ecotoxicological and genotoxic effects of the antimicrobial peptide melittin on Daphnia magna and Pseudokirchneriella subcapitata

International Nuclear Information System (INIS)

Galdiero, Emilia; Maselli, Valeria; Falanga, Annarita; Gesuele, Renato; Galdiero, Stefania; Fulgione, Domenico; Guida, Marco

2015-01-01

Melittin is a major constituent of the bee venom of Apis mellifera with a broad spectrum of activities. Melittin therapeutical potential is subject to its toxicity and the assessment of ecotoxicity and genotoxicity is of particular interest for therapeutic use. Here we analyzed the biological effects of melittin on two aquatic species, which are representative of two different levels of the aquatic trophic chain: the invertebrate Daphnia magna and the unicellular microalgae Pseudokirchneriella subcapitata. The attention was focused on the determination of: i) ecotoxicity; ii) genotoxicity; iii) antigenotoxicity. Our main finding is that melittin is detrimental to D. magna reproduction and its sub-lethal concentrations create an accumulation dependent on exposition times and a negative effect on DNA. We also observed that melittin significantly delayed time to first eggs. Moreover, results showed that melittin exerted its toxic and genotoxic effects in both species, being a bit more aggressive towards P. subcapitata. - Highlights: • We examine ecotoxicity to study how AMPs affect the environment. • We examine genotoxicity in order to analyze the damages to the DNA. • We examine the antigenotoxicity in order to verify DNA repair ability of the cells. • Possible therapeutical applications of AMPs depend on assessment of ecotoxicity. - Melittin exerts its dose dependent toxic and genotoxic effects on both indicators; no toxicity is found at concentrations that may typically reach the environment

Fine-scale assessment of home ranges and activity patterns for resident black vultures (Coragyps atratus and turkey vultures (Cathartes aura.

Directory of Open Access Journals (Sweden)

Amanda E Holland

Full Text Available Knowledge of black vulture (Coragyps atratus and turkey vulture (Cathartes aura spatial ecology is surprisingly limited despite their vital ecological roles. Fine-scale assessments of space use patterns and resource selection are particularly lacking, although development of tracking technologies has allowed data collection at finer temporal and spatial resolution. Objectives of this study were to conduct the first assessment of monthly home range and core area sizes of resident black and turkey vultures with consideration to sex, as well as elucidate differences in monthly, seasonal, and annual activity patterns based on fine-scale movement data analyses. We collected 2.8-million locations for 9 black and 9 turkey vultures from June 2013 -August 2015 using solar-powered GSM/GPS transmitters. We quantified home ranges and core areas using the dynamic Brownian bridge movement model and evaluated differences as a function of species, sex, and month. Mean monthly home ranges for turkey vultures were ~50% larger than those of black vultures, although mean core area sizes did not differ between species. Turkey vulture home ranges varied little across months, with exception to a notable reduction in space-use in May, which corresponds with timing of chick-rearing activities. Black vulture home ranges and core areas as well as turkey vulture core areas were larger in breeding season months (January-April. Comparison of space use between male and female vultures was only possible for black vultures, and space use was only slightly larger for females during breeding months (February-May. Analysis of activity patterns revealed turkey vultures spend more time in flight and switch motion states (between flight and stationary more frequently than black vultures across temporal scales. This study reveals substantive variability in space use and activity rates between sympatric black and turkey vultures, providing insights into potential behavioral mechanisms

Potential genotoxic and cytotoxicity of emamectin benzoate in human normal liver cells.

Science.gov (United States)

Zhang, Zhijie; Zhao, Xinyu; Qin, Xiaosong

2017-10-10

Pesticide residue inducing cancer-related health problems draw people more attention recently. Emamectin benzoate (EMB) has been widely used in agriculture around the world based on its specificity targets. Although potential risk and the molecular mechanism of EMB toxicity to human liver has not been well-characterized. Unlike well-reported toxicity upon central nervous system, potential genotoxic and cytotoxicity of EMB in human liver cell was ignored and very limited. In this study, we identify genotoxicity and cytotoxicity of EMB to human normal liver cells (QSG7701 cell line) in vitro . We demonstrate that EMB inhibited the viability of QSG7701 cells and induced the DNA damage. Established assays of cytotoxicity were performed to characterize the mechanism of EMB toxicity on QSG7701 cells. Typical chromatin condensation and DNA fragmentation indicated the apoptosis of QSG7701 cells induced by EMB. And the intracellular biochemical results demonstrated that EMB-enhanced apoptosis of QSG7701 cells concurrent with generated ROS, a loss of mitochondrial membrane potential, the cytochrome-c release, up regulate the Bax/Bcl-2 and the activation of caspase-9/-3. Our results of EMB induces the death of QSG7701 cells maybe via mitochondrial-mediated intrinsic apoptotic pathways would contribute to promote the awareness of EMB as an extensive used pesticide to human being effects and reveal the underlying mechanisms of potential genotoxic.

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

OpenAIRE

Ming W. Chou; Ge Lin; Qingsu Xia; Peter P. Fu

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 ...

Assessment of Genotoxic Potential of Hridayarnava Rasa (A Herbo-Mineralo-Metallic Ayurvedic Formulation) Using Chromosomal Aberration and Sperm Abnormality Assays

Science.gov (United States)

Jagtap, Chandrashekhar Y.; Chaudhari, Swapnil Y.; Thakkar, Jalaram H.; Galib, R.; Prajapati, P. K.

2014-01-01

Objectives: Herbo-mineral formulations are being successfully used in therapeutics since centuries. But recently, they came under the scanner for their metallic contents especially the presence of heavy metals. Hence it is the need of the hour to assess and establish the safety of these formulations through toxicity studies. In line with the various toxicity studies that are being carried out, Government of India expressed the need for conducting genotoxicity studies of different metal- or mineral-based drugs. Till date very few Ayurvedic herbo-mineral formulations have been studied for their genotoxic potential. The present study is aimed to evaluate the genotoxic potential of Hridayarnava Rasa. 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 done to evaluate the genotoxic potential of the test drugs. Cyclophosphamide (CP) was taken as positive group and results were compared. Results: All treated groups exhibited significant body weight gain in comparison to CP group. Results revealed no structural deformity in the above parameters in comparison to the CP-treated group. Conclusion: Reported data showed that both tested samples of Hridayarnava Rasa does not possess genotoxic potential under the experimental conditions and can be safely used. PMID:25948961

A re-assessment of the safety of silver in household water treatment: rapid systematic review of mammalian in vivo genotoxicity studies.

Science.gov (United States)

Fewtrell, Lorna; Majuru, Batsirai; Hunter, Paul R

2017-06-20

Despite poor evidence of their effectiveness, colloidal silver and silver nanoparticles are increasingly being promoted for treating potentially contaminated drinking water in low income countries. Recently, however, concerns have been raised about the possible genotoxicity of particulate silver. The goal of this paper was to review the published mammalian in vivo genotoxicity studies using silver micro and nanoparticles. SCOPUS and Medline were searched using the following search string: ("DNA damage" OR genotox* OR Cytotox* OR Embryotox*) AND (silver OR AgNP). Included papers were any mammalian in vivo experimental studies investigating genotoxicity of silver particles. Studies were quality assessed using the ToxRTool. 16 relevant papers were identified. There were substantial variations in study design including the size of silver particles, animal species, target organs, silver dose, route of administration and the method used to detect genotoxicity. Thus, it was not possible to produce a definitive pooled result. Nevertheless, most studies showed evidence of genotoxicity unless using very low doses. We also identified one human study reporting evidence of "severe DNA damage" in silver jewellery workers occupationally exposed to silver particles. With the available evidence it is not possible to be definitive about risks to human health from oral exposure to silver particulates. However, the balance of evidence suggests that there should be concerns especially when considering the evidence from jewellery workers. There is an urgent need to determine whether people exposed to particulate silver as part of drinking water treatment have evidence of DNA damage.

DNA-synthesis inhibition and repair DNA-synthesis in CHO Ade- C cells: An alternative approach to genotoxicity testing

International Nuclear Information System (INIS)

Slamenova, D.; Papsova, E.; Gabelova, A.; Dusinska, M.; Collins, A.; Wsolova, L.

1997-01-01

We describe an alternative assay to determine genotoxicity. Its main feature is that it combines two measures in a single experiment; the inhibition of replicative DNA synthesis together with the stimulation of DNA repair. We show that, in tests of four different genotoxic agents, the assay gives results that are entirely consistent with what is known about the mode of action of these agents. In addition, we have demonstrated that chemical carcinogens requiring metabolic activation can be examined using a standard procedure of incubation with a microsomal activating fraction. We consider the combined assay for DNA synthesis inhibition and repair synthesis to be a useful way for the rapid pre-screening of chemicals suspected of genotoxic activity on the level of mammalian cells. (author)

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. Copyright © 2013 Elsevier Ltd. All rights reserved.

Physicochemical characteristics, mutagenicity and genotoxicity of airborne particles under industrial and rural influences in Northern Lebanon.

Science.gov (United States)

Melki, Pamela N; Ledoux, Frédéric; Aouad, Samer; Billet, Sylvain; El Khoury, Bilal; Landkocz, Yann; Abdel-Massih, Roula M; Courcot, Dominique

2017-08-01

In this work, the main objectives were to assess the mutagenic and genotoxic effects of fine particulate matter collected in an industrial influenced site in comparison with a non-industrial influenced one (rural site) and to relate the particulate matter (PM) composition to the observed genotoxic effects. At the industrial influenced site, higher concentrations of phosphates, trace metals, and polycyclic aromatic hydrocarbons (PAHs) in particles could be related to the contributions of quarries, fertilizer producer, cement plants, and tires burning. Gasoline and diesel combustion contributions were evidenced in particles collected at both sites. Particles collected under industrial influence showed a higher mutagenic potential on three tested strains of Salmonella typhimurium (TA98, YG1041, and TA102), and especially on the YG1041, compared to particles from the rural site. Furthermore, only particles collected in the vicinity of the industrial site showed a tendency to activate the SOS responses in Escherichia coli PQ37, which is indicative of DNA damage as a result of exposure of the bacteria cells to the action of mutagenic samples. The mutagenicity and genotoxicity of the industrial PM 2.5-0.3 particulates may be attributed to its composition especially in organic compounds. This study showed that proximity of industries can affect local PM composition as well as PM genotoxic and mutagenic potential.

CT in colon cancer

International Nuclear Information System (INIS)

Fujita, Nobuyuki; Hasegawa, Takashi; Kubo, Kozo; Ogawa, Hajime; Sato, Yukihiko; Tomita, Masayoshi; Hanawa, Makoto; Matsuzawa, Tohru; Nishioka, Ken

1990-01-01

CT pictures from 59 lesions of advanced colon cancer including rectal cancer were reviewed to evaluate a role of CT in preoperative staging diagnosis. CT findings were recorded following general rules for clinical and pathological studies on cancer of colon rectum and anus, proposed by Japanese society for cancer of colon and rectum. Tumors were detected in 90% of advanced colon cancers. Sensitivity in local extension (S factor) was 58.0%. Sensitivity in lymphonode involvement (N factor) was 50.0%. Sensitivity in final staging diagnosis, dividing colon cancer into two groups below st II and above st III, was 63.3%. Further study should be necessitated to provide useful information for preoperative staging diagnosis of colon cancer. (author)

Contributions of DNA repair and damage response pathways to the non-linear genotoxic responses of alkylating agents

Science.gov (United States)

Klapacz, Joanna; Pottenger, Lynn H.; Engelward, Bevin P.; Heinen, Christopher D.; Johnson, George E.; Clewell, Rebecca A.; Carmichael, Paul L.; Adeleye, Yeyejide; Andersen, Melvin E.

2016-01-01

From a risk assessment perspective, DNA-reactive agents are conventionally assumed to have genotoxic risks at all exposure levels, thus applying a linear extrapolation for low-dose responses. New approaches discussed here, including more diverse and sensitive methods for assessing DNA damage and DNA repair, strongly support the existence of measurable regions where genotoxic responses with increasing doses are insignificant relative to control. Model monofunctional alkylating agents have in vitro and in vivo datasets amenable to determination of points of departure (PoDs) for genotoxic effects. A session at the 2013 Society of Toxicology meeting provided an opportunity to survey the progress in understanding the biological basis of empirically-observed PoDs for DNA alkylating agents. Together with the literature published since, this review discusses cellular pathways activated by endogenous and exogenous alkylation DNA damage. Cells have evolved conserved processes that monitor and counteract a spontaneous steady-state level of DNA damage. The ubiquitous network of DNA repair pathways serves as the first line of defense for clearing of the DNA damage and preventing mutation. Other biological pathways discussed here that are activated by genotoxic stress include post-translational activation of cell cycle networks and transcriptional networks for apoptosis/cell death. The interactions of various DNA repair and DNA damage response pathways provide biological bases for the observed PoD behaviors seen with genotoxic compounds. Thus, after formation of DNA adducts, the activation of cellular pathways can lead to the avoidance a mutagenic outcome. The understanding of the cellular mechanisms acting within the low-dose region will serve to better characterize risks from exposures to DNA-reactive agents at environmentally-relevant concentrations. PMID:27036068

Fipronil-induced genotoxicity and DNA damage in vivo: Protective effect of vitamin E.

Science.gov (United States)

Badgujar, P C; Selkar, N A; Chandratre, G A; Pawar, N N; Dighe, V D; Bhagat, S T; Telang, A G; Vanage, G R

2017-05-01

Fipronil, an insecticide of the phenylpyrazole class has been classified as a carcinogen by United States Environmental Protection Agency, yet very limited information is available about its genotoxic effects. Adult male and female animals were gavaged with various doses of fipronil (2.5, 12.5, and 25 mg/kg body weight (bw)) to evaluate micronucleus test (mice), chromosome aberration (CA), and comet assay (rats), respectively. Cyclophosphamide (40 mg/kg bw; intraperitoneal) was used as positive control. Another group of animals were pretreated with vitamin E orally (400 mg/kg bw) for 5 days prior to administration of fipronil (12.5 mg/kg). Fipronil exposure in both male and female mice caused significant increase in the frequency of micronuclei (MN) in polychromatic erythrocytes. Similarly, structural CAs in bone marrow cells and DNA damage in the lymphocytes was found to be significantly higher in the male and female rats exposed to fipronil as compared to their respective controls. The average degree of protection (male and female animals combined together) shown by pretreatment of vitamin E against fipronil-induced genotoxicity was 63.28%: CAs; 47.91%: MN formation; and 74.70%: DNA damage. Findings of this study demonstrate genotoxic nature of fipronil regardless of gender effect and documents protective role of vitamin E.

In Vitro Evaluation of Genotoxic Effects under Magnetic Resonant Coupling Wireless Power Transfer

Directory of Open Access Journals (Sweden)

Kohei Mizuno

2015-04-01

Full Text Available 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.

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. Copyright © 2013 Elsevier Ltd. All rights reserved.

Measurement of DNA integrity in marine gastropods as biomarker of genotoxicity

Digital Repository Service at National Institute of Oceanography (India)

Sarkar, A.; Vashistha, D.; Gupta, N.; Malik, K.; Gaitonde, D.C.S.

to identify the hot spot of pollution due to genotoxic compounds, the DNA damage was measured in terms of the loss of DNA integrity in marine gastropods due to the occurrence of DNA strand breaks following the technique of time dependent partially alkaline...

Intermediate frequency magnetic field generated by a wireless power transmission device does not cause genotoxicity in vitro.

Science.gov (United States)

Shi, Dejing; Zhu, Chunbo; Lu, Rengui; Mao, Shitong; Qi, Yanhua

2014-10-01

The aim of this study was to evaluate effects of intermediate frequency magnetic fields (IFMF) generated by a wireless power transmission (WPT) based on magnetic resonance from the perspective of cellular genotoxicity on cultured human lens epithelial cells (HLECs). We evaluated the effects of exposure to 90 kHz magnetic fields at 93.36 µT on cellular genotoxicity in vitro for 2 and 4 h. The magnetic flux density is approximately 3.5 times higher than the reference level recommended by the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines. For assessment of genotoxicity, we studied cellular proliferation, apoptosis and DNA damage by Cell Counting Kit-8 (CCK-8) assay, flow cytometry analysis, alkaline comet assay and phosphorylated histone H2AX (γH2AX) foci formation test. We did not detect any effect of a 90 kHz IFMF generated by WPT based on magnetic resonance on cell proliferation, apoptosis, comet assay, and γH2AX foci formation test. Our results indicated that exposure to 90 kHz IFMF generated by WPT based on magnetic resonance at 93.36 µT for 2 and 4 h does not cause detectable cellular genotoxicity. © 2014 Wiley Periodicals, Inc.

Utilization of Photochemically Induced Fluorescence Detection for HPLC Determination of Genotoxic Impurities in the Vortioxetine Manufacturing Process.

Science.gov (United States)

Douša, Michal; Doubský, Jan; Srbek, Jan

2016-07-01

An analytical reversed-phase high-performance liquid chromatography (HPLC) method for the detection and quantitative determination of two genotoxic impurities at ppm level present in the vortioxetine manufacturing process is described. Applying the concept of threshold of toxicological concern, a limit of 75 ppm each for both genotoxic impurities was calculated based on the maximum daily dose of active pharmaceutical ingredients. The novel reversed-phase HPLC method with photochemically induced fluorescence detection was developed on XSELECT Charged Surface Hybrid Phenyl-Hexyl column using the mobile phase consisted a mixture of 10 mM ammonium formate pH 3.0 and acetonitrile. The elution was performed using an isocratic composition of 48:52 (v/v) at a flow rate of 1.0 mL/min. The photochemically induced fluorescence detection is based on the use of UV irradiation at 254 nm through measuring the fluorescence intensity at 300 nm and an excitation wavelength of 272 nm to produce fluorescent derivatives of both genotoxic impurities. The online photochemical conversion and detection is easily accomplished for two expected genotoxic impurities and provides a sufficiently low limit detection and quantification for the target analysis. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

QSAR pre-screen of 70,983 substances for genotoxic carcinogenicity, mutagenicity and developmental toxicity in the EU FP7 project ChemScreen

DEFF Research Database (Denmark)

Wedebye, Eva Bay; Dybdahl, Marianne; Nikolov, Nikolai Georgiev

2014-01-01

be performed in REACH on known genotoxic carcinogens or germ cell mutagens with appropriate risk management measures implemented, a QSAR pre-screen for genotoxic carcinogenicity, germ cell mutagenicity and (limited) developmental toxicity was included in the project. Predictions for estrogenic and anti...... algorithms were applied to combine the predictions from the individual models to reach overall predictions for genotoxic carcinogenicity, germ cell mutagenicity and developmental toxicity. Furthermore, the full list of REACH pre-registered substances (143,835) was searched for substances containing certain...

Genotoxicity of water from the Songhua River, China, in 1994-1995 and 2002-2003: Potential risks for human health

International Nuclear Information System (INIS)

Liu Jiaren; Dong Hongwei; Tang Xuanle; Sun Xiangrong; Han Xiaohui; Chen Bingqing; Sun Changhao; Yang Baofeng

2009-01-01

A previous study showed that the cancer mortalities are higher for residents who lived nearby the Songhua River heavily polluted by organic contamination. It is important to determine its risk of carcinogenic potential. Short-term genotoxic bio-assays using Salmonella, Sister Chromatid Exchange (SCE), and Micronuclei (MN) assays were employed to examine the genotoxic activity of ether extracts of water samples taken from the Songhua River. The results of the Salmonella bioassay indicated that there were indirect frame-shift mutagens in the water samples. A dose-response relationship for the SCE and MN assays was obtained. These results showed that organic extracts of water samples have genotoxic activity and the risk of carcinogenic potential to human health. The mutagenesis of water samples had changed compared to the results in 1994-1995. An increasing trend of risk of carcinogenic potential in the Songhua River after ten years should be noted and needs to be studied further. - Organic extracts of water samples taken from the Songhua River have genotoxic activity and the risk of carcinogenic potential to human health

The Vitotox and ToxTracker assays: A two-test combination for quick and reliable assessment of genotoxic hazards.

Science.gov (United States)

Ates, Gamze; Favyts, Dorien; Hendriks, Giel; Derr, Remco; Mertens, Birgit; Verschaeve, Luc; Rogiers, Vera; Y Doktorova, Tatyana

2016-11-01

To ensure safety for humans, it is essential to characterize the genotoxic potential of new chemical entities, such as pharmaceutical and cosmetic substances. In a first tier, a battery of in vitro tests is recommended by international regulatory agencies. However, these tests suffer from inadequate specificity: compounds may be wrongly categorized as genotoxic, resulting in unnecessary, time-consuming, and expensive in vivo follow-up testing. In the last decade, novel assays (notably, reporter-based assays) have been developed in an attempt to overcome these drawbacks. Here, we have investigated the performance of two in vitro reporter-based assays, Vitotox and ToxTracker. A set of reference compounds was selected to span a variety of mechanisms of genotoxic action and applicability domains (e.g., pharmaceutical and cosmetic ingredients). Combining the performance of the two assays, we achieved 93% sensitivity and 79% specificity for prediction of gentoxicity for this set of compounds. Both assays permit quick high-throughput analysis of drug candidates, while requiring only small quantities of the test substances. Our study shows that these two assays, when combined, can be a reliable method for assessment of genotoxicity hazard. Copyright © 2016 Elsevier B.V. All rights reserved.

Genotoxicity induced by Taenia solium and its reduction by immunization with calreticulin in a hamster model of taeniosis.

Science.gov (United States)

Salazar, Ana María; Mendlovic, Fela; Cruz-Rivera, Mayra; Chávez-Talavera, Oscar; Sordo, Monserrat; Avila, Guillermina; Flisser, Ana; Ostrosky-Wegman, Patricia

2013-06-01

Genotoxicity induced by neurocysticercosis has been demonstrated in vitro and in vivo in humans. The adult stage of Taenia solium lodges in the small intestine and is the main risk factor to acquire neurocysticercosis, nevertheless its carcinogenic potential has not been evaluated. In this study, we determined the genotoxic effect of T. solium infection in the hamster model of taeniosis. In addition, we assessed the effect of oral immunization with recombinant T. solium calreticulin (rTsCRT) plus cholera toxin as adjuvant on micronuclei induction, as this protein has been shown to induce 33-44% protection in the hamster model of taeniosis. Blood samples were collected from the orbital venous plexus of noninfected and infected hamsters at different days postinfection, as well as from orally immunized animals, to evaluate the frequency of micronucleated reticulocytes as a measure of genotoxicity induced by parasite exposure and rTsCRT vaccination. Our results indicate that infection with T. solium caused time-dependent DNA damage in vivo and that rTsCRT immunization reduced the genotoxic damage induced by the presence of the tapeworms. Copyright © 2013 Wiley Periodicals, Inc.

Air quality biomonitoring: assessment of air pollution genotoxicity in the Province of Novara (North Italy) by using Trifolium repens L. and molecular markers.

Science.gov (United States)

Piraino, F; Aina, R; Palin, L; Prato, N; Sgorbati, S; Santagostino, A; Citterio, S

2006-12-15

Mixed air pollutants are considered a major cause of DNA damage in living species. In this study Trifolium repens L. cv Regal was used as a bioindicator to assess the genotoxicity of air stressors in the Italian province of Novara. Two on-site biomonitoring experiments were performed during the spring and autumn of 2004. Test plants were exposed at 19 monitoring sites distributed homogeneously throughout the province, and each experiment lasted for a period of 6 weeks. Genotoxicity was evaluated with Amplified Fragment Length Polymorphism (AFLP) molecular markers. The results show the predominantly rural central-west region of the Novara Province to have the worst air quality with regard to genotoxicity. Analyses of geomorphology, land use and climatic factors suggest that the compromised air quality in the region could be attributed to wind strength and direction, transporting pollution from vehicular traffic on the A4 highway and from the urban/industrialized centres of Novara and Vercelli. Plant growth, changes in plant photochemical efficiency and the presence of ozone related leaf injuries were also measured to better interpret the results of genotoxicity. Statistical analyses show that although climatic factors such as light intensity and temperature influence plant growth, they do not contribute to atmospheric stressor-induced DNA damage. Further analyses indicated that, as expected, a mixture of genotoxic and non-genotoxic pollutants coexist in the Novara Province troposphere, and that the elevated ozone concentrations experienced during the study may have contributed to the DNA damage in the tested plants by enhancing genotoxicity via interaction with other air stressors.

Workshop. Assessment of Occupational and Environmental Exposure to Genotoxic Substances - a Methodological Approach

International Nuclear Information System (INIS)

2000-01-01

During the workshop various works concerning radiobiology, environmental and occupational medicine were presented. Exposure to genotoxic and carcinogenic agents, like ionizing radiation, aromatic hydrocarbons, herbicides, pesticides was investigated

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

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 Allium. Pretreatment of Allium sativum with quercetin significantly (P Allium sativum that resides, at least in part, on its antioxidant effects.

Cytotoxic and genotoxic effects caused by 153 Sm-EDTMP, combined with BrdU a thymidine analog

International Nuclear Information System (INIS)

Morales A, E.; Ferro F, G.; Morales R, P.

2006-01-01

The ablation of the bone marrow previous to the transplant by means of radiation and chemical antineoplastics its affect indiscriminately to the healthy tissues and in particular those that are in proliferation. The objective of this work is to determine the effect of the incorporation from the BrdU to the DNA on the genotoxicity and cytotoxicity of the cells of the bone marrow caused by the radiopharmaceutical 153 Sm-EDTMP. The genotoxicity was determined by the rate of erythrocytes polychromatic micro nucleates (EPC-MN) and the cytotoxicity by the frequency of EPC. Both parameters determined in peripheral blood after the BrdU administration and 153 Sm-EDTMP. The combination of the BrdU and r1 radiopharmaceutical produced a bigger cytotoxicity that the radiation and the BrdU alone; on the other hand it produced a reduction of the EPC-MN produced by the radiation, suggesting that the cytotoxicity didn't allow the expression of the genotoxicity. (Author)

Randomly amplified polymorphic-DNA analysis for detecting genotoxic effects of Boron on maize (Zea mays L.).

Science.gov (United States)

Sakcali, M Serdal; Kekec, Guzin; Uzonur, Irem; Alpsoy, Lokman; Tombuloglu, Huseyin

2015-08-01

This study was carried out to investigate the genotoxic effect of boron (B) on maize using randomly amplified polymorphic DNA (RAPD) method. Experimental design was conducted under 0, 5, 10, 25, 50, 100, 125, and 150 ppm B exposures, and physiological changes have revealed a sharp decrease in root growth rates from 28% to 85%, starting from 25 ppm to 150 ppm, respectively. RAPD-polymerase chain reaction (PCR) analysis shows that DNA alterations are clearly observed from beginning to 100 ppm. B-induced inhibition in root growth had a positive correlation with DNA alterations. Total soluble protein, root and stem lengths, and B content analysis in root and leaves encourage these results as a consequence. These preliminary findings reveal that B causes chromosomal aberration and genotoxic effects on maize. Meanwhile, usage of RAPD-PCR technique is a suitable biomarker to detect genotoxic effect of B on maize and other crops for the future. © The Author(s) 2013.

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

Directory of Open Access Journals (Sweden)

María Elena Calderón-Segura

2012-01-01

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

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.

Colonic diverticulosis is not a risk factor for colonic adenoma.

Science.gov (United States)

Hong, Wandong; Dong, Lemei; Zippi, Maddalena; Stock, Simon; Geng, Wujun; Xu, Chunfang; Zhou, Mengtao

2018-01-01

Colonic diverticulosis may represent a risk factor for colonic adenomas by virtue of the fact that evolving data suggest that these 2 conditions may share common risk factors such as Western dietary pattern and physical inactivity. This study aims to investigate the association between colonic diverticulosis and colonic adenomas in mainland China. We conducted a cross-sectional study on patients who underwent colonoscopic examination between October 2013 and December 2014 in a university hospital in mainland China. Age, gender, colonic adenomas, advanced adenomas, and distribution of diverticulosis were recorded during the procedures. Multivariate logistic regression and stratified analysis were used to evaluate the associations between the prevalence of diverticulosis and age, sex, and presence of colonic adenomas and advanced adenomas. A total of 17,456 subjects were enrolled. The prevalence of colonic diverticulosis and adenoma was 2.4% and 13.2%, respectively. With regard to distribution of diverticula, most (365/424, 86.1%) were right-sided. Multiple logistic regression analysis suggested that age and male gender were independent risk factors for adenoma and advanced adenoma. There was no relationship between diverticulosis or location of diverticulosis and presence of adenoma and advanced adenoma adjusting by age and gender. In a stratified analysis according to age and gender, similar results were also noted. There was no statistical relationship between diverticulosis and the risk of adenoma and advanced adenoma. Our results may not be generalized to the Western population due to the fact that left-sided diverticular cases were very small in our study.

Colonic angiodysplasia

International Nuclear Information System (INIS)

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

1984-01-01

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. (orig.)

Human biological monitoring of occupational genotoxic exposures

DEFF Research Database (Denmark)

Knudsen, Lisbeth E.; Sorsa, M

1993-01-01

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......) 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...

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...

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

International Nuclear Information System (INIS)

Esperanza, Marta; Cid, Ángeles; Herrero, Concepción; Rioboo, Carmen

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-08-15

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

Amplification of arsenic genotoxicity by TiO2 nanoparticles in mammalian cells: new insights from physicochemical interactions and mitochondria.

Science.gov (United States)

Wang, Xinan; Liu, Yun; Wang, Juan; Nie, Yaguang; Chen, Shaopeng; Hei, Tom K; Deng, Zhaoxiang; Wu, Lijun; Zhao, Guoping; Xu, An

2017-10-01

Titanium dioxide nanoparticles (TiO 2 NPs) have shown great adsorption capacity for arsenic (As); however, the potential impact of TiO 2 NPs on the behavior and toxic responses of As remains largely unexplored. In the present study, we focused on the physicochemical interaction between TiO 2 NPs and As(III) to clarify the underlying mechanisms involved in their synergistic genotoxic effect on mammalian cells. Our data showed that As(III) mainly interacted with TiO 2 NPs by competitively occupying the sites of hydroxyl groups on the surface of TiO 2 NP aggregates, resulting in more aggregation of TiO 2 NPs. Although TiO 2 NPs at concentrations used here had no cytotoxic or genotoxic effects on cells, they efficiently increased the genotoxicity of As(III) in human-hamster hybrid (A L ) cells. The synergistic genotoxicity of TiO 2 NPs and As(III) was partially inhibited by various endocytosis pathway inhibitors while it was completely blocked by an As(III)-specific chelator. Using a mitochondrial membrane potential fluorescence probe, a reactive oxygen species (ROS) probe together with mitochondrial DNA-depleted ρ 0 A L cells, we discovered that mitochondria were essential for mediating the synergistic DNA-damaging effects of TiO 2 NPs and As(III). These data provide novel mechanistic proof that TiO 2 NPs enhanced the genotoxicity of As(III) via physicochemical interactions, which were mediated by mitochondria-dependent ROS.

The cda GenoTox assay: A new and sensitive method for detection of environmental genotoxins, including nitroarenes and aromatic amines

DEFF Research Database (Denmark)

Østergaard, Trine G.; Hansen, Lars Henrik; Binderup, Mona-Lise

2007-01-01

A new bacterial test system for detection of genotoxic compounds was developed, based on two new Sahnonella typhimurium tester strains, TGO1 and TGO2. Both strains contain a gene fusion between a strong SOS-promotor, P-cda, and the gfp gene, which allows detection of genotoxic compounds that indu...

The use of dose-response data in a margin of exposure approach to carcinogenic risk assessment for genotoxic chemicals in food.

Science.gov (United States)

Benford, Diane J

2016-05-01

Genotoxic substances are generally not permitted for deliberate use in food production. However, an appreciable number of known or suspected genotoxic substances occur unavoidably in food, e.g. from natural occurrence, environmental contamination and generation during cooking and processing. Over the past decade a margin of exposure (MOE) approach has increasingly been used in assessing the exposure to substances in food that are genotoxic and carcinogenic. The MOE is defined as a reference point on the dose-response curve (e.g. a benchmark dose lower confidences limit derived from a rodent carcinogenicity study) divided by the estimated human intake. A small MOE indicates a higher concern than a very large MOE. Whilst the MOE cannot be directly equated to risk, it supports prioritisation of substances for further research or for possible regulatory action, and provides a basis for communicating to the public. So far, the MOE approach has been confined to substances for which carcinogenicity data are available. In the absence of carcinogenicity data, evidence of genotoxicity is used only in hazard identification. The challenge to the genetic toxicology community is to develop approaches for characterising risk to human health based on data from genotoxicity studies. In order to achieve wide acceptance, it would be important to further address the issues that have been discussed in the context of dose-response modelling of carcinogenicity data in order to assign levels of concern to particular MOE values, and also whether it is possible to make generic conclusions on how potency in genotoxicity assays relates to carcinogenic potency. © Crown copyright 2015.

A prognostic analysis of 895 cases of stage III colon cancer in different colon subsites.

Science.gov (United States)

Zhang, Yan; Ma, Junli; Zhang, Sai; Deng, Ganlu; Wu, Xiaoling; He, Jingxuan; Pei, Haiping; Shen, Hong; Zeng, Shan

2015-09-01

Stage III colon cancer is currently treated as an entity with a unified therapeutic principle. The aim of the retrospective study is to explore the clinicopathological characteristics and outcomes of site-specific stage III colon cancers and the influences of tumor location on prognosis. Eight hundred ninety-five patients with stage III colon cancer treated with radical operation and subsequent adjuvant chemotherapy (5-fluorouracil/oxaliplatin) were divided into seven groups according to colon segment (cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, and sigmoid colon). Expression of excision repair cross-complementing group 1 (ERCC1) and thymidylate synthase (TS) was examined by immunohistochemistry. We assessed if differences exist in patient characteristics and clinic outcomes between the seven groups. There were significant differences in tumor differentiation (P Cancer (AJCC) tumor-node-metastasis (TNM) stage (P colon. Cox regression analyses identified that tumor location was an independent prognostic factor for RFS and OS. Stage III colon cancer located proximally carried a poorer survival than that located distally. Different efficacies of FOLFOX adjuvant chemotherapy may be an important factor affecting survival of site-specific stage III colon cancers.

QSAR ligand dataset for modelling mutagenicity, genotoxicity, and rodent carcinogenicity

Directory of Open Access Journals (Sweden)

Davy Guan

2018-04-01

Full Text Available Five datasets were constructed from ligand and bioassay result data from the literature. These datasets include bioassay results from the Ames mutagenicity assay, Greenscreen GADD-45a-GFP assay, Syrian Hamster Embryo (SHE assay, and 2 year rat carcinogenicity assay results. These datasets provide information about chemical mutagenicity, genotoxicity and carcinogenicity.

Genotoxicity evaluation of the insecticide ethion in root of Allium ...

African Journals Online (AJOL)

In this study, the genotoxic effects of ethion were investigated in the mitotic cell division of Allium cepa. Primary roots of A. cepa were treated with various concentrations (25, 50, 75, and 100%) of ethion solutions for different duration of time. The result revealed that increase in the concentration and duration of treatment ...

Colonic lipoma

International Nuclear Information System (INIS)

Siddiqui, M.S.; Khatri, A.R.; Quraishy, M.S.; Fatima, L.; Muzaffar, S.

2003-01-01

Lipoma of the colon is rare and may lead to intestinal obstruct. We have presented two cases of colonic lipoma. Both were elderly females, one presented with diarrhea and the other with sub-acute intestinal obstruction. After colonoscopy surgical removal was done. Histopathology revealed lipoma. (author)

A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: genotoxicity. A COLIPA analysis.

Science.gov (United States)

Pfuhler, Stefan; Kirst, Annette; Aardema, Marilyn; Banduhn, Norbert; Goebel, Carsten; Araki, Daisuke; Costabel-Farkas, Margit; Dufour, Eric; Fautz, Rolf; Harvey, James; Hewitt, Nicola J; Hibatallah, Jalila; Carmichael, Paul; Macfarlane, Martin; Reisinger, Kerstin; Rowland, Joanna; Schellauf, Florian; Schepky, Andreas; Scheel, Julia

2010-01-01

For the assessment of genotoxic effects of cosmetic ingredients, a number of well-established and regulatory accepted in vitro assays are in place. A caveat to the use of these assays is their relatively low specificity and high rate of false or misleading positive results. Due to the 7th amendment to the EU Cosmetics Directive ban on in vivo genotoxicity testing for cosmetics that was enacted March 2009, it is no longer possible to conduct follow-up in vivo genotoxicity tests for cosmetic ingredients positive in in vitro genotoxicity tests to further assess the relevance of the in vitro findings. COLIPA, the European Cosmetics Association, has initiated a research programme to improve existing and develop new in vitro methods. A COLIPA workshop was held in Brussels in April 2008 to analyse the best possible use of available methods and approaches to enable a sound assessment of the genotoxic hazard of cosmetic ingredients. Common approaches of cosmetic companies are described, with recommendations for evaluating in vitro genotoxins using non-animal approaches. A weight of evidence approach was employed to set up a decision-tree for the integration of alternative methods into tiered testing strategies. Copyright 2010 Elsevier Inc. All rights reserved.

Genotoxic effects of vinclozolin on the aquatic insect Chironomus riparius (Diptera, Chironomidae).

Science.gov (United States)

Aquilino, Mónica; Sánchez-Argüello, Paloma; Martínez-Guitarte, José-Luis

2018-01-01

Vinclozolin (Vz) is a pollutant found in aquatic environments whose antiandrogenic effects in reproduction are well known in mammals. Although its reproductive effects have been less studied in invertebrates, other effects, including genotoxicity, have been described. Therefore, in this work, we studied the genotoxic effects of Vz in the freshwater benthic invertebrate Chironomus riparius. DNA damage was evaluated with the comet assay (tail area, olive moment, tail moment and % DNA in tail), and the transcriptional levels of different genes involved in DNA repair (ATM, NLK and XRCC1) and apoptosis (DECAY) were measured by RT-PCR. Fourth instar larvae of C. riparius, were exposed to Vz for 24 h at 20 and 200 μg/L. The Vz exposures affected the DNA integrity in this organism, since a dose-response relationship occurred, with DNA strand breaks significantly increased with increased dose for tail area, olive moment and tail moment parameters. Additionally, the lower concentration of Vz produced a significant induction of the transcripts of three genes under study (ATM, NLK and XRCC1) showing the activation of the cellular repair mechanism. In contrast, the expression of these genes with the highest concentration were downregulated, indicating failure of the cellular repair mechanism, which would explain the higher DNA damage. These data report for the first time the alterations of Vz on gene transcription of an insect and confirm the potential genotoxicity of this compound on freshwater invertebrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Contributions of DNA repair and damage response pathways to the non-linear genotoxic responses of alkylating agents.

Science.gov (United States)

Klapacz, Joanna; Pottenger, Lynn H; Engelward, Bevin P; Heinen, Christopher D; Johnson, George E; Clewell, Rebecca A; Carmichael, Paul L; Adeleye, Yeyejide; Andersen, Melvin E

2016-01-01

From a risk assessment perspective, DNA-reactive agents are conventionally assumed to have genotoxic risks at all exposure levels, thus applying a linear extrapolation for low-dose responses. New approaches discussed here, including more diverse and sensitive methods for assessing DNA damage and DNA repair, strongly support the existence of measurable regions where genotoxic responses with increasing doses are insignificant relative to control. Model monofunctional alkylating agents have in vitro and in vivo datasets amenable to determination of points of departure (PoDs) for genotoxic effects. A session at the 2013 Society of Toxicology meeting provided an opportunity to survey the progress in understanding the biological basis of empirically-observed PoDs for DNA alkylating agents. Together with the literature published since, this review discusses cellular pathways activated by endogenous and exogenous alkylation DNA damage. Cells have evolved conserved processes that monitor and counteract a spontaneous steady-state level of DNA damage. The ubiquitous network of DNA repair pathways serves as the first line of defense for clearing of the DNA damage and preventing mutation. Other biological pathways discussed here that are activated by genotoxic stress include post-translational activation of cell cycle networks and transcriptional networks for apoptosis/cell death. The interactions of various DNA repair and DNA damage response pathways provide biological bases for the observed PoD behaviors seen with genotoxic compounds. Thus, after formation of DNA adducts, the activation of cellular pathways can lead to the avoidance of a mutagenic outcome. The understanding of the cellular mechanisms acting within the low-dose region will serve to better characterize risks from exposures to DNA-reactive agents at environmentally-relevant concentrations. Copyright © 2015 Elsevier B.V. All rights reserved.

Genotoxicity in earthworm after combined treatment of ionising radiation and mercury

International Nuclear Information System (INIS)

Ryu, Tae Ho; Kim, Jin Kyu; An, Kwang-Guk

2014-01-01

This study was performed to investigate the acute genotoxic effects of mercury and radiation on earthworms (Eisenia fetida). The levels of DNA damage and the repair kinetics in the coelomocytes of E. fetida treated with mercuric chloride (HgCl 2 ) and ionising radiation (gamma rays) were analysed by means of the comet assay. For detection of DNA damage and repair, E. fetida was exposed to HgCl 2 (0-160 mg kg -1 ) and irradiated with gamma rays (0-50 Gy) in vivo. The increase in DNA damage depended on the concentration of mercury or dose of radiation. The results showed that the more the oxidative stress induced by mercury and radiation the longer the repair time that was required. When a combination of HgCl 2 and gamma rays was applied, the cell damage was much higher than those treated with HgCl 2 or radiation alone, which indicated that the genotoxic effects were increased after the combined treatment of mercury and radiation. (authors)

Management of Colonic Volvulus

Science.gov (United States)

Gingold, Daniel; Murrell, Zuri

2012-01-01

Colonic volvulus is a common cause of large bowel obstruction worldwide. It can affect all parts of the colon, but most commonly occurs in the sigmoid and cecal areas. This disease has been described for centuries, and was studied by Hippocrates himself. Currently, colonic volvulus is the third most common cause of large bowel obstruction worldwide, and is responsible for ∼15% of large bowel obstructions in the United States. This article will discuss the history of colonic volvulus, and the predisposing factors that lead to this disease. Moreover, the epidemiology and diagnosis of each type of colonic volvulus, along with the various treatment options will be reviewed. PMID:24294126

CT findings of colonic diverticulitis

International Nuclear Information System (INIS)

Sasaki, Shigeru; Ohba, Satoru; Mizutani, Masaru

1998-01-01

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)

Genotoxic action of sunlight upon Bacillus subtilis spores

International Nuclear Information System (INIS)

Munakata, Nobuo

1989-01-01

Samples of Bacillus subtilis spores dried on membrane filter were exposed to natural sunlight from solar-noon time at Tokyo. The survival and mutation induction of wild-type (UVR) and repair-deficient (UVS) spores were determined on 66 occasions since 1979. Two of the values were considered to be useful in monitoring solar UV intensity; the inverse of the time (in minutes) of exposure to kill 63% of the UVS spores ('sporocidal index') and the induced mutation frequency at 60 minutes of exposure of the UVR spores ('mutagenic index'). Both values were varied greatly due to time of a year, weather and other conditions. Estimates of year-round changes under clear skies were obtained by connecting the maximum values attained in these years. In these curves, there are more than 7-fold differences in the genotoxicity between winter and summer months, with major increases observed in early spring and decreases through autumn. Using a series of UV cut-off filters, the wavelengths most effective for the sporocidal actions were estimated to be in the range of 308 - 325 nm, shorter wavelengths being effective when the genotoxicity was higher. Sunburn meter of Robertson-Berger type seems to respond to slightly longer wavelength components of the solar spectrum. However, a reasonable correlation was obtained between the reading of the meter and the sporocidal index. (author)

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Decisions to regulate genotoxic substances

Energy Technology Data Exchange (ETDEWEB)

Bengtsson, G

1988-07-01

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

Decisions to regulate genotoxic substances

International Nuclear Information System (INIS)

Bengtsson, G.

1988-01-01

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

Genotoxic activities of the food contaminant 5-hydroxymethylfurfural using different in vitro bioassays.

Science.gov (United States)

Severin, Isabelle; Dumont, Coralie; Jondeau-Cabaton, Adeline; Graillot, Vanessa; Chagnon, Marie-Christine

2010-02-01

5-Hydroxymethylfurfural (5-HMF) is known as an indicator of quality deterioration in a wide range of foods. 5-HMF is formed as an intermediate in the Maillard reaction and has been identified in a wide variety of heat-processed foods. In recent years, the presence of 5-HMF in foods has raised toxicological concerns: data have shown cytotoxic, genotoxic and tumoral effects but further studies suggest that 5-HMF does not pose a serious health risk. However the subject is still a matter of debate. We investigated the genotoxicity of the food-borne contaminant 5-HMF using the Ames test, the micronucleus (MN) and the single-cell gel electrophoresis (SCGE) assays in the human metabolically active HepG2 cell line. Cytotoxic effect of 5-HMF was first assessed using Alamar Blue as a sensitive sub-lethal assay. 5-HMF did not induce any genic mutation in bacteria whatever the concentration in the Ames test. Furthermore, it does not induce clastogenic or aneugenic effects in the HepG2 cells. In contrast, 5-HMF induced HepG2 DNA damage at concentrations from 7.87 to 25 mM in the comet assay suggesting a weak genotoxic effect of 5-HMF in the HepG2 cells probably repaired. 2009 Elsevier Ireland Ltd. All rights reserved.

High-throughput in vivo genotoxicity testing: an automated readout system for the somatic mutation and recombination test (SMART.

Directory of Open Access Journals (Sweden)

Benoit Lombardot

Full Text Available Genotoxicity testing is an important component of toxicity assessment. As illustrated by the European registration, evaluation, authorization, and restriction of chemicals (REACH directive, it concerns all the chemicals used in industry. The commonly used in vivo mammalian tests appear to be ill adapted to tackle the large compound sets involved, due to throughput, cost, and ethical issues. The somatic mutation and recombination test (SMART represents a more scalable alternative, since it uses Drosophila, which develops faster and requires less infrastructure. Despite these advantages, the manual scoring of the hairs on Drosophila wings required for the SMART limits its usage. To overcome this limitation, we have developed an automated SMART readout. It consists of automated imaging, followed by an image analysis pipeline that measures individual wing genotoxicity scores. Finally, we have developed a wing score-based dose-dependency approach that can provide genotoxicity profiles. We have validated our method using 6 compounds, obtaining profiles almost identical to those obtained from manual measures, even for low-genotoxicity compounds such as urethane. The automated SMART, with its faster and more reliable readout, fulfills the need for a high-throughput in vivo test. The flexible imaging strategy we describe and the analysis tools we provide should facilitate the optimization and dissemination of our methods.

Evaluation of genotoxic effects caused by extracts of chlorinated drinking water using a combination of three different bioassays.

Science.gov (United States)

Zeng, Qiang; Zhang, Shao-Hui; Liao, Jing; Miao, Dong-Yue; Wang, Xin-Yi; Yang, Pan; Yun, Luo-Jia; Liu, Ai-Lin; Lu, Wen-Qing

2015-10-15

Potential genotoxic effects of chlorinated drinking water now are of a great concern. In this study, raw water, finished water, and tap water from a water plant in Wuhan, China were collected in two different sampling times of the year (January and July). Genotoxic effects of water extracts were evaluated using a combination of three different bioassays: SOS/umu test, HGPRT gene mutation assay, and micronucleus assay, which were separately used to detect DNA damage, gene mutation, and chromosome aberration. The results of three different bioassays showed that all water samples in January and July induced at least one types of genotoxic effects, of which the DNA-damage effects were all detectable. The levels of DNA-damage effects and gene-mutation effects of finished water and tap water in January were higher than those in July. Chlorination could increase the DNA-damage effects of drinking water in January and the gene-mutation effects of drinking water in both January and July, but did not increase the chromosome-aberration effects of drinking water in both January and July. Our results highlighted the importance of using a combination of different bioassays to evaluate the genotoxicity of water samples in different seasons. Copyright © 2015 Elsevier B.V. All rights reserved.

Genotoxic effects and oxidative stress induced by organic extracts of particulate matter(PM 10)collected from a subway tunnel in Seoul, Korea.

Science.gov (United States)

Jung, Mi Hyun; Kim, Ha Ryong; Park, Yong Joo; Park, Duck Shin; Chung, Kyu Hyuck; Oh, Seung Min

2012-12-12

Particulate matter (PM) has become an important health risk factor in our society. PM can easily deposit in the bronchi and lungs, causing diverse diseases such as respiratory infections, lung cancers and cardiovascular diseases. In recent days, more and more toxicological studies have been dealing with air particles in distinctive areas including industrial areas, transportation sites, or indoors. Studies on subway PM in particular, have been recognizing PM as an important health risk factor because many people use subways as a major mode of public transportation (4 million people a day in Korea). The main aim of the present study was to evaluate the genotoxic effects of organic extract (OE) of subway PM10 and potential attribution of PAHs to these effects. Particles were collected in the subway tunnel at Kil-eum station(Line 4) for one month and then extracted with Dichloromethane (DCM). Chinese Hamster Ovary cells(CHO-K1) and human normal bronchial cells (BEAS-2B) were exposed to OE, and MN and Comet assays were conducted to analyze the genotoxicity. The results showed that OE increased DNA or chromosome damages in both cell lines. In the modified Comet assay and MN assay with free radical scavengers, we confirmed that the genotoxic effect of OE was partially due to the oxidative damage on DNA. DCFHD Aassay also indicated that OE induced ROS generation in BEAS-2B cells. PAHs [benzo(a)anthracene,benzo(k)fluoranthrene, etc.], the most well-known carcinogens in polluted air, were detected in Kil-eum PM10. In conclusion, our findings confirmed that OE of subway PM10 has genotoxic effects on normal human lung cells, and oxidative stress could be one of the major mechanisms of these genotoxic effects.In addition, some genotoxic and carcinogenic PAHs were detected in OE by GC/MS/MS, even though PAHs level was not enough to increase CYP1A1 gene. Therefore, we suggest that additive or synergistic effects by unidentified chemicals as well as PAHs contained in OE of subway

Effects of dietary antioxidants and 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) on preneoplastic lesions and on oxidative damage, hormonal status, and detoxification capacity in the rat

DEFF Research Database (Denmark)

Breinholt, Vibeke M.; Mølck, Anne-Marie; Svendsen, Gitte Winkel

2003-01-01

mechanisms were assayed in blood, liver and colon and the impact of the antioxidant administrations on putative preneoplastic changes in liver and colon was assessed. The dietary carcinogen, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) (200 mg/kg diet) served as a pro-oxidant, genotoxicity and general...

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

Genotoxicity assessment of membrane concentrates of landfill leachate treated with Fenton reagent and UV-Fenton reagent using human hepatoma cell line

Energy Technology Data Exchange (ETDEWEB)

Wang, Guifang [Department of Chemistry, Jinan University, Guangzhou 510632 (China); Lu, Gang [Key Laboratory of Water/Soil Toxic Pollutants Control and Bioremediation of Guangdong Higher Education Institutes, Department of Environmental Engineering, Jinan University, Guangzhou 510632 (China); Yin, Pinghe, E-mail: tyinph@jnu.edu.cn [Research Center of Analysis and Test, Jinan University, Guangzhou 510632 (China); Zhao, Ling, E-mail: zhaoling@jnu.edu.cn [Key Laboratory of Water/Soil Toxic Pollutants Control and Bioremediation of Guangdong Higher Education Institutes, Department of Environmental Engineering, Jinan University, Guangzhou 510632 (China); Jimmy Yu, Qiming [Griffith School of Engineering, Griffith University, Nathan Campus, Brisbane, Queensland 4111 (Australia)

2016-04-15

Highlights: • Membrane concentrates have a threat to human health and environment. • Untreated membrane concentrates induces cytotoxic and genotoxic to HepG2 cells. • Both methods were effective method for degradation of BPA and NP in concentrates. • Both methods were efficient in reducing genotoxic effects of concentrates. • UV-Fenton reagent had higher removal efficiency and provides toxicological safety. - Abstract: Membrane concentrates of landfill leachates contain organic and inorganic contaminants that could be highly toxic and carcinogenic. In this paper, the genotoxicity of membrane concentrates before and after Fenton and UV-Fenton reagent was assessed. The cytotoxicity and genotoxicity was determined by using the methods of methyltetrazolium (MTT), cytokinesis-block micronucleus (CBMN) and comet assay in human hepatoma cells. MTT assay showed a cytotoxicity of 75% after 24 h of exposure to the highest tested concentration of untreated concentrates, and no cytotoxocity for UV-Fenton and Fenton treated concentrates. Both CBMN and comet assays showed increased levels of genotoxicity in cells exposed to untreated concentrates, compared to those occurred in cells exposed to UV-Fenton and Fenton reagent treated concentrates. There was no significant difference between negative control and UV-Fenton treated concentrates for micronucleus and comet assay parameters. UV-Fenton and Fenton treatment, especially the former, were effective methods for degradation of bisphenol A and nonylphenol in concentrates. These findings showed UV-Fenton and Fenton reaction were effective methods for treatment of such complex concentrates, UV-Fenton reagent provided toxicological safety of the treated effluent, and the genotoxicity assays were found to be feasible tools for assessment of toxicity risks of complex concentrates.

Genotoxicity assessment of membrane concentrates of landfill leachate treated with Fenton reagent and UV-Fenton reagent using human hepatoma cell line

International Nuclear Information System (INIS)

Wang, Guifang; Lu, Gang; Yin, Pinghe; Zhao, Ling; Jimmy Yu, Qiming

2016-01-01

Highlights: • Membrane concentrates have a threat to human health and environment. • Untreated membrane concentrates induces cytotoxic and genotoxic to HepG2 cells. • Both methods were effective method for degradation of BPA and NP in concentrates. • Both methods were efficient in reducing genotoxic effects of concentrates. • UV-Fenton reagent had higher removal efficiency and provides toxicological safety. - Abstract: Membrane concentrates of landfill leachates contain organic and inorganic contaminants that could be highly toxic and carcinogenic. In this paper, the genotoxicity of membrane concentrates before and after Fenton and UV-Fenton reagent was assessed. The cytotoxicity and genotoxicity was determined by using the methods of methyltetrazolium (MTT), cytokinesis-block micronucleus (CBMN) and comet assay in human hepatoma cells. MTT assay showed a cytotoxicity of 75% after 24 h of exposure to the highest tested concentration of untreated concentrates, and no cytotoxocity for UV-Fenton and Fenton treated concentrates. Both CBMN and comet assays showed increased levels of genotoxicity in cells exposed to untreated concentrates, compared to those occurred in cells exposed to UV-Fenton and Fenton reagent treated concentrates. There was no significant difference between negative control and UV-Fenton treated concentrates for micronucleus and comet assay parameters. UV-Fenton and Fenton treatment, especially the former, were effective methods for degradation of bisphenol A and nonylphenol in concentrates. These findings showed UV-Fenton and Fenton reaction were effective methods for treatment of such complex concentrates, UV-Fenton reagent provided toxicological safety of the treated effluent, and the genotoxicity assays were found to be feasible tools for assessment of toxicity risks of complex concentrates.

Hexavalent Chromium Is Cytotoxic and Genotoxic to Hawksbill Sea Turtle Cells

Science.gov (United States)

Wise, Sandra S.; Xie, Hong; Fukuda, Tomokazu; Thompson, W. Douglas; Wise, John Pierce

2014-01-01

Sea turtles are a charismatic and ancient ocean species and can serve as key indicators for ocean ecosystems, including coral reefs and sea grass beds as well as coastal beaches. Genotoxicity studies in the species are absent, limiting our understanding of the impact of environmental toxicants on sea turtles. Hexavalent chromium (Cr(VI)) is a ubiquitous environmental problem worldwide, and recent studies show it is a global marine pollutant of concern. Thus, we evaluated the cytotoxicity and genotoxicity of soluble and particulate Cr(VI) in hawksbill sea turtle cells. Particulate Cr(VI) was both cytotoxic and genotoxic to sea turtle cells. Concentrations of 0.1, 0.5, 1, and 5 μg/cm2 lead chromate induced 108, 79, 54, and 7 percent relative survival, respectively. Additionally, concentrations of 0, 0.1, 0.5, 1, and 5 μg/cm2 lead chromate induced damage in 4, 10, 15, 26, and 36 percent of cells and caused 4, 11, 17, 30, and 56 chromosome aberrations in 100 metaphases, respectively. For soluble Cr, concentrations of 0.25, 0.5, 1, 2.5, and 5 μM sodium chromate induced 84, 69, 46, 25, and 3 percent relative survival, respectively. Sodium chromate induced 3, 9, 9, 14, 21, and 29 percent of metaphases with damage, and caused 3, 10, 10, 16, 26, and 39 damaged chromosomes in 100 metaphases at concentrations of 0, 0.25, 0.5, 1, 2.5, and 5 μM sodium chromate, respectively. These data suggest that Cr(VI) may be a concern for hawksbill sea turtles and sea turtles in general. PMID:24952338

Analysis of Aloe vera cytotoxicity and genotoxicity associated with endodontic medication and laser photobiomodulation.

Science.gov (United States)

Carvalho, Nayane Chagas; Guedes, Simone Alves Garcez; Albuquerque-Júnior, Ricardo Luiz Cavalcanti; de Albuquerque, Diana Santana; de Souza Araújo, Adriano Antunes; Paranhos, Luiz Renato; Camargo, Samira Esteves Afonso; Ribeiro, Maria Amália Gonzaga

2018-01-01

This study aims to evaluate, in vitro, the effect of Aloe vera associated with endodontic medication, with or without laser photobiomodulation (FTL) irradiation in FP6 human pulp fibroblasts. The materials were divided into eight groups: CTR - control; CL - FTL alone; AA - Aloe vera with distilled water; AL - Aloe vera with distilled water and FTL; HA - calcium hydroxide P.A. with distilled water; HL - calcium hydroxide P.A. with distilled water and FTL; HAA - calcium hydroxide P.A. with Aloe vera and distilled water; HAL - calcium hydroxide P.A. with Aloe vera, distilled water, and FTL. The cytotoxicity was evaluated by MTT assay at 24, 48, and 72h and the genotoxicity by micronucleus test assay. This study was performed in triplicate. Data obtained in both tests were statistically analyzed by ANOVA and Tukey's tests (p≤0.05). Group AA presented high genotoxicity and low cytotoxicity. After 24, 48, and 72h, the group HAA significantly reduced the cell viability. Interaction with FTL showed slightly increase cell viability after 24 and 48h in groups CL and HL (pAloe vera allowed higher cell viability in human pulp fibroblasts in the presence of calcium hydroxide or with FTL separately, but genotoxicity increased in these associations. Copyright © 2017 Elsevier B.V. All rights reserved.

Colon Trauma: Evidence-Based Practices.

Science.gov (United States)

Yamamoto, Ryo; Logue, Alicia J; Muir, Mark T

2018-01-01

Colon injury is not uncommon and occurs in about a half of patients with penetrating hollow viscus injuries. Despite major advances in the operative management of penetrating colon wounds, there remains discussion regarding the appropriate treatment of destructive colon injuries, with a significant amount of scientific evidence supporting segmental resection with primary anastomosis in most patients without comorbidities or large transfusion requirement. Although literature is sparse concerning the management of blunt colon injuries, some studies have shown operative decision based on an algorithm originally defined for penetrating wounds should be considered in blunt colon injuries. The optimal management of colonic injuries in patients requiring damage control surgery (DCS) also remains controversial. Studies have recently reported that there is no increased risk compared with patients treated without DCS if fascial closure is completed on the first reoperation, or that a management algorithm for penetrating colon wounds is probably efficacious for colon injuries in the setting of DCS as well.

Colonic Diverticulitis in the Elderly

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Chien-Kuo Liu

2009-03-01

Full Text Available Diverticular disease of the colon is a disease that mainly affects the elderly and presents in 50–70% of those aged 80 years or older. The most common complication is colonic diverticulitis. Eighty percent of patients who present with colonic diverticulitis are aged 50 years and older. Diagnosis and treatment of colonic diverticulitis in the elderly is more difficult and complicated owing to more comorbid conditions. Computed tomography is recommended for diagnosis when colonic diverticulitis is suspected. Most patients admitted with acute colonic diverticulitis respond to conservative treatment, but 15–30% of patients require surgery. Because surgery for acute colonic diverticulitis carries significant rates of morbidity and mortality, conservative treatment is recommended in the elderly. Conservative treatment of colonic diverticulitis with antibiotics, bowel rest, possibly including parenteral alimentation, is usually applied for 1–2 weeks. In the absence of a response to conservative treatment, frequent recurrence or complications (abscesses, fistulas, bowel obstructions, and free perforations, surgery is indicated.

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. PMID:27234561

Cyto- and genotoxic profile of groundwater used as drinking water supply before and after disinfection.

Science.gov (United States)

Pellacani, C; Cassoni, F; Bocchi, C; Martino, A; Pinto, G; Fontana, F; Furlini, M; Buschini, A

2016-12-01

The assessment of the toxicological properties of raw groundwater may be useful to predict the type and quality of tap water. Contaminants in groundwater are known to be able to affect the disinfection process, resulting in the formation of substances that are cytotoxic and/or genotoxic. Though the European directive (98/83/EC, which establishes maximum levels for contaminants in raw water (RW)) provides threshold levels for acute exposure to toxic compounds, the law does not take into account chronic exposure at low doses of pollutants present in complex mixture. The purpose of this study was to evaluate the cyto- and genotoxic load in the groundwater of two water treatment plants in Northern Italy. Water samples induced cytotoxic effects, mainly observed when human cells were treated with RW. Moreover, results indicated that the disinfection process reduced cell toxicity, independent of the biocidal used. The induction of genotoxic effects was found, in particular, when the micronucleus assay was carried out on raw groundwater. These results suggest that it is important to include bio-toxicological assays as additional parameters in water quality monitoring programs, as their use would allow the evaluation of the potential risk of groundwater for humans.

The use of genotoxicity biomarkers in molecular epidemiology: applications in environmental, occupational and dietary studies

Directory of Open Access Journals (Sweden)

Carina Ladeira

2017-08-01

Full Text Available Molecular epidemiology is an approach increasingly used in the establishment of associations between exposure to hazardous substances and development of disease, including the possible modulation by genetic susceptibility factors. Environmental chemicals and contaminants from anthropogenic pollution of air, water and soil, but also originating specifically in occupational contexts, are potential sources of risk of development of disease. Also, diet presents an important role in this process, with some well characterized associations existing between nutrition and some types of cancer. Genotoxicity biomarkers allow the detection of early effects that result from the interaction between the individual and the environment; they are therefore important tools in cancer epidemiology and are extensively used in human biomonitoring studies. This work intends to give an overview of the potential for genotoxic effects assessment, specifically with the cytokinesis blocked micronucleus assay and comet assay in environmental and occupational scenarios, including diet. The plasticity of these techniques allows their inclusion in human biomonitoring studies, adding important information with the ultimate aim of disease prevention, in particular cancer, and so it is important that they be included as genotoxicity assays in molecular epidemiology.

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.

Sensitivity of Bidens laevis L. to mutagenic compounds. Use of chromosomal aberrations as biomarkers of genotoxicity

International Nuclear Information System (INIS)

Perez, D.J.; Lukaszewicz, G.; Menone, M.L.; Camadro, E.L.

2011-01-01

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.

Critical review of the current and future challenges associated with advanced in vitro systems towards the study of nanoparticle (secondary) genotoxicity.

Science.gov (United States)

Evans, Stephen J; Clift, Martin J D; Singh, Neenu; de Oliveira Mallia, Jefferson; Burgum, Michael; Wills, John W; Wilkinson, Thomas S; Jenkins, Gareth J S; Doak, Shareen H

2017-01-01

With the need to understand the potential biological impact of the plethora of nanoparticles (NPs) being manufactured for a wide range of potential human applications, due to their inevitable human exposure, research activities in the field of NP toxicology has grown exponentially over the last decade. Whilst such increased research efforts have elucidated an increasingly significant knowledge base pertaining to the potential human health hazard posed by NPs, understanding regarding the possibility for NPs to elicit genotoxicity is limited. In vivo models are unable to adequately discriminate between the specific modes of action associated with the onset of genotoxicity. Additionally, in line with the recent European directives, there is an inherent need to move away from invasive animal testing strategies. Thus, in vitro systems are an important tool for expanding our mechanistic insight into NP genotoxicity. Yet uncertainty remains concerning their validity and specificity for this purpose due to the unique challenges presented when correlating NP behaviour in vitro and in vivo This review therefore highlights the current state of the art in advanced in vitro systems and their specific advantages and disadvantages from a NP genotoxicity testing perspective. Key indicators will be given related to how these systems might be used or improved to enhance understanding of NP genotoxicity. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society.

Evaluation of genotoxicity after application of Listerine(R) on human lymphocytes by micronucleus and single cell gel electrophoresis assays.

Science.gov (United States)

Türkez, Hasan; Togar, Basak; Arabaci, Taner

2012-04-01

Listerine (LN) is one of the most commonly used mouth rinses worldwide although very limited information is available concerning its genotoxicity. In another view, the biological safety profile of oral care products is frequently assumed on the basis of simplistic test models. Therefore, the present study was undertaken to investigate the in vitro genotoxic potential of LN using micronucleus and single cell gel electrophoresis tests as genetic endpoints. Different concentrations of LN (0-100% of ml/culture, v/v) were applied to whole human blood cultures (n = 5). The result of the present study showed that there were no statistically significant differences (p > 0.05) between the control group and the groups treated with LN alone in both analysed endpoints. In conclusion, our result first demonstrated the absence of genotoxicity of LN on human lymphocytes.

The genotoxic effect of oxcarbazepine on mice blood lymphocytes.

Science.gov (United States)

Akbar, Huma; Khan, Ajmal; Mohammadzai, Imdadullah; Khisroon, Muhammad; Begum, Ilham

2018-04-01

This study was conducted to assess the amount of DNA damage caused by Oxcarbazepine (OXC) through single cell gel electrophoresis (SCGE) technique/comet assay. OXC derived from dibenzazepine series is an effective second generation antiepileptic drug (AED) for both children and adults. Side effects like genotoxic effects of AEDs are of prime importance resulting from toxic metabolites, free radicals and reactive oxygen species (ROS). Forty Eight adult male Bagg's albino mice (BALB/c) were randomly classified into eight groups, each comprising of six animals. Two of these groups were control and six were tested groups. Control groups were injected with 1% tween 80 while tested groups were injected with 10, 20, and 40 mg/kg-day OXC for seven days (acute therapy) and 28 days (subchronic therapy) in peritoneal cavity. Blood samples were collected by cardiac puncture and subjected to comet assay for the analysis of DNA damage. Per sample 100 cells were scored and classified according to comet tail length. The results showed that OXC in acute and long term therapies had significantly higher (p < 0.05) genotoxicity in treated groups as compared to control groups. Our study suggests that OXC may cause significant DNA damage in both acute as well as in subchronic therapies.

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. Published by Elsevier Ltd.

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.

Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer research.

Science.gov (United States)

Tetteh, Paul W; Kretzschmar, Kai; Begthel, Harry; van den Born, Maaike; Korving, Jeroen; Morsink, Folkert; Farin, Henner; van Es, Johan H; Offerhaus, G Johan A; Clevers, Hans

2016-10-18

Current mouse models for colorectal cancer often differ significantly from human colon cancer, being largely restricted to the small intestine. Here, we aim to develop a colon-specific inducible mouse model that can faithfully recapitulate human colon cancer initiation and progression. Carbonic anhydrase I (Car1) is a gene expressed uniquely in colonic epithelial cells. We generated a colon-specific inducible Car1 CreER knock-in (KI) mouse with broad Cre activity in epithelial cells of the proximal colon and cecum. Deletion of the tumor suppressor gene Apc using the Car1 CreER KI caused tumor formation in the cecum but did not yield adenomas in the proximal colon. Mutation of both Apc and Kras yielded microadenomas in both the cecum and the proximal colon, which progressed to macroadenomas with significant morbidity. Aggressive carcinomas with some invasion into lymph nodes developed upon combined induction of oncogenic mutations of Apc, Kras, p53, and Smad4 Importantly, no adenomas were observed in the small intestine. Additionally, we observed tumors from differentiated Car1-expressing cells with Apc/Kras mutations, suggesting that a top-down model of intestinal tumorigenesis can occur with multiple mutations. Our results establish the Car1 CreER KI as a valuable mouse model to study colon-specific tumorigenesis and metastasis as well as cancer-cell-of-origin questions.

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.

Transverse loop colostomy and colonic motility.

Science.gov (United States)

Pucciani, F; Ringressi, M N; Maltinti, G; Bechi, P

2014-11-01

The motility of the defunctionalized colon, distal to transverse loop colostomy, has never been studied "in vivo." The aim of our study was to evaluate the influence of transverse loop colostomy on colonic motility. Thirteen patients were examined before stoma closure by means of clinical evaluation and colonic manometry; we studied both the right and distal colon in both fasting and fed patients in order to detect motor activity. Quantitative and qualitative manometric analyses showed that the diverted colon had motor activity even if no regular colonic motor pattern was observed. The spreading of aboral propagated contractions (PCs) was sometimes recorded from the right colon to the distal colon. The response of the proximal and distal colon to a standard meal, when compared to fasting values, increased more than 40 and 35 %, respectively. Stool and gas ejections from the colostomy were never related to a particular type of colonic motility: Motor quiescence such as PCs was chaotically related to stool escape. In conclusion, motility of the defunctionalized colon is preserved in patients with transverse loop colostomy.

Percutaneous drainage of colonic diverticular abscess: is colon resection necessary?

Science.gov (United States)

Gaertner, Wolfgang B; Willis, David J; Madoff, Robert D; Rothenberger, David A; Kwaan, Mary R; Belzer, George E; Melton, Genevieve B

2013-05-01

Recurrent diverticulitis has been reported in up to 30% to 40% of patients who recover from an episode of colonic diverticular abscess, so elective interval resection is traditionally recommended. The aim of this study was to review the outcomes of patients who underwent percutaneous drainage of colonic diverticular abscess without subsequent operative intervention. This was an observational study. This investigation was conducted at a tertiary care academic medical center and a single-hospital health system. Patients treated for symptomatic colonic diverticular abscess from 2002 through 2007 were included. The primary outcomes measured were complications, recurrence, and colectomy-free survival. Two hundred eighteen patients underwent percutaneous drainage of colonic diverticular abscesses. Thirty-two patients (15%) did not undergo subsequent colonic resection. Abscess location was pelvic (n = 9) and paracolic (n = 23), the mean abscess size was 4.2 cm, and the median duration of percutaneous drainage was 20 days. The comorbidities of this group of patients included severe cardiac disease (n = 16), immunodeficiency (n = 7), and severe pulmonary disease (n = 6). Freedom from recurrence at 7.4 years was 0.58 (95% CI 0.42-0.73). All recurrences were managed nonoperatively. Recurrence was significantly associated with an abscess size larger than 5 cm. Colectomy-free survival at 7.4 years was 0.17 (95% CI 0.13-0.21). This study was limited by its retrospective, nonexperimental design and short follow-up. In selected patients, observation after percutaneous drainage of colonic diverticular abscess appears to be a safe and low-risk management option.

GENOTOXICITY OF BIOREMEDIATED SOILS FROM THE REILLY TARSITE, ST. LOUIS PARK, MINNESOTA

Science.gov (United States)

An in vitro approach was used to measure the genotoxicity of creosote-contaminated soil before and after four bioremediation processes. The soil was taken from the Reilly Tar site, a closed Superfund site in Saint Louis Park, Minnesota. The creosote soil was bioremediated in bios...

Laparoscopic colectomy for transverse colon carcinoma.

Science.gov (United States)

Zmora, O; Bar-Dayan, A; Khaikin, M; Lebeydev, A; Shabtai, M; Ayalon, A; Rosin, D

2010-03-01

Laparoscopic resection of transverse colon carcinoma is technically demanding and was excluded from most of the large trials of laparoscopic colectomy. The aim of this study was to assess the safety, feasibility, and outcome of laparoscopic resection of carcinoma of the transverse colon. A retrospective review was performed to identify patients who underwent laparoscopic resection of transverse colon carcinoma. These patients were compared to patients who had laparoscopic resection for right and sigmoid colon carcinoma. In addition, they were compared to a historical series of patients who underwent open resection for transverse colon cancer. A total of 22 patients underwent laparoscopic resection for transverse colon carcinoma. Sixty-eight patients operated for right colon cancer and 64 operated for sigmoid colon cancer served as comparison groups. Twenty-four patients were identified for the historical open group. Intraoperative complications occurred in 4.5% of patients with transverse colon cancer compared to 5.9% (P = 1.0) and 7.8% (P = 1.0) of patients with right and sigmoid colon cancer, respectively. The early postoperative complication rate was 45, 50 (P = 1.0), and 37.5% (P = 0.22) in the three groups, respectively. Conversion was required in 1 (5%) patient in the laparoscopic transverse colon group. The conversion rate and late complications were not significantly different in the three groups. There was no significant difference in the number of lymph nodes harvested in the laparoscopic and open groups. Operative time was significantly longer in the laparoscopic transverse colectomy group when compared to all other groups (P = 0.001, 0.008, and transverse colectomy, respectively). The results of laparoscopic colon resection for transverse colon carcinoma are comparable to the results of laparoscopic resection of right or sigmoid colon cancer and open resection of transverse colon carcinoma. These results suggest that laparoscopic resection of transverse

Genotoxic and Antigenotoxic Potential of Momordica charantia Linn (Cucurbitaceae) in the Wing Spot Test of Drosophila melanogaster.

Science.gov (United States)

Guterres, Zaira Rosa; Zanetti, Thalita Alves; Sennes-Lopes, Tiago Felipe; da Silva, Ana Francisca Gomes

2015-10-01

Momordica charantia, popularly known as bitter melon, is a plant widely used in ethnobotanical medicine. It has antibacterial, antifungal, anthelmintic, antidiabetic, antiviral, and antimalarial activities, among others. The goal of this study was to evaluate the genotoxic and/or antigenotoxic activity of the aqueous extracts obtained from the aerial parts and fruit of this plant by means of the Drosophila melanogaster wing spot test. Third-stage larvae that obtained standard (ST) cross and high bioactivation (HB) cross were treated with aqueous extracts of the aerial parts (IQA) and fruit (IQF) of M. charantia, following two protocols (genotoxicity and antigenotoxicity). The aqueous extracts are not genotoxic in lower concentrations. The frequencies of mutant spots observed in the descendants of the ST and HB crosses treated with doxorubicin (DXR) alone were 8.65 and 9.25, respectively, whereas in those cotreated with IQA and DXR, the frequencies ranged from 15.90 to 29 in the ST cross and from 15.05 to 24.78 in the HB cross. In cotreatment with IQF, the frequencies ranged from 30.10 to 30.65 in the ST cross and from 13.60 to 14.50 in the HB cross, whereas the frequencies obtained with DXR were 32.50 in the ST cross and 26.00 in the HB cross. In conclusion, the IQA has a synergistic effect, enhancing the genotoxicity of DXR in the ST cross and the HB cross, whereas the IQF has antigenotoxic effects in the HB cross.

Primary encopresis: evaluation and treatment.

Science.gov (United States)

O'Brien, S; Ross, L V; Christophersen, E R

1986-01-01

Cathartic and behavioral treatment procedures for eliminating diurnal and nocturnal primary encopresis were investigated using a multiple-baseline design across four children. The dependent and independent variables measured were appropriate bowel movements, soiling accidents, independent toiletings, and cathartic use. Over 177 reliability observations (home visits) were conducted. For two of the children, treatment with cathartics and child-time remedied their soiling accidents and increased their independent toiletings in 8 to 11 weeks. While the cathartics and child-time increased the rate of appropriate bowel movements, they did not eliminate the soiling accidents with the other two children. Independent toiletings for these two children were achieved after 32 to 39 weeks of treatment when punishment procedures (positive practice, time-out, and hourly toilet sits) were incorporated and the suppositories were faded systematically. PMID:3733585

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 ...

Role of Proteus mirabilis MR/P fimbriae and flagella in adhesion, cytotoxicity and genotoxicity induction in T24 and Vero cells.

Science.gov (United States)

Scavone, Paola; Villar, Silvia; Umpiérrez, Ana; Zunino, Pablo

2015-06-01

Proteus mirabilis is frequently associated with complicated urinary tract infections (UTI). It is proposed that several virulence factors are associated with P. mirabilis uropathogenicity. The aim of this work was to elucidate genotoxic and cytotoxic effects mediated by MR/P fimbriae and flagella in eukaryotic cells in vitro. Two cell lines (kidney- and bladder-derived) were infected with a clinical wild-type P. mirabilis strain and an MR/P and a flagellar mutant. We evaluated adhesion, genotoxicity and cytotoxicity by microscopy, comet assay and triple staining technique, respectively. Mutant strains displayed lower adhesion rates than the P. mirabilis wild-type strain and were significantly less effective to induce genotoxic and cytotoxic effects compared to the wild type. We report for the first time that P. mirabilis MR/P fimbriae and flagella mediate genotoxic and cytotoxic effects on eukaryotic cells, at least in in vitro conditions. These results could contribute to design new strategies for the control of UTI. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Colon and rectal cancer survival by tumor location and microsatellite instability: the Colon Cancer Family Registry.

Science.gov (United States)

Phipps, Amanda I; Lindor, Noralane M; Jenkins, Mark A; Baron, John A; Win, Aung Ko; Gallinger, Steven; Gryfe, Robert; Newcomb, Polly A

2013-08-01

Cancers in the proximal colon, distal colon, and rectum are frequently studied together; however, there are biological differences in cancers across these sites, particularly in the prevalence of microsatellite instability. We assessed the differences in survival by colon or rectal cancer site, considering the contribution of microsatellite instability to such differences. This is a population-based prospective cohort study for cancer survival. This study was conducted within the Colon Cancer Family Registry, an international consortium. Participants were identified from population-based cancer registries in the United States, Canada, and Australia. Information on tumor site, microsatellite instability, and survival after diagnosis was available for 3284 men and women diagnosed with incident invasive colon or rectal cancer between 1997 and 2002, with ages at diagnosis ranging from 18 to 74. Cox regression was used to calculate hazard ratios for the association between all-cause mortality and tumor location, overall and by microsatellite instability status. Distal colon (HR, 0.59; 95% CI, 0.49-0.71) and rectal cancers (HR, 0.68; 95% CI, 0.57-0.81) were associated with lower mortality than proximal colon cancer overall. Compared specifically with patients with proximal colon cancer exhibiting no/low microsatellite instability, patients with distal colon and rectal cancers experienced lower mortality, regardless of microsatellite instability status; patients with proximal colon cancer exhibiting high microsatellite instability had the lowest mortality. Study limitations include the absence of stage at diagnosis and cause-of-death information for all but a subset of study participants. Some patient groups defined jointly by tumor site and microsatellite instability status are subject to small numbers. Proximal colon cancer survival differs from survival for distal colon and rectal cancer in a manner apparently dependent on microsatellite instability status. These

Pre-and post-gamma irradiation fetal bovine serum genotoxic evaluation

International Nuclear Information System (INIS)

Pilili, J.P.; Molinari, G.; Gonzalez, N.V.; Soloneski, S.; Reigosa, M.L.; Larramendy, M.L.

2008-01-01

Fetal bovine serum (FBS) is an essential component to propagate cells in vitro. Different methods are used by the industry to eliminate xenobiotic agents before their use, among them the ionizing radiations application. The aim of the present work was to analyze the existence of xenobiotic agents in 18 FBS lots manufactured by Internegocios S.A., Mercedes, Pcia. Bs. As., assessed pre- and postirradiation. The analysis of the frequency of sister chromatid exchanges (SCEs) and micronuclei (MNs) in CHO K1 cells were used as genotoxicity endpoints. The results showed SCEs increase in 44% of the lots (71% of non-irradiated sera and 29% of irradiated sera) and in MNs only in a sample non-irradiated (6.25%). These results would render evident the presence of agents with genotoxic capacity as much in lots of FBS irradiated as in non-irradiated. Thus, the irradiation not only grants sterility to FBS but eliminates or inhibits those xenobiotics with deleterious capacity present in them before irradiation. Finally, variations in the conditions during irradiation (temperature, time of exposure) could generate compound with clastogenic and/or aneugenic capacity that could affect the correct propagation of cells in culture. (authors)

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.

Comparative study of the mutagenic and genotoxic activity associated with inhalable particulate matter in Rio de Janeiro air

Energy Technology Data Exchange (ETDEWEB)

Miguel, A.G.; Daisey, J.M.; Sousa, J.A. (Federal Univ. of Rio de Janeiro (Brazil))

1990-01-01

We have determined the genotoxic and mutagenic activities associated with inhalable particulate matter (IPM) collected in Rio de Janeiro, Brazil, Camden, NJ, and Caldecott Tunnel, CA, and used these results to compare three different bioassays. Samples collected every 12 hr (Rio) or every 24 hr (Camden) were extracted sequentially with cyclohexane (CX), dichloromethane (DCM), and acetone (ACE), for a rough fractionation by polarity, and composites of the extracts were tested for mutagenicity using the Salmonella frame shift (TA98) and base substitution (TA100) tester strains, as well as for genotoxicity using the Rossman Microscreen bioassay based on the induction of lambda-prophage in a lysogenic Escherichia coli strain. All samples were tested without and with S9 metabolic activation. Maximum mutagenic and genotoxic activities were in the nonpolar (CX) and polar (ACE) fractions, respectively, indicating that these two assays detect different classes of compounds with different efficiencies. Oxidative aging of the Rio aerosol is indicated by a shift in activities in both tests from the less polar fractions in the day to the polar (ACE) fraction at night. The Rio TA98 mutagenic (18 rev/m3) and genotoxic (1.4 x 10(5) PFU/m3) activities were higher than those for Camden, an Eastern U.S. city, by factors of 1.4 and 2.8, respectively.

No evidence of the genotoxic potential of gold, silver, zinc oxide and titanium dioxide nanoparticles in the SOS chromotest.

Science.gov (United States)

Nam, Sun-Hwa; Kim, Shin Woong; An, Youn-Joo

2013-10-01

Gold nanoparticles (Au NPs), silver nanoparticles (Ag NPs), zinc oxide nanoparticles (ZnO NPs) and titanium dioxide nanoparticles (TiO2 NPs) are widely used in cosmetic products such as preservatives, colorants and sunscreens. This study investigated the genotoxicity of Au NPs, Ag NPs, ZnO NPs and TiO2 NPs using the SOS chromotest with Escherichia coli PQ37. The maximum exposure concentrations for each nanoparticle were 3.23 mg l(-1) for Au NPs, 32.3 mg l(-1) for Ag NPs and 100 mg l(-1) for ZnO NPs and TiO2 NPs. Additionally, in order to compare the genotoxicity of nanoparticles and corresponding dissolved ions, the ions were assessed in the same way as nanoparticles. The genotoxicity of the titanium ion was not assessed because of the extremely low solubility of TiO2 NPs. Au NPs, Ag NPs, ZnO NPs, TiO2 NPs and ions of Au, Ag and Zn, in a range of tested concentrations, exerted no effects in the SOS chromotest, evidenced by maximum IF (IFmax) values of below 1.5 for all chemicals. Owing to the results, nanosized Au NPs, Ag NPs, ZnO NPs, TiO2 NPs and ions of Au, Ag and Zn are classified as non-genotoxic on the basis of the SOS chromotest used in this study. To the best of our knowledge, this is the first study to evaluate the genotoxicity of Au NPs, Ag NPs, ZnO NPs and TiO2 NPs using the SOS chromotest. Copyright © 2012 John Wiley & Sons, Ltd.

Sex-related effects of imidacloprid modulated by piperonyl butoxide and menadione in rats. Part II: genotoxic and cytotoxic potential.

Science.gov (United States)

Arslan, Mehmet; Sevgiler, Yusuf; Buyukleyla, Mehmet; Yardimci, Mustafa; Yilmaz, Mehmet; Rencuzogullari, Eyyup

2016-01-01

Despite its intended use, imidacloprid causes genotoxic and cytotoxic effects in mammals, especially in the presence of metabolic activation systems. The aim of this study was to determine to which extent these effects are sex related and how its metabolism modulators piperonyl butoxide and menadione affect its toxicity. Male and female Sprague-Dawley rats were injected with the intraperitoneal LD50 dose of imidacloprid alone (170 mg/kg) or pretreated with piperonyl butoxide (100 mg/kg) and menadione (25 mg/kg) for 12 and 24 h. Structural chromosome aberrations, abnormal cells and mitotic index were determined microscopically in bone marrow cells. Male rats showed susceptibility to the genotoxic effects of imidacloprid. Piperonyl butoxide was effective in countering this effect only at 24 h, whereas menadione exacerbated imidacloprid-induced genotoxicity. Piperonyl butoxide and menadione pretreatments increased the percentage of structural chromosome aberrations and abnormal cells in females. Imidacloprid decreased the mitotic index, whereas pretreatment with piperonyl butoxide and menadione showed improvement in both sexes. We believe that CYP450-mediated metabolism of imidacloprid is under the hormonal control and therefore that its genotoxicity is sex related. Piperonyl butoxide pretreatment also showed sex-related modulation. The hormonal effects on imidacloprid biotransformation require further investigation.

Efficacy of Allium cepa test system for screening cytotoxicity and genotoxicity of industrial effluents originated from different industrial activities.

Science.gov (United States)

Pathiratne, Asoka; Hemachandra, Chamini K; De Silva, Nimal

2015-12-01

Efficacy of Allium cepa test system for screening cytotoxicity and genotoxicity of treated effluents originated from four types of industrial activities (two textile industries, three rubber based industries, two common treatment plants of industrial zones, and two water treatment plants) was assessed. Physico-chemical parameters including the heavy metal/metalloid levels of the effluents varied depending on the industry profile, but most of the measured parameters in the effluents were within the specified tolerance limits of Sri Lankan environmental regulations for discharge of industrial effluents into inland surface waters. In the A. cepa test system, the undiluted effluents induced statistically significant root growth retardation, mitosis depression, and chromosomal aberrations in root meristematic cells in most cases in comparison to the dilution water and upstream water signifying effluent induced cytotoxicity and genotoxicity. Ethyl methane sulphonate (a mutagen, positive control) and all the effluents under 1:8 dilution significantly induced total chromosomal aberrations in root meristematic cells in comparison to the dilution water and upstream water indicating inadequacy of expected 1:8 dilutions in the receiving waters for curtailing genotoxic impacts. The results support the use of a practically feasible A. cepa test system for rapid screening of cytotoxicity and genotoxicity of diverse industrial effluents discharging into inland surface waters.

Silica nanoparticles and biological dispersants: genotoxic effects on A549 lung epithelial cells

International Nuclear Information System (INIS)

Brown, David M.; Varet, Julia; Johnston, Helinor; Chrystie, Alison; Stone, Vicki

2015-01-01

Silica nanoparticle exposure could be intentional (e.g. medical application or food) or accidental (e.g. occupational inhalation). On entering the body, particles become coated with specific proteins depending on the route of entry. The ability of silica particles of different size and charge (non-functionalized 50 and 200 nm and aminated 50 and 200 nm) to cause genotoxic effects in A549 lung epithelial cells was investigated. Using the modified comet assay and the micronucleus assay, we examined the effect of suspending the particles in different dispersion media [RPMI or Hanks’ balanced salt solution (HBSS), supplemented with bovine serum albumin (BSA), lung lining fluid (LLF) or serum] to determine if this influenced the particle’s activity. Particle characterisation suggested that the particles were reasonably well dispersed in the different media, with the exception of aminated 50 nm particles which showed evidence of agglomeration. Plain 50, 200 nm and aminated 50 nm particles caused significant genotoxic effects in the presence of formamidopyrimidine-DNA glycosylase when dispersed in HBSS or LLF. These effects were reduced when the particles were dispersed in BSA and serum. There was no significant micronucleus formation produced by any of the particles when suspended in any of the dispersants. The data suggest that silica particles can produce a significant genotoxic effect according to the comet assay in A549 cells, possibly driven by an oxidative stress-dependent mechanism which may be modified depending on the choice of dispersant employed

Silica nanoparticles and biological dispersants: genotoxic effects on A549 lung epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Brown, David M., E-mail: d.brown@hw.ac.uk [Heriot-Watt University, Nanosafety Research Group, School of Life Sciences (United Kingdom); Varet, Julia, E-mail: julia.varet@IOM-world.org [Institute of Occupational Medicine (United Kingdom); Johnston, Helinor, E-mail: h.johnston@hw.ac.uk; Chrystie, Alison; Stone, Vicki, E-mail: v.stone@hw.ac.uk [Heriot-Watt University, Nanosafety Research Group, School of Life Sciences (United Kingdom)

2015-10-15

Silica nanoparticle exposure could be intentional (e.g. medical application or food) or accidental (e.g. occupational inhalation). On entering the body, particles become coated with specific proteins depending on the route of entry. The ability of silica particles of different size and charge (non-functionalized 50 and 200 nm and aminated 50 and 200 nm) to cause genotoxic effects in A549 lung epithelial cells was investigated. Using the modified comet assay and the micronucleus assay, we examined the effect of suspending the particles in different dispersion media [RPMI or Hanks’ balanced salt solution (HBSS), supplemented with bovine serum albumin (BSA), lung lining fluid (LLF) or serum] to determine if this influenced the particle’s activity. Particle characterisation suggested that the particles were reasonably well dispersed in the different media, with the exception of aminated 50 nm particles which showed evidence of agglomeration. Plain 50, 200 nm and aminated 50 nm particles caused significant genotoxic effects in the presence of formamidopyrimidine-DNA glycosylase when dispersed in HBSS or LLF. These effects were reduced when the particles were dispersed in BSA and serum. There was no significant micronucleus formation produced by any of the particles when suspended in any of the dispersants. The data suggest that silica particles can produce a significant genotoxic effect according to the comet assay in A549 cells, possibly driven by an oxidative stress-dependent mechanism which may be modified depending on the choice of dispersant employed.

Silica nanoparticles and biological dispersants: genotoxic effects on A549 lung epithelial cells

Science.gov (United States)

Brown, David M.; Varet, Julia; Johnston, Helinor; Chrystie, Alison; Stone, Vicki

2015-10-01

Silica nanoparticle exposure could be intentional (e.g. medical application or food) or accidental (e.g. occupational inhalation). On entering the body, particles become coated with specific proteins depending on the route of entry. The ability of silica particles of different size and charge (non-functionalized 50 and 200 nm and aminated 50 and 200 nm) to cause genotoxic effects in A549 lung epithelial cells was investigated. Using the modified comet assay and the micronucleus assay, we examined the effect of suspending the particles in different dispersion media [RPMI or Hanks' balanced salt solution (HBSS), supplemented with bovine serum albumin (BSA), lung lining fluid (LLF) or serum] to determine if this influenced the particle's activity. Particle characterisation suggested that the particles were reasonably well dispersed in the different media, with the exception of aminated 50 nm particles which showed evidence of agglomeration. Plain 50, 200 nm and aminated 50 nm particles caused significant genotoxic effects in the presence of formamidopyrimidine-DNA glycosylase when dispersed in HBSS or LLF. These effects were reduced when the particles were dispersed in BSA and serum. There was no significant micronucleus formation produced by any of the particles when suspended in any of the dispersants. The data suggest that silica particles can produce a significant genotoxic effect according to the comet assay in A549 cells, possibly driven by an oxidative stress-dependent mechanism which may be modified depending on the choice of dispersant employed.

Hexavalent chromium is cytotoxic and genotoxic to hawksbill sea turtle cells

Energy Technology Data Exchange (ETDEWEB)

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

2014-09-01

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

Hexavalent chromium is cytotoxic and genotoxic to hawksbill sea turtle cells

International Nuclear Information System (INIS)

Wise, Sandra S.; Xie, Hong; Fukuda, Tomokazu; Douglas Thompson, W.

2014-01-01

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

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....... Croix. Thus, when the Lincoln administration seriously considered colonization plans in 1862, Danish Charge d’Affaires Waldemar Raasløff offered free transport for freedmen to the Caribbean island, where there was a “distinct lack of laborers.” As a small first step towards colonization, Denmark...

Involvement of mismatch repair proteins in adaptive responses induced by N-methyl-N'-nitro-N-nitrosoguanidine against {gamma}-induced genotoxicity in human cells

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, Ayumi; Sakamoto, Yasuteru; Masumura, Kenichi; Honma, Masamitsu [Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan); Nohmi, Takehiko, E-mail: nohmi@nihs.go.jp [Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan)

2011-08-01

Highlights: {yields} Health effects of radiation should be evaluated in combination with chemicals. {yields} Here, we show that MNNG suppresses radiation-induced genotoxicity in human cells. {yields} Mismatch repair proteins play critical roles in the apparent adaptive responses. {yields} Chemical exposure may modulate radiation-induced genotoxicity in humans. - Abstract: As humans are exposed to a variety of chemical agents as well as radiation, health effects of radiation should be evaluated in combination with chemicals. To explore combined genotoxic effects of radiation and chemicals, we examined modulating effects of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a direct-acting methylating agent, against genotoxicity of {gamma}-radiation. Human lymphoblastoid TK6 cells and its mismatch-deficient derivative, i.e., MT1 cells, were treated with MNNG for 24 h before they were exposed to {gamma}-irradiation at a dose of 1.0 Gy, and the resulting genotoxicity was examined. In TK6 cells, the pretreatments with MNNG at low doses suppressed frequencies of the thymidine kinase (TK) gene mutation and micronucleus (MN) formation induced by {gamma}-irradiation and thus the dose responses of TK and MN assays were U-shaped along with the pretreatment doses of MNNG. In contrast, the genotoxic effects of MNNG and {gamma}-irradiation were additive in MT1 cells and the frequencies of TK mutations and MN induction increased along with the doses of MNNG. Apoptosis induced by {gamma}-radiation was suppressed by the pretreatments in TK6 cells, but not in MT1 cells. The expression of p53 was induced and cell cycle was delayed at G2/M phase in TK6, but not in MT1 cells, by the treatments with MNNG. These results suggest that pretreatments of MNNG at low doses suppress genotoxicity of {gamma}-radiation in human cells and also that mismatch repair proteins are involved in the apparent adaptive responses.

Comparative cytotoxic and genotoxic potential of 13 drinking water disinfection by-products using a microplate-based cytotoxicity assay and a developed SOS/umu assay.

Science.gov (United States)

Zhang, Shao-Hui; Miao, Dong-Yue; Tan, Li; Liu, Ai-Lin; Lu, Wen-Qing

2016-01-01

The implications of disinfection by-products (DBPs) present in drinking water are of public health concern because of their potential mutagenic, carcinogenic and other toxic effects on humans. In this study, we selected 13 main DBPs found in drinking water to quantitatively analyse their cytotoxicity and genotoxicity using a microplate-based cytotoxicity assay and a developed SOS/umu assay in Salmonella typhimurium TA1535/pSK1002. With the developed SOS/umu test, eight DBPs: 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-fura3-chloro-4-(dichloromethyl)-5-hydroxy-2-[5H]-furanone (MX), dibromoacetonitrile (DBN), iodoacetic acid (IA), bromochloroacetonitrile (BCN), bromoacetic acid (BA), trichloroacetonitrile (TCN), dibromoacetic acid (DBA) and dichloroacetic acid (DCA) were significantly genotoxic to S. typhimurium. Three DBPs: chloroacetic acid (CA), trichloroacetic acid (TCA) and dichloroacetonitrile (DCN) were weakly genotoxic, whereas the remaining DBPs: chloroacetonitrile (CN) and chloral hydrate (CH) were negative. The rank order in decreasing genotoxicity was as follows: MX > DBN > IA > BCN > BA > TCN > DBA > DCA > CA, TCA, DCN > CN, CH. MX was approximately 370 000 times more genotoxic than DCA. In the microplate-based cytotoxicity assay, cytotoxic potencies of the 13 DBPs were compared and ranked in decreasing order as follows: MX > IA > DBN > BCN > BA > TCN > DCN > CA > DCA > DBA > CN > TCA > CH. MX was approximately 19 200 times more cytotoxic than CH. A statistically significant correlation was found between cytotoxicity and genotoxicity of the 13 DBPs in S. typhimurium. Results suggest that microplate-based cytotoxicity assay and the developed SOS/umu assay are feasible tools for analysing the cytotoxicity and genotoxicity of DBPs, particularly for comparing their toxic intensities quantitatively. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e

Does the recommended lymphocyte cytokinesis-block micronucleus assay for human biomonitoring actually detect DNA damage induced by occupational and environmental exposure to genotoxic chemicals?

Science.gov (United States)

Speit, Günter

2013-07-01

This commentary challenges the paradigm that the cytokinesis-block micronucleus assay (CBMN assay) with cultured human lymphocytes, as it is performed currently, is a sensitive and useful tool for detecting genotoxic effects in populations exposed occupationally or environmentally to genotoxic chemicals. Based on the principle of the assay and the available data, increased micronucleus (MN) frequencies in binucleated cells (BNC) are mainly due to MN produced in vitro during the cultivation period (i.e. MN produced in vivo do not substantially contribute to the MN frequency measured in BNC). The sensitivity of the assay for the detection of induced MN in BNC after an in vivo exposure to a genotoxic chemical is limited because cytochalasin B (Cyt-B) is added relatively late during the culture period and, therefore, the BNC that are scored do not always represent cells that have completed one cell cycle only. Furthermore, this delay means that damaged cells can be eliminated by apoptosis and/or that DNA damage induced in vivo can be repaired prior to the production of a MN in the presence of Cyt-B. A comparison with the in vitro CBMN assay used for genotoxicity testing leads to the conclusion that it is highly unlikely that DNA damage induced in vivo is the cause for increased MN frequencies in BNC after occupational or environmental exposure to genotoxic chemicals. This commentary casts doubt on the usefulness of the CBMN assay as an indicator of genotoxicity in human biomonitoring and questions the relevance of many published data for hazard identification and risk assessment. Thus, it seems worthwhile to reconsider the use of the CBMN assay as presently conducted for the detection of genotoxic exposure in human biomonitoring.

Genotoxicity and antigenotoxicity study of aqueous and hydro-methanol extracts of Spondias mombin L., Nymphaea lotus L. and Luffa cylindrical L. using animal bioassays.

Science.gov (United States)

Oyeyemi, Ifeoluwa Temitayo; Yekeen, Olaide Maruf; Odusina, Paul Olayinka; Ologun, Taiwo Mary; Ogbaide, Orezimena Michelle; Olaleye, Olayinka Israel; Bakare, Adekunle A

2015-12-01

Spondias mombin (Linn), Nymphaea lotus (Linn) and Luffa cylindrica (Linn) (syn Luffa aegyptiaca Mill) are plants traditionally used as food ingredients and in the management of diseases, including cancer, in Nigeria. Despite the therapeutic potentials attributed to these plants, reports on their genotoxicity are scanty. In this study, the genotoxicity of the aqueous and hydro-methanol extract of these plants was evaluated using mouse bone marrow micronucleus and sperm morphology assays. Antigenotoxicity was assessed by the bone marrow micronucleus test. The highest attainable dose of 5 000 mg/kg according to OECD guidelines was first used to assess acute toxicity of the aqueous and hydro-methanol extracts in Swiss albino mice. For each extract, there were five groups of mice (n=4/group) treated with different concentrations of the extract as against the negative and positive control group for the genotoxicity study. In the antigenotoxicity study, five groups of mice were exposed to five different concentrations of the extracts along with 60 mg/kg of methyl methane sulfonate (MMS), which was used to induce genotoxicity. The mice were administered 0.2 mL of extract per day for 10 days in the genotoxicity and antigenotoxicity groups. Administration of each of the extracts at the concentration of 5 000 mg/kg did not induce acute toxicity in mice. At the concentrations tested, all the extracts, except aqueous S. mombin, increased micronucleated polychromatic erythrocytes. The aqueous and hydro-methanol extracts of N. lotus increased the frequency of aberrant sperm cells. All the extracts were also able to ameliorate MMS induced genotoxicity in bone marrow cells of the exposed mice. The results showed the potential of the extracts to induce somatic and germ cell mutation in male mice. The extracts also ameliorated the genotoxic effect of MMS.

Genotoxicity and antigenotoxicity study of aqueous and hydro-methanol extracts of Spondias mombin L., Nymphaea lotus L. and Luffa cylindrical L. using animal bioassays

Directory of Open Access Journals (Sweden)

Oyeyemi Ifeoluwa Temitayo

2015-12-01

Full Text Available Spondias mombin (Linn, Nymphaea lotus (Linn and Luffa cylindrica (Linn (syn Luffa aegyptiaca Mill are plants traditionally used as food ingredients and in the management of diseases, including cancer, in Nigeria. Despite the therapeutic potentials attributed to these plants, reports on their genotoxicity are scanty. In this study, the genotoxicity of the aqueous and hydro-methanol extract of these plants was evaluated using mouse bone marrow micronucleus and sperm morphology assays. Antigenotoxicity was assessed by the bone marrow micronucleus test. The highest attainable dose of 5 000 mg/kg according to OECD guidelines was first used to assess acute toxicity of the aqueous and hydro-methanol extracts in Swiss albino mice. For each extract, there were five groups of mice (n=4/group treated with different concentrations of the extract as against the negative and positive control group for the genotoxicity study. In the antigenotoxicity study, five groups of mice were exposed to five different concentrations of the extracts along with 60 mg/kg of methyl methane sulfonate (MMS, which was used to induce genotoxicity. The mice were administered 0.2 mL of extract per day for 10 days in the genotoxicity and antigenotoxicity groups. Administration of each of the extracts at the concentration of 5 000 mg/kg did not induce acute toxicity in mice. At the concentrations tested, all the extracts, except aqueous S. mombin, increased micronucleated polychromatic erythrocytes. The aqueous and hydro-methanol extracts of N. lotus increased the frequency of aberrant sperm cells. All the extracts were also able to ameliorate MMS induced genotoxicity in bone marrow cells of the exposed mice. The results showed the potential of the extracts to induce somatic and germ cell mutation in male mice. The extracts also ameliorated the genotoxic effect of MMS.

Prophylactic role of some plants and phytochemicals against radio-genotoxicity in human lymphocytes

Directory of Open Access Journals (Sweden)

Mohsen Cheki

2016-01-01

Full Text Available Genotoxicity in lymphocytes of cancer patients undergoing radiotherapy can lead to lymphocytopenia. Lymphocytopenia induced by radiotherapy is one of the most unfavorable prognostic biological markers in cancer patients, since it has been accepted to be associated with poor prognosis in terms of both survival time and response to cancer therapy. Therefore, reduction in lymphocytopenia may increase treatment efficiency. Research endeavors with synthetic radioprotectors in the past have met with little success primarily due to toxicity-related problems. These disadvantages have led to interest on the use of some plants and phytochemicals as radioprotector. The aim of this paper is to review protective role of some plants and phytochemicals against genotoxicity-induced by ionizing radiation in human blood lymphocytes. Therefore, current review may help the future researches to decrease lymphocytopenia in radiotherapeutic clinical trials.

The role of natural indigo dye in alleviation of genotoxicity of sodium dithionite as a reducing agent.

Science.gov (United States)

Bektaş, İdris; Karaman, Şengül; Dıraz, Emel; Çelik, Mustafa

2016-12-01

Indigo blue is a natural dye used for thousands of years by civilizations to dye fabric blue and it is naturally obtained from Isatis tinctoria. I. tinctoria is not only used for extraction of indigo blue color but also used medicinally in Traditional Chinese Medicine because of its active compounds. Sodium dithionite (Na 2 S 2 O 4 ) is used in dye bath for indigo blue extraction, but this reducing agent and its derivatives are major pollutants of textile industry and subsequently have hazardous influences on public health. Herein, the present study was designed to obtain the high yield of natural indigo dye but with low possible toxic effect. In this context, genotoxic effects of particular combinations of natural dye solutions obtained from Isatis tinctoria subsp. tomentolla with Na 2 S 2 O 4 as reducing agent were investigated. Dye solutions were obtained using two different pH levels (pH 9 and 11) and three different concentrations of Na 2 S 2 O 4 (2.5, 5 and 10 mg/ml). In addition to the dye solutions and reducing agent, aqueous extracts of I. tinctoria were assessed for their genotoxicity on human lymphocytes. For in vitro testing of genotoxicity, chromosomal aberrations (CAs), sister chromatid exchanges (SCEs) and mitotic indexes (MI) assays were used. Accordingly, Na 2 S 2 O 4 caused significant increases in CA and SCE as well decrease in MI but the genotoxic effects of sodium dithionite were reduced with natural indigo dye. As a result, aqueous extracts of Isatis leaves removed the toxic effects of sodium dithionite and showed anti-genotoxic effect. For the optimal and desired quality but with less toxic effects of natural dye, 2.5 mg/ml (for wool yarn) and 5 mg/ml (for cotton yarn) of Na 2 S 2 O 4 doses were found to be the best doses for reduction in the dye bath at Ph 9.

MALToma of the Transverse colon, Ascending colon and Caecum: A ...

African Journals Online (AJOL)

TNHJOURNALPH

RESULT. We herein report a case of a 40-year-old male with mucosa - associated lymphoid tissue. [MALT] lymphoma of the transverse colon, ascending colon and caecum. He presented with severe abdominal pains and a centrally located huge abdominal mass for which a surgical resection was done. Histologically.

Assessment of global and gene-specific DNA methylation in rat liver and kidney in response to non-genotoxic carcinogen exposure

Energy Technology Data Exchange (ETDEWEB)

Ozden, Sibel, E-mail: stopuz@istanbul.edu.tr [Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul (Turkey); Turgut Kara, Neslihan [Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, Istanbul (Turkey); Sezerman, Osman Ugur [Department of Biostatistics and Medical Informatics, Acibadem University, Istanbul (Turkey); Durasi, İlknur Melis [Biological Sciences and Bioengineering, Faculty of Engineering and Natural Sciences, Sabancı University, Istanbul (Turkey); Chen, Tao [Department of Toxicology, School of Public Health, Soochow University, Suzhou (China); Demirel, Goksun; Alpertunga, Buket [Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul (Turkey); Chipman, J. Kevin [School of Biosciences, The University of Birmingham, Birmingham (United Kingdom); Mally, Angela [Department of Toxicology, University of Würzburg, Würzburg (Germany)

2015-12-01

Altered expression of tumor suppressor genes and oncogenes, which is regulated in part at the level of DNA methylation, is an important event involved in non-genotoxic carcinogenesis. This may serve as a marker for early detection of non-genotoxic carcinogens. Therefore, we evaluated the effects of non-genotoxic hepatocarcinogens, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), hexachlorobenzene (HCB), methapyrilene (MPY) and male rat kidney carcinogens, d-limonene, p-dichlorobenzene (DCB), chloroform and ochratoxin A (OTA) on global and CpG island promoter methylation in their respective target tissues in rats. No significant dose-related effects on global DNA hypomethylation were observed in tissues of rats compared to vehicle controls using LC–MS/MS in response to short-term non-genotoxic carcinogen exposure. Initial experiments investigating gene-specific methylation using methylation-specific PCR and bisulfite sequencing, revealed partial methylation of p16 in the liver of rats treated with HCB and TCDD. However, no treatment related effects on the methylation status of Cx32, e-cadherin, VHL, c-myc, Igfbp2, and p15 were observed. We therefore applied genome-wide DNA methylation analysis using methylated DNA immunoprecipitation combined with microarrays to identify alterations in gene-specific methylation. Under the conditions of our study, some genes were differentially methylated in response to MPY and TCDD, whereas d-limonene, DCB and chloroform did not induce any methylation changes. 90-day OTA treatment revealed enrichment of several categories of genes important in protein kinase activity and mTOR cell signaling process which are related to OTA nephrocarcinogenicity. - Highlights: • Studied non-genotoxic carcinogens caused no change on global DNA hypomethylation. • d-Limonene, DCB and chloroform did not show any genome-wide methylation changes. • Some genes were differentially methylated in response to MPY, TCDD and OTA. • Protein kinase activity

Assessment of global and gene-specific DNA methylation in rat liver and kidney in response to non-genotoxic carcinogen exposure

International Nuclear Information System (INIS)

Ozden, Sibel; Turgut Kara, Neslihan; Sezerman, Osman Ugur; Durasi, İlknur Melis; Chen, Tao; Demirel, Goksun; Alpertunga, Buket; Chipman, J. Kevin; Mally, Angela

2015-01-01

Altered expression of tumor suppressor genes and oncogenes, which is regulated in part at the level of DNA methylation, is an important event involved in non-genotoxic carcinogenesis. This may serve as a marker for early detection of non-genotoxic carcinogens. Therefore, we evaluated the effects of non-genotoxic hepatocarcinogens, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), hexachlorobenzene (HCB), methapyrilene (MPY) and male rat kidney carcinogens, d-limonene, p-dichlorobenzene (DCB), chloroform and ochratoxin A (OTA) on global and CpG island promoter methylation in their respective target tissues in rats. No significant dose-related effects on global DNA hypomethylation were observed in tissues of rats compared to vehicle controls using LC–MS/MS in response to short-term non-genotoxic carcinogen exposure. Initial experiments investigating gene-specific methylation using methylation-specific PCR and bisulfite sequencing, revealed partial methylation of p16 in the liver of rats treated with HCB and TCDD. However, no treatment related effects on the methylation status of Cx32, e-cadherin, VHL, c-myc, Igfbp2, and p15 were observed. We therefore applied genome-wide DNA methylation analysis using methylated DNA immunoprecipitation combined with microarrays to identify alterations in gene-specific methylation. Under the conditions of our study, some genes were differentially methylated in response to MPY and TCDD, whereas d-limonene, DCB and chloroform did not induce any methylation changes. 90-day OTA treatment revealed enrichment of several categories of genes important in protein kinase activity and mTOR cell signaling process which are related to OTA nephrocarcinogenicity. - Highlights: • Studied non-genotoxic carcinogens caused no change on global DNA hypomethylation. • d-Limonene, DCB and chloroform did not show any genome-wide methylation changes. • Some genes were differentially methylated in response to MPY, TCDD and OTA. • Protein kinase activity

Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer research

NARCIS (Netherlands)

Tetteh, Paul W.; Kretzschmar, Kai; Begthel, Harry; Van Den Born, Maaike; Korving, Jeroen; Morsink, Folkert; Farin, Henner; Van Es, Johan H.; Offerhaus, G. Johan A; Clevers, Hans

2016-01-01

Current mouse models for colorectal cancer often differ significantly from human colon cancer, being largely restricted to the small intestine. Here, we aim to develop a colon-specific inducible mouse model that can faithfully recapitulate human colon cancer initiation and progression. Carbonic

The application of structure-based assessment to support safety and chemistry diligence to manage genotoxic impurities in active pharmaceutical ingredients during drug development.

Science.gov (United States)

Dobo, Krista L; Greene, Nigel; Cyr, Michelle O; Caron, Stéphane; Ku, Warren W

2006-04-01

Starting materials and intermediates used to synthesize pharmaceuticals are reactive in nature and may be present as impurities in the active pharmaceutical ingredient (API) used for preclinical safety studies and clinical trials. Furthermore, starting materials and intermediates may be known or suspected mutagens and/or carcinogens. Therefore, during drug development due diligence need be applied from two perspectives (1) to understand potential mutagenic and carcinogenic risks associated with compounds used for synthesis and (2) to understand the capability of synthetic processes to control genotoxic impurities in the API. Recently, a task force comprised of experts from pharmaceutical industry proposed guidance, with recommendations for classification, testing, qualification and assessing risk of genotoxic impurities. In our experience the proposed structure-based classification, has differentiated 75% of starting materials and intermediates as mutagenic and non-mutagenic with high concordance (92%) when compared with Ames results. Structure-based assessment has been used to identify genotoxic hazards, and prompted evaluation of fate of genotoxic impurities in API. These two assessments (safety and chemistry) culminate in identification of genotoxic impurities known or suspected to exceed acceptable levels in API, thereby triggering actions needed to assure appropriate control and measurement methods are in place. Hypothetical case studies are presented demonstrating this multi-disciplinary approach.

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.

Absence of genotoxic activity from milk and water boiled in microwave oven in somatic cells from Drosophila melanogaster

International Nuclear Information System (INIS)

Dias, Cristina das Dores.

2003-01-01

This paper reports an experiment for evaluation of the possible genotoxic effects of food prepared in a microwave oven, through the mutation test and somatic recombination, in wings of Drosophila melanogaster. Two crossing have been performed: a standard cross-ST and a high bioactivation cross - HB resulting in marked trans -heterozygote descendents (MH) and balanced heterozygotes (BH). The 72 hours larvas were fed with water and milk boiled both in the microwave oven and in the traditional way. The MH individual wings were analyzed, where the spots can be induced either by mutation or mitotic recombination. The experiment presented negative results related to the genotoxic effects of the water and milk boiled using the microwave oven, in MH descendents of both crossing. Therefore, under these experimental conditions, genotoxic activity were not presented by milk and water boiled in the microwave oven. However, an extensive study using different techniques is necessary to investigate the action of the food prepared in the microwave oven on the genetic material

Genotoxicity of extracts of Japanese traditional herbal medicines (Kampo)

OpenAIRE

Makoto, Katami; Haruo, Kuboniwa; Shunichi, Maemura; Toshihiko, Yanagisawa; New Drug Discovery Laboratory, R & D Division, TSUMURA & Co.; New Drug Discovery Laboratory, R & D Division, TSUMURA & Co.; New Drug Discovery Laboratory, R & D Division, TSUMURA & Co.; New Drug Discovery Laboratory, R & D Division, TSUMURA & Co.

2002-01-01

The possible genotoxicity potential of 128 Japanese traditional herbal medicines (Kampo) was investigated using a bacterial reverse mutation test (the Ames test), an in vivo micronucleus test (MN test) in mouse bone marrow cells and an unscheduled DNA synthesis test (UDS test) in rat hepatocytes. Of 128 Kampo extracts examined, 98 did not induce mutations in bacteria while 30 induced mutations weakly in Salmonella typhimurium TA1537. Extracts of Scutellariae Radix, a common herbal drug, and i...

Evolving colon injury management: a review.

Science.gov (United States)

Greer, Lauren T; Gillern, Suzanne M; Vertrees, Amy E

2013-02-01

The colon is the second most commonly injured intra-abdominal organ in penetrating trauma. Management of traumatic colon injuries has evolved significantly over the past 200 years. Traumatic colon injuries can have a wide spectrum of severity, presentation, and management options. There is strong evidence that most non-destructive colon injuries can be successfully managed with primary repair or primary anastomosis. The management of destructive colon injuries remains controversial with most favoring resection with primary anastomosis and others favor colonic diversion in specific circumstances. The historical management of traumatic colon injuries, common mechanisms of injury, demographics, presentation, assessment, diagnosis, management, and complications of traumatic colon injuries both in civilian and military practice are reviewed. The damage control revolution has added another layer of complexity to management with continued controversy.

Evaluation of genotoxicity and cytotoxicity of water samples from the Sinos River Basin, southern Brazil

Directory of Open Access Journals (Sweden)

E Bianchi

Full Text Available Some water bodies in the Sinos River Basin (SRB have been suffering the effects of pollution by residential, industrial and agroindustrial wastewater. The presence of cytotoxic and genotoxic compounds could compromise the water quality and the balance of these ecosystems. In this context, the research aimed to evaluate the genotoxicity and cytotoxicity of the water at four sites along the SRB (in the cities of Santo Antônio da Patrulha, Parobé, Campo Bom and Esteio, using bioassays in fish and cell culture. Samples of surface water were collected and evaluated in vitro using the Astyanax jacuhiensis fish species (micronucleus test and comet assay and the Vero lineage of cells (comet assay and cytotoxicity tests, neutral red - NR and tetrazolium MTT. The micronucleus test in fish showed no significant differences between the sampling sites, and neither did the comet assay and the MTT and NR tests in Vero cells. The comet assay showed an increase in genetic damage in the fish exposed to water samples collected in the middle and lower sections of the basin (Parobé, Campo Bom and Esteio when compared to the upper section of the basin (Santo Antônio da Patrulha. The results indicate contamination by genotoxic substances starting in the middle section of the SRB.

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

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.

Genotoxic effects of zinc oxide nanoparticles

Science.gov (United States)

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

2015-05-01

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

[Study on the chemical components of edible oil fume in kitchen and its genotoxity on Drosophila].

Science.gov (United States)

Li, S; Wang, Y; Zhang, J; Zhao, X

1999-01-30

To study the chemical components of the condensate of edible oil fume in kitchen and its genotoxicity on Drosophila. Analysis for the chemical components was carried out by gas chromatography and mass spectra (GC/MS) and its genotoxicity was studied by sex linked recessive lethal (SLRL) test in Drosophila. A total of 74 organic compounds were found in samples of condensed oil from the fume in kitchen. It included hydroxylic acids, hydrocarbons, alcohols, esters, aldehydes, ketones, aromatic compounds, and steroids, etc. The total mutagenicity rates in SLRL test induced by the samples at concentrations of 110,320 and 960 mg/L were 0.1732%, 0.4306% and 0.1707% respectively. The sterility rates of the first broods were 2.564%, 2.056% and 2.845% at above 3 concentrations respectively(P < 0.05, as compared with the control). The mutagenicity rate of the second brood at 320 mg/L was 0.530% and that of the third brood at 110 mg/L 0.540%(P < 0.001). Some of the compounds in the condensate of edible oil fume were proved to have high recessive lethal effect and genotoxic effect on the reproductive system of Drosophila.

A comparative genotoxicity study of a supraphysiological dose of triiodothyronine (T₃) in obese rats subjected to either calorie-restricted diet or hyperthyroidism.

Science.gov (United States)

De Sibio, Maria Teresa; Luvizotto, Renata Azevedo Melo; Olimpio, Regiane Marques Castro; Corrêa, Camila Renata; Marino, Juliana; de Oliveira, Miriane; Conde, Sandro José; Ferreira, Ana Lúcia dos Anjos; Padovani, Carlos Roberto; Nogueira, Célia Regina

2013-01-01

This study was designed to determine the genotoxicity of a supraphysiological dose of triiodothyronine (T3) in both obese and calorie-restricted obese animals. Fifty male Wistar rats were randomly assigned to one of the two following groups: control (C; n = 10) and obese (OB; n = 40). The C group received standard food, whereas the OB group was fed a hypercaloric diet for 20 weeks. After this period, half of the OB animals (n = 20) were subjected to a 25%-calorie restriction of standard diet for 8 weeks forming thus a new group (OR), whereas the remaining OB animals were kept on the initial hypercaloric diet. During the following two weeks, 10 OR animals continued on the calorie restriction diet, whereas the remaining 10 rats of this group formed a new group (ORS) given a supraphysiological dose of T3 (25 µg/100 g body weight) along with the calorie restriction diet. Similarly, the remaining OB animals were divided into two groups, one that continued on the hypercaloric diet (OB, n = 10), and one that received the supraphysiological dose of T3 (25 µg/100 g body weight) along with the hypercaloric diet (OS, n = 10) for two weeks. The OB group showed weight gain, increased adiposity, insulin resistance, increased leptin levels and genotoxicity; T3 administration in OS animals led to an increase in genotoxicity and oxidative stress when compared with the OB group. The OR group showed weight loss and normalized levels of adiposity, insulin resistance, serum leptin and genotoxicity, thus having features similar to those of the C group. On the other hand, the ORS group, compared to OR animals, showed higher genotoxicity. Our results indicate that regardless of diet, a supraphysiological dose of T3 causes genotoxicity and potentiates oxidative stress.

Evaluation of the genotoxic and cytotoxic potential of mainstream whole smoke and smoke condensate from a cigarette containing a novel carbon filter.

Science.gov (United States)

Bombick, D W; Bombick, B R; Ayres, P H; Putnam, K; Avalos, J; Borgerding, M F; Doolittle, D J

1997-09-01

A novel carbon filter has been developed which primarily reduces the amount of certain vapor phase constituents of tobacco smoke with greater efficiency than the charcoal filters of cigarettes currently in the market. In vitro indicators of genotoxic and cytotoxic potential were used to compare the cigarette smoke condensate (particulate phase) or whole cigarette smoke (vapor phase and particulate phase) from cigarettes containing the novel carbon filter with smoke condensate or whole smoke from commercial or prototype cigarettes not containing the novel carbon filter. Ames bacterial mutagenicity, sister chromatid exchange (SCE) in Chinese hamster ovary (CHO) cells, and neutral red cytotoxicity assays in CHO cells were utilized to assess the genotoxic and cytotoxic potential of the cigarette smoke condensates. SCE and neutral red cytotoxicity assays were utilized to assess the genotoxic and cytotoxic potential of the whole smoke. As expected, the novel carbon filter did not significantly affect the genotoxic or cytotoxic activity of the smoke condensate, although we did observe that the use of low-nitrogen tobacco reduced the mutagenicity of the condensate in Salmonella typhimurium strain TA98. However, the whole smoke from cigarettes containing the novel carbon filter demonstrated significant reductions in genotoxic and cytotoxic potential compared to cigarettes without the novel carbon filter. The toxicity of the smoke was correlated (r = 0.7662 for cytotoxicity and r = 0.7562 for SCE induction) to the aggregate mass of several vapor phase components (acetone, acetaldehyde, acrolein, acrylonitrile, 1,3-butadiene, ammonia, NOx, HCN, benzene, isoprene, and formaldehyde) in the smoke of the cigarettes utilized in this study. In conclusion, this novel carbon filter, which significantly reduced the amount of carbonyls and other volatiles in mainstream cigarette smoke, resulted in significant reductions in the genotoxic and cytotoxic activity of the smoke as measured

A comparative genotoxicity study of a supraphysiological dose of triiodothyronine (T₃ in obese rats subjected to either calorie-restricted diet or hyperthyroidism.

Directory of Open Access Journals (Sweden)

Maria Teresa De Sibio

Full Text Available This study was designed to determine the genotoxicity of a supraphysiological dose of triiodothyronine (T3 in both obese and calorie-restricted obese animals. Fifty male Wistar rats were randomly assigned to one of the two following groups: control (C; n = 10 and obese (OB; n = 40. The C group received standard food, whereas the OB group was fed a hypercaloric diet for 20 weeks. After this period, half of the OB animals (n = 20 were subjected to a 25%-calorie restriction of standard diet for 8 weeks forming thus a new group (OR, whereas the remaining OB animals were kept on the initial hypercaloric diet. During the following two weeks, 10 OR animals continued on the calorie restriction diet, whereas the remaining 10 rats of this group formed a new group (ORS given a supraphysiological dose of T3 (25 µg/100 g body weight along with the calorie restriction diet. Similarly, the remaining OB animals were divided into two groups, one that continued on the hypercaloric diet (OB, n = 10, and one that received the supraphysiological dose of T3 (25 µg/100 g body weight along with the hypercaloric diet (OS, n = 10 for two weeks. The OB group showed weight gain, increased adiposity, insulin resistance, increased leptin levels and genotoxicity; T3 administration in OS animals led to an increase in genotoxicity and oxidative stress when compared with the OB group. The OR group showed weight loss and normalized levels of adiposity, insulin resistance, serum leptin and genotoxicity, thus having features similar to those of the C group. On the other hand, the ORS group, compared to OR animals, showed higher genotoxicity. Our results indicate that regardless of diet, a supraphysiological dose of T3 causes genotoxicity and potentiates oxidative stress.

Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)

OpenAIRE

Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

2014-01-01

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration tes...

Genotoxicity evaluation of HMG CoA reductase inhibitor rosuvastatin.

Science.gov (United States)

Berber, Ahmet Ali; Celik, Mustafa; Aksoy, Hüseyin

2014-07-01

The genotoxic potential of rosuvastatin as one of the statin drugs was assessed by chromosomal aberrations (CAs), micronucleus (MN) and DNA damage by comet assay in the human peripheral blood lymphocytes. Rosuvastatin was used at concentrations of 0.0625, 0.125, 0.25, 0.5 and 1 µg/mL for these in vitro assays. In all assays, a negative and positive control were also included. CA frequencies were significantly increased in all concentrations at 24 hours and significantly increased in all concentrations except 0.0625 µg/mL at 48 hours, compared to the negative control. Rosuvastatin has a decreased mitotic index (MI) at 0.5- and 1-µg/mL concentrations at 24 hours and at 0.25, 0.5 and 1 µg/mL at 48 hours. A significant increase was observed for induction of MN in all treatments, compared to the negative control. Cytokinesis-block proliferation indices were not affected by treatments with rosuvastatin. In the comet assay, significant increases in comet tail length and tail moment were observed at 0.0625-, 0.5- and 1-µg/mL concentrations. Comet intensity was significantly increased in all concentrations except 0.0625 µg/mL. According to these results, rosuvastatin is cytotoxic and clastogenic/aneugenic in human peripheral lymphocytes. Further studies should be conducted in other test systems to evaluate the full genotoxic potential of rosuvastatin.

Characterization of TCHQ-induced genotoxicity and mutagenesis using the pSP189 shuttle vector in mammalian cells

Energy Technology Data Exchange (ETDEWEB)

Wang Jing, E-mail: avaecn@gmail.com [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Yu Shouyi [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Jiao Shouhai [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Shandong Institute of Endocrine and Metabolic Diseases, Shandong Academy of Medical Sciences, Jinan 250062 (China); Lv Xiaowen [Feed Safety Reference Laboratory of Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081 (China); Ma Min [Laboratory of Environmental Biotechnology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Zhu Benzhan; Du Yuguo [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China)

2012-01-03

Tetrachlorohydroquinone (TCHQ) is a major toxic metabolite of the widely used wood preservative, pentachlorophenol (PCP), and it has also been implicated in PCP genotoxicity. However, the underlying mechanisms of genotoxicity and mutagenesis induced by TCHQ remain unclear. In this study, we examined the genotoxicity of TCHQ by using comet assays to detect DNA breakage and formation of TCHQ-DNA adducts. Then, we further verified the levels of mutagenesis by using the pSP189 shuttle vector in A549 human lung carcinoma cells. We demonstrated that TCHQ causes significant genotoxicity by inducing DNA breakage and forming DNA adducts. Additionally, DNA sequence analysis of the TCHQ-induced mutations revealed that 85.36% were single base substitutions, 9.76% were single base insertions, and 4.88% were large fragment deletions. More than 80% of the base substitutions occurred at G:C base pairs, and the mutations were G:C to C:G, G:C to T:A or G:C to A:T transversions and transitions. The most common types of mutations in A549 cells were G:C to A:T (37.14%) and A:T to C:G transitions (14.29%) and G:C to C:G (34.29%) and G:C to T:A (11.43%) transversions. We identified hotspots at nucleotides 129, 141, and 155 in the supF gene of plasmid pSP189. These mutation hotspots accounted for 63% of all single base substitutions. We conclude that TCHQ induces sequence-specific DNA mutations at high frequencies. Therefore, the safety of using this product would be carefully examined.

Carotenoids and colon cancer.

Science.gov (United States)

Slattery, M L; Benson, J; Curtin, K; Ma, K N; Schaeffer, D; Potter, J D

2000-02-01

Carotenoids have numerous biological properties that may underpin a role for them as chemopreventive agents. However, except for beta-carotene, little is known about how dietary carotenoids are associated with common cancers, including colon cancer. The objective of this study was to evaluate associations between dietary alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, and beta-cryptoxanthin and the risk of colon cancer. Data were collected from 1993 case subjects with first primary incident adenocarcinoma of the colon and from 2410 population-based control subjects. Dietary data were collected from a detailed diet-history questionnaire and nutrient values for dietary carotenoids were obtained from the US Department of Agriculture-Nutrition Coordinating Center carotenoid database (1998 updated version). Lutein was inversely associated with colon cancer in both men and women [odds ratio (OR) for upper quintile of intake relative to lowest quintile of intake: 0.83; 95% CI: 0.66, 1.04; P = 0.04 for linear trend]. The greatest inverse association was observed among subjects in whom colon cancer was diagnosed when they were young (OR: 0.66; 95% CI: 0.48, 0.92; P = 0.02 for linear trend) and among those with tumors located in the proximal segment of the colon (OR: 0.65; 95% CI: 0.51, 0.91; P lettuce, tomatoes, oranges and orange juice, carrots, celery, and greens. These data suggest that incorporating these foods into the diet may help reduce the risk of developing colon cancer.

Colon diversion versus primary colonic repair in gunshot abdomen with penetrating colon injury in Libyan revolution conflict 2011 (a single center experience).

Science.gov (United States)

Mansor, Salah; Bendardaf, Rashed; Bougrara, Muftah; Hagam, Mohamed

2014-09-01

The objective of this study is comparing colon diversion versus primary repair in penetrating colon gunshot injuries. A retrospective study of 63 cases of gunshot abdomen with penetrating colon injury were admitted to Al-jalla Hospital in 2011 in Benghazi, Libya. After surgical intervention, these patients were observed for any postoperative complications. During the study period, 63 eligible patients included, 62 (98.4%) were males and 1 (1.6%) was female. And the mean age was 29.24 years. Eighteen patients had an injury on the right side of the colon, while 16, 6, 11, 6, 2, 3, and 1 patients had an injury on the transverse, left, sigmoid, rectum, right transverse, left transverse, and total colonic injury, respectively. In the first group, 23 patients (36.5%) was treated with colon diversion, (2 with Hartmann's operation, 21 with loop colostomy). In the second group, 40 patients (63.4 %) was treated with primary repair. Eighteen (28.5%) with right hemicolectomy, 5 (7.9%) with transverse colon resection and anastomosis, and 17 (26.9%) with simple repair. We evaluate the rate of postoperative complication and compare the postoperative morbidity between both groups. In our study, there was no significant statistical difference between types of operations and rate of complications (P = 0.18). We could not see any advantage of the diversion over the primary repair. To reduce risk of the psychological trauma, complications of colostomy, unnecessary repeated hospitalization, decrease of economic cost, and complications of stoma revision operation, we should consider that the primary repair of penetrating colon injuries is an acceptable alternative method of treatment over the colostomy.

Oxidative stress and genotoxicity induced by ketorolac on the common carp Cyprinus carpio.

Science.gov (United States)

Galar-Martínez, M; García-Medina, S; Gómez-Olivan, L M; Pérez-Coyotl, I; Mendoza-Monroy, D J; Arrazola-Morgain, R E

2016-09-01

The nonsteroidal anti-inflammatory drug ketorolac is extensively used in the treatment of acute postoperative pain. This pharmaceutical has been found at concentrations of 0.2-60 µg/L in diverse water bodies around the world; however, its effects on aquatic organisms remain unknown. The present study, evaluated the oxidative stress and genotoxicity induced by sublethal concentrations of ketorolac (1 and 60 µg/L) on liver, brain, and blood of the common carp Cyprinus carpio. This toxicant induced oxidative damage (increased lipid peroxidation, hydroperoxide content, and protein carbonyl content) as well as changes in antioxidant status (superoxide dismutase, catalase, and glutathione peroxidase activity) in liver and brain of carp. In blood, ketorolac increased the frequency of micronuclei and is therefore genotoxic for the test species. The effects observed were time and concentration dependent. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1035-1043, 2016. © 2015 Wiley Periodicals, Inc.

Toxicity and genotoxicity of the quaternary ammonium compound benzalkonium chloride (BAC) using Daphnia magna and Ceriodaphnia dubia as model systems

International Nuclear Information System (INIS)

Lavorgna, Margherita; Russo, Chiara; D'Abrosca, Brigida; Parrella, Alfredo; Isidori, Marina

2016-01-01

The toxicity and genotoxicity of the cationic surfactant benzalkonium chloride (BAC) were studied using Daphnia magna and Ceriodaphnia dubia as model systems. Acute and chronic toxicity testing were performed according to the international standard guidelines and the genotoxicity was detected through the comet assay on cells from whole organisms in vivo exposed. Acute effects occurred at concentrations in the order of tens of μg/L in D. magna and hundreds of μg/L in C. dubia. Chronic effects were found at one order of magnitude less than short-term effects maintaining the same difference in sensitivity between D. magna and C. dubia. BAC induced relevant DNA damage, in both cladocerans; the lowest adverse effect levels were 0.4 and 4 ng/L for D. magna and C. dubia, respectively. As these effective concentrations are far lower than BAC occurrence in surface waters (units of μg/L) a concerning environmental risk cannot be excluded. The findings of this study showed that D. magna and C. dubia, could be used as model organisms to detect acute and chronic toxicity as well as genotoxicity at the whole organism level. - Highlights: • Benzalkonium chloride chronic effect in C. dubia was found at dozens of μg/L. • The LOAEC detected by comet assay in D. magna is in the order of hundreds of pg/L. • D. magna and C. dubia are useful model organisms to detect toxicity and genotoxicity. - Benzalkonium chloride showed chronic toxicity and genotoxicity in Daphnia magna and Ceriodaphnia dubia at concentrations of environmental concern. Daphnids are useful model organisms.

Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm).

Science.gov (United States)

Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

2014-06-01

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.

Determination of spectral markers of cytotoxicity and genotoxicity using in vitro Raman microspectroscopy: cellular responses to polyamidoamine dendrimer exposure.

Science.gov (United States)

Efeoglu, Esen; Casey, Alan; Byrne, Hugh J

2017-10-09

Although consumer exposure to nanomaterials is ever increasing, with potential increased applications in areas such as drug and/or gene delivery, contrast agents and diagnosis, the determination of the cyto- and geno-toxic effects of nanomaterials on human health and the environment still remains challenging. Although many techniques have been established and adapted to determine the cytotoxicity and genotoxicity of nano-sized materials, these techniques remain limited by the number of assays required, total cost, and use of labels and they struggle to explain the underlying interaction mechanisms. In this study, Raman microspectroscopy is employed as an in vitro label-free, high content screening technique to observe toxicological changes within the cell in a multi-parametric fashion. The evolution of spectral markers as a function of time and applied dose has been used to elucidate the mechanism of action of polyamidoamine (PAMAM) dendrimers associated with cytotoxicity and their impact on nuclear biochemistry. PAMAM dendrimers are chosen as a model nanomaterial due to their widely studied cytotoxic and genotoxic properties and commercial availability. Point spectra were acquired from the cytoplasm to monitor the cascade of toxic events occurring in the cytoplasm upon nanoparticle exposure, whereas the spectra acquired from the nucleus and the nucleolus were used to explore PAMAM-nuclear material interaction as well as genotoxic responses.

Pectin-based colon-specific drug delivery

OpenAIRE

Shailendra Shukla; Deepak Jain; Kavita Verma; Shiddarth Verma

2011-01-01

Colon-specific drug delivery have a great importance in the delivery of drugs for the treatment of local colonic, as well as systemic diseases like Crohn′s disease, ulcerative colitis, colorectal cancer, amoebiasis, asthma, arthritis and inflammation which can be achieved by targeted delivery of drug to colon. Specific systemic absorption in the colon gave interesting possibilities for the delivery of protein and peptides. It contains relatively less proteolytic enzyme activities in the colon...

Time-Dependent Toxic and Genotoxic Effects of Zinc Oxide Nanoparticles after Long-Term and Repetitive Exposure to Human Mesenchymal Stem Cells

Directory of Open Access Journals (Sweden)

Pascal Ickrath

2017-12-01

Full Text Available Zinc oxide nanoparticles (ZnO-NP are widely spread in consumer products. Data about the toxicological characteristics of ZnO-NP is still under controversial discussion. The human skin is the most important organ concerning ZnO-NP exposure. Intact skin was demonstrated to be a sufficient barrier against NPs; however, defect skin may allow NP contact to proliferating cells. Within these cells, stem cells are the most important toxicological target for NPs. The aim of this study was to evaluate the genotoxic and cytotoxic effects of ZnO-NP at low-dose concentrations after long-term and repetitive exposure to human mesenchymal stem cells (hMSC. Cytotoxic effects of ZnO-NP were measured by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT assay. Furthermore, genotoxicity was evaluated by the comet assay. For long-term observation over 6 weeks, transmission electron microscopy (TEM was applied. The results of the study indicated cytotoxic effects of ZnO-NP beginning at high concentrations of 50 μg/mL and genotoxic effects in hMSC exposed to 1 and 10 μg/mL ZnO-NP. Repetitive exposure enhanced cyto- but not genotoxicity. Intracellular NP accumulation was observed up to 6 weeks. The results suggest cytotoxic and genotoxic potential of ZnO-NP. Even low doses of ZnO-NP may induce toxic effects as a result of repetitive exposure and long-term cellular accumulation. This data should be considered before using ZnO-NP on damaged skin.

Assessment of the genotoxic impact of pesticides on farming communities in the countryside of Santa Catarina State, Brazil

Directory of Open Access Journals (Sweden)

Jaqueli Salvagni

2011-01-01

Full Text Available The aim of this study was to assess the use of pesticides on farms located in the Lambedor River watershed in Guatambu, State of Santa Catarina, as well as to determine, by micronucleus testing, the risk of genotoxic impact. Samples from locally collected Cyprinus carpio, Hypostomus punctatus, Rhamdia quelen and Oreochromis niloticus gave evidence of a mean increase in micronuclei frequency from 6.21 to 13.78 in 1,000 erythrocytes, a clear indication of the genotoxic potenciality of pesticide residues in regional dams, and their significant contribution to local environmental contamination.

APPLICATION OF KATG::LUX GENE CONSTRUCT FOR CYTOTOXICITY AND GENOTOXICITY MONITORING OF METOPROLOL IN ENVIRONMENT

Directory of Open Access Journals (Sweden)

Eliza Hawrylik

2017-06-01

Full Text Available The aim of the study was the evaluation of usefulness of Escherichia coli K-12 RFM 443 katG::lux for cytotoxicity and genotoxicity monitoring of metoprolol in the environment. Metoprolol is one of the most popular cardiac drug which belongs to the group of β – blockers. The drug was applied at concentrations ranging from 10-1 mg/cm3 to 10-5 mg/cm3. Obtained data indicated the influence of metoprolol on lux gene expression and katG promotor activity in E.coli K-12. The results indicato the possibility of using of Escherichia coli K-12 RFM 443 strain with katG::lux gene construct in the monitoring of cytotoxicity and genotoxicity cardiac drug residues in the environment.

Comparative cytotoxicity and genotoxicity of soluble and particulate hexavalent chromium in human and hawksbill sea turtle (Eretmochelys imbricate) skin cells

OpenAIRE

Young, Jamie L.; Wise, Sandra S.; Xie, Hong; Zhu, Cairong; Fukuda, Tomokazu; Wise, John Pierce

2015-01-01

Chromium is both a global marine pollutant and a known human health hazard. In this study, we compare the cytotoxicity and genotoxicity of both soluble and particulate chromate in human and hawksbill sea turtle (Eretmochelys imbricata) skin fibroblasts. Our data show that both soluble and particulate Cr(VI) induce concentration-dependent increases in cytotoxicity, genotoxicity, and intracellular Cr ion concentrations in both human and hawksbill sea turtle fibroblasts. Based on administered co...

Genotoxicity and potential carcinogenicity of cyanobacterial toxins - a review.

Science.gov (United States)

Zegura, Bojana; Straser, Alja; Filipič, Metka

2011-01-01

The occurrence of cyanobacterial blooms has increased significantly in many regions of the world in the last century due to water eutrophication. These blooms are hazardous to humans, animals, and plants due to the production of cyanotoxins, which can be classified in five different groups: hepatotoxins, neurotoxins, cytotoxins, dermatotoxins, and irritant toxins (lipopolysaccharides). There is evidence that certain cyanobacterial toxins are genotoxic and carcinogenic; however, the mechanisms of their potential carcinogenicity are not well understood. The most frequently occurring and widespread cyanotoxins in brackish and freshwater blooms are the cyclic heptapeptides, i.e., microcystins (MCs), and the pentapeptides, i.e., nodularins (NODs). The main mechanism associated with potential carcinogenic activity of MCs and NOD is the inhibition of protein phosphatases, which leads to the hyperphosphorylation of cellular proteins, which is considered to be associated with their tumor-promoting activity. Apart from this, MCs and NOD induce increased formation of reactive oxygen species and, consequently, oxidative DNA damage. There is also evidence that MCs and NOD induce micronuclei, and NOD was shown to have aneugenic activity. Both cyanotoxins interfere with DNA damage repair pathways, which, along with DNA damage, is an important factor involved in the carcinogenicity of these agents. Furthermore, these toxins increase the expression of TNF-α and early-response genes, including proto-oncogenes, genes involved in the response to DNA damage, cell cycle arrest, and apoptosis. Rodent studies indicate that MCs and NOD are tumor promotors, whereas NOD is thought to have also tumor-initiating activity. Another cyanobacterial toxin, cylindrospermopsin (CYN), which has been neglected for a long time, is lately being increasingly found in the freshwater environment. The principal mechanism of its toxicity is the irreversible inhibition of protein synthesis. It is pro-genotoxic

DNA repair and cyclin D1 polymorphisms and styrene-induced genotoxicity and immunotoxicity

Czech Academy of Sciences Publication Activity Database

Kuricová, Miroslava; Naccarati, Alessio; Kumar, R.; Koskinen, M.; Sanyal, S.; Dušinská, M.; Tulinská, J.; Vodičková, Ludmila; Lisková, A.; Jahnová, E.; Fuortes, L.; Haufroid, V.; Hemminki, K.; Vodička, Pavel

2005-01-01

Roč. 207, - (2005), S302-S309 ISSN 0041-008X R&D Projects: GA ČR GA310/03/0437 Institutional research plan: CEZ:AV0Z5039906 Keywords : styrene genotoxicity * immunotoxicity Subject RIV: FM - Hygiene Impact factor: 3.148, year: 2005

Complications of acromegaly: thyroid and colon.

Science.gov (United States)

Tirosh, Amit; Shimon, Ilan

2017-02-01

In acromegaly the long-term exposure to high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels may result in specific complications in different human organs, including the thyroid gland and the colon. We will review here the evidence available regarding the characteristic thyroid and colon complications in acromegaly. This review summarizes the published data observing noncancerous structural abnormalities (thyroid nodules, colonic polyps) and thyroid and colon cancer in patients diagnosed with acromegaly. Thyroid micro-carcinomas are probably over-diagnosed among acromegalic patients. In regard to colon cancer, there is no sufficient data to suggest that colon cancer risk is higher in acromegaly compared to the general population.

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...

Assessment of genotoxic effects of pesticide and vermicompost treated soil with Allium cepa test

Directory of Open Access Journals (Sweden)

Shivika Datta

2018-07-01

Full Text Available Soil forms a huge reservoir of nutrients that sustains life on earth. Anthropogenic and natural impacts have led to degradation of land which declines the overall quality of soil, water or vegetation. The present study involves comparison of genotoxicity of soil procured from two different agricultural sites, pesticide treated soil (PTS and vermicompost treated soil (VTS. The soil was physico-chemically characterized and showed significant differences in terms of cytotoxicity (root length; mitotic index and genotoxicity (chromosomal aberrations in Allium cepa test. The mitotic index of the control after 24 and 48 h was found to be 26.1 ± 1.6 and 26.1 ± 1.3 respectively. Mitotic index was reduced to 10.3 ± 0.9 and 9.7 ± 0.6 in 100% PTS and 24.4 ± 1.7 and 25.4 ± 0.8 in 100% VTS after 24 and 48 h of exposure, respectively. Clastogenic aberrations were found to be highest (54.5% in 100% PTS which was significantly different from VTS extract. The PTS extracts incurred significantly more cytotoxic and genotoxic effects on A. cepa in comparison to VTS. The result indicates that addition of vermicompost in agriculture field acts as soil ameliorator and plays an important role in promotion of cell division and proliferation, hence good for the plant health and crop productivity.

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

International Nuclear Information System (INIS)

Dopp, E.; Hartmann, L.M.; Recklinghausen, U. von; Florea, A.M.; Rabieh, S.; Shokouhi, B.; Hirner, A.V.; Obe, G.; Rettenmeier, A.W.

2007-01-01

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

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....

Evaluation of toxicity and genotoxicity of 2-chlorophenol on bacteria, fish and human cells.

Science.gov (United States)

Vlastos, Dimitris; Antonopoulou, Maria; Konstantinou, Ioannis

2016-05-01

Due to the extensive use of chlorophenols (CPs) in anthropogenic activities, 2-Chlorophenol (2-CP), among other CPs, can enter aquatic ecosystems and can be harmful to a variety of organisms, including bacteria, fish and humans, that are exposed directly and/or indirectly to such contaminated environments. Based on the existing knowledge and in order to move a step forward, the purpose of this study is to investigate the toxic and mainly the genotoxic effects of 2-CP using a combination of bioassays. The tests include the marine bacterium Vibrio fischeri and micronuclei induction in the erythrocytes of Carassius auratus as well as in cultured human lymphocytes. The results obtained reveal that 2-CP is able to induce dose-dependent toxic and genotoxic effects on the selected tested concentrations under the specific experimental conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of the cytotoxic and genotoxic potential of lecithin/chitosan nanoparticles

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Taner, Gökçe; Yeşilöz, Recep; Özkan Vardar, Deniz; Şenyiğit, Taner; Özer, Özgen; Degen, Gisela H.; Başaran, Nurşen

2014-02-01

Nanoparticles-based drug targeting delivery systems have been introduced in the treatment for various diseases because of their effective properties, although there have been conflicting results on the toxicity of nanoparticles. In the present study, the aim was to evaluate the cytotoxicity and the genotoxicity of different concentrations of lecithin/chitosan nanoparticles with and without clobetasol-17-propionate (CP) by neutral red uptake (NRU) cytotoxicity assay and single cell gel electrophoresis (Comet) and cytokinesis-blocked micronucleus assays. The IC50 values of lecithin/chitosan nanoparticles with/without CP were found as 1.9 and 1.8 %, respectively, in the NRU cytotoxicity test. High concentrations of lecithin/chitosan nanoparticles induced DNA damage in human lymphocytes as evaluated by comet assay. The micronucleus frequency was increased by the lecithin/chitosan treatment in a dose-dependent manner. Also at the two highest concentrations, a significant increase in micronucleus formation was observed. Lecithin/chitosan nanoparticles with CP did not increase the frequency of micronucleus and also did not induce additional DNA damage when compared with lecithin/chitosan nanoparticles without CP; therefore, CP itself has not found to be genotoxic at the studied concentration.

A Comparative Genotoxicity Study of a Supraphysiological Dose of Triiodothyronine (T3) in Obese Rats Subjected to Either Calorie-Restricted Diet or Hyperthyroidism

Science.gov (United States)

De Sibio, Maria Teresa; Luvizotto, Renata Azevedo Melo; Olimpio, Regiane Marques Castro; Corrêa, Camila Renata; Marino, Juliana; de Oliveira, Miriane; Conde, Sandro José; Ferreira, Ana Lúcia dos Anjos; Padovani, Carlos Roberto; Nogueira, Célia Regina

2013-01-01

This study was designed to determine the genotoxicity of a supraphysiological dose of triiodothyronine (T3) in both obese and calorie-restricted obese animals. Fifty male Wistar rats were randomly assigned to one of the two following groups: control (C; n = 10) and obese (OB; n = 40). The C group received standard food, whereas the OB group was fed a hypercaloric diet for 20 weeks. After this period, half of the OB animals (n = 20) were subjected to a 25%-calorie restriction of standard diet for 8 weeks forming thus a new group (OR), whereas the remaining OB animals were kept on the initial hypercaloric diet. During the following two weeks, 10 OR animals continued on the calorie restriction diet, whereas the remaining 10 rats of this group formed a new group (ORS) given a supraphysiological dose of T3 (25 µg/100 g body weight) along with the calorie restriction diet. Similarly, the remaining OB animals were divided into two groups, one that continued on the hypercaloric diet (OB, n = 10), and one that received the supraphysiological dose of T3 (25 µg/100 g body weight) along with the hypercaloric diet (OS, n = 10) for two weeks. The OB group showed weight gain, increased adiposity, insulin resistance, increased leptin levels and genotoxicity; T3 administration in OS animals led to an increase in genotoxicity and oxidative stress when compared with the OB group. The OR group showed weight loss and normalized levels of adiposity, insulin resistance, serum leptin and genotoxicity, thus having features similar to those of the C group. On the other hand, the ORS group, compared to OR animals, showed higher genotoxicity. Our results indicate that regardless of diet, a supraphysiological dose of T3 causes genotoxicity and potentiates oxidative stress. PMID:23468891

Chromosomal abnormalities in roots of aquatic plant Elodea canadensis as a tool for testing genotoxicity of bottom sediments.

Science.gov (United States)

Zotina, Tatiana; Medvedeva, Marina; Trofimova, Elena; Alexandrova, Yuliyana; Dementyev, Dmitry; Bolsunovsky, Alexander

2015-12-01

Submersed freshwater macrophytes are considered as relevant indicators for use in bulk bottom sediment contact tests. The purpose of this study was to estimate the validity of endpoints of aquatic plant Elodea canadensis for laboratory genotoxicity testing of natural bottom sediments. The inherent level of chromosome abnormalities (on artificial sediments) in roots of E. canadensis under laboratory conditions was lower than the percentage of abnormal cells in bulk sediments from the Yenisei River. The percentage of abnormal cells in roots of E. canadensis was more sensitive to the presence of genotoxic agents in laboratory contact tests than in the natural population of the plant. The spectra of chromosomal abnormalities that occur in roots of E. canadensis under natural conditions in the Yenisei River and in laboratory contact tests on the bulk bottom sediments from the Yenisei River were similar. Hence, chromosome abnormalities in roots of E. canadensis can be used as a relevant and sensitive genotoxicity endpoint in bottom sediment-contact tests. Copyright © 2015 Elsevier Inc. All rights reserved.

Approaches to the risk assessment of genotoxic carcinogens in food: a critical appraisal.

NARCIS (Netherlands)

O'Brien, J; Renwick, A G; Constable, A; Dybing, Erik; Müller, D J G; Schlatter, J; Slob, Wout; Tueting, W; Benthem, Jan van; Williams, G M; Wolfreys, A

2006-01-01

The present paper examines the particular difficulties presented by low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, and proposes a structured approach for the evaluation of such compounds. While the ALARA approach is

A MASS BALANCE OF SURFACE WATER GENOTOXICITY IN PROVIDENCE RIVER (RHODE ISLAND USA)

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White and Rasmussen (Mutation Res. 410:223-236) used a mass balance approach to demonstrate that over 85% of the total genotoxic loading to the St. Lawrence River at Montreal is non-industrial. To validate the mass balance approach and investigate the sources of genotoxins in sur...

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.

In vitro and in vivo genotoxic effects of somatic cell nuclear transfer cloned cattle meat.

Science.gov (United States)

Lee, Nam-Jin; Yang, Byoung-Chul; Jung, Yu-Ri; Lee, Jung-Won; Im, Gi-Sun; Seong, Hwan-Hoo; Park, Jin-Ki; Kang, Jong-Koo; Hwang, Seongsoo

2011-09-01

Although the nutritional composition and health status after consumption of the meat and milk derived from both conventionally bred (normal) and somatic cell nuclear transferred (cloned) animals and their progeny are not different, little is known about their food safeties like genetic toxicity. This study is performed to examine both in vitro (bacterial mutation and chromosome aberration) and in vivo (micronucleus) genotoxicity studies of cloned cattle meat. The concentrations of both normal and cloned cattle meat extracts (0-10×) were tested to five strains of bacteria (Salmonella typhimurium: TA98, TA100, TA1535, and TA1537; Escherichia coli: WP2uvrA) for bacterial mutation and to Chinese hamster lung (CHL/IU) cells for chromosome aberration, respectively. For micronucleus test, ICR mice were divided into five dietary groups: commercial pellets (control), pellets containing 5% (N-5) and 10% (N-10) normal cattle meat, and pellets containing 5% (C-5) and 10% (C-10) cloned cattle meat. No test substance-related genotoxicity was noted in the five bacterial strains, CHL/IU cells, or mouse bone marrow cells, suggesting that the cloned cattle meat potentially may be safe in terms of mutagenic hazards. Thus, it can be postulated that the cloned cattle meat do not induce any harmful genotoxic effects in vitro and in vivo. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

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Dionatas Ulises de Oliveira Meneguetti

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.

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...

The Consultancy Activity on In Silico Models for Genotoxic Prediction of Pharmaceutical Impurities.

Science.gov (United States)

Pavan, Manuela; Kovarich, Simona; Bassan, Arianna; Broccardo, Lorenza; Yang, Chihae; Fioravanzo, Elena

2016-01-01

The toxicological assessment of DNA-reactive/mutagenic or clastogenic impurities plays an important role in the regulatory process for pharmaceuticals; in this context, in silico structure-based approaches are applied as primary tools for the evaluation of the mutagenic potential of the drug impurities. The general recommendations regarding such use of in silico methods are provided in the recent ICH M7 guideline stating that computational (in silico) toxicology assessment should be performed using two (Q)SAR prediction methodologies complementing each other: a statistical-based method and an expert rule-based method.Based on our consultant experience, we describe here a framework for in silico assessment of mutagenic potential of drug impurities. Two main applications of in silico methods are presented: (1) support and optimization of drug synthesis processes by providing early indication of potential genotoxic impurities and (2) regulatory evaluation of genotoxic potential of impurities in compliance with the ICH M7 guideline. Some critical case studies are also discussed.

Hydropower reservoirs: cytotoxic and genotoxic assessment using the Allium cepa root model.

Science.gov (United States)

Rambo, Cassiano Lazarotto; Zanotelli, Patrícia; Dalegrave, Daniela; De Nez, Dinara; Szczepanik, Jozimar; Carazek, Fábio; Franscescon, Francini; Rosemberg, Denis Broock; Siebel, Anna Maria; Magro, Jacir Dal

2017-03-01

Hydropower offers a reliable source of electricity in several countries, and Brazil supplies its energy needs almost entirely through hydropower plants. Nevertheless, hydropower plants comprise large buildings and water reservoirs and dams, resulting in huge ecological disruptions. Here, we analyzed the impact of four hydropower reservoirs construction in metals and pesticides incidence and the cytotoxic and genotoxic potential of sediment elutriate of rivers from southern Brazil. Our analyses have evidenced the elevated incidence of different metals (lead, iron, cadmium, and chrome) and pesticides (methyl parathion, atrazine, and 2,4-dichlorophenoxyacetic acid). We showed that Allium cepa exposed to sediment elutriates did not change the seed germination rate and mitotic index. However, roots from Allium cepa exposed to reservoirs sediment elutriates showed increased occurrence of chromosomal aberrations and nuclear abnormalities. Therefore, the results obtained in our study indicate that sediment from reservoirs present elevated concentration of metals and pesticides and a significant genotoxic potential. Taken together, our data support that hydropower reservoirs represent an environmental scenario that could impact surrounding wildlife and population.

Genotoxicity test of Maytenus rigida and Aristolochia birostris in the radicular meristem of the onion, Allium cepa

Directory of Open Access Journals (Sweden)

Sandra S. Mendes

2011-09-01

Full Text Available Medicinal plants are an important source of treatment for many ailments, although little is known of the potential genotoxic effects of most species. In the present study, two species from diverse and medicinally important genera - Maytenus rigida Mart., Celastraceae, and Aristolochia birostris Ducht, Aristolochiaceae - were analyzed to identify potentially significant secondary metabolites and the possible effects of their aqueous and alcoholic extracts on cell division in the onion root stem (genotoxicity test. The phytochemical testing revealed the presence of a number of potentially important secondary compounds in both species, including phenols, flavonoids, triterpenoids, steroids, and saponins. In the genotoxicity tests, no chromosomal abnormalities of any kind were observed in either species. In the case of M. rigida, a significant increase in mitotic activity was observed at the highest concentration. No significant tendency was recorded in A. birostris, although a considerable increase in the prophase was observed at all concentrations of the alcoholic extract. The triterpenoid content of both species may be especially important from a medicinal viewpoint, although recent findings on the carcinogenic potential of Aristolochia extracts demands caution in the interpretation of the results, and the need for further research.

Genotoxicity test of Maytenus rigida and Aristolochia birostris in the radicular meristem of the onion, Allium cepa

Directory of Open Access Journals (Sweden)

Sandra S. Mendes

2012-02-01

Full Text Available Medicinal plants are an important source of treatment for many ailments, although little is known of the potential genotoxic effects of most species. In the present study, two species from diverse and medicinally important genera - Maytenus rigida Mart., Celastraceae, and Aristolochia birostris Ducht, Aristolochiaceae - were analyzed to identify potentially significant secondary metabolites and the possible effects of their aqueous and alcoholic extracts on cell division in the onion root stem (genotoxicity test. The phytochemical testing revealed the presence of a number of potentially important secondary compounds in both species, including phenols, flavonoids, triterpenoids, steroids, and saponins. In the genotoxicity tests, no chromosomal abnormalities of any kind were observed in either species. In the case of M. rigida, a significant increase in mitotic activity was observed at the highest concentration. No significant tendency was recorded in A. birostris, although a considerable increase in the prophase was observed at all concentrations of the alcoholic extract. The triterpenoid content of both species may be especially important from a medicinal viewpoint, although recent findings on the carcinogenic potential of Aristolochia extracts demands caution in the interpretation of the results, and the need for further research.

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.

Muscarinic Receptor Signaling in Colon Cancer

International Nuclear Information System (INIS)

Rosenvinge, Erik C. von; Raufman, Jean-Pierre

2011-01-01

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

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.

Evaluation of the genotoxic effects of chronic low-dose ionizing radiation exposure on nuclear medicine workers

Energy Technology Data Exchange (ETDEWEB)

Sahin, Ali [Department of Nuclear Medicine, Faculty of Medicine, Medical School, Ataturk University, Erzurum (Turkey)], E-mail: alibabam2001@yahoo.com; Tatar, Abdulgani; Oztas, Sitki [Department of Genetics, Faculty of Medicine, Ataturk University, 25240 Erzurum (Turkey); Seven, Bedri; Varoglu, Erhan [Department of Nuclear Medicine, Faculty of Medicine, Medical School, Ataturk University, Erzurum (Turkey); Yesilyurt, Ahmet [Department of Genetics, Faculty of Medicine, Ataturk University, 25240 Erzurum (Turkey); Ayan, Arif Kursad [Department of Nuclear Medicine, Faculty of Medicine, Medical School, Ataturk University, Erzurum (Turkey)

2009-07-15

Introduction: Nuclear medicine workers are occupationally exposed to chronic ionizing radiation. It is known that ionizing radiation may have damaging effects on chromosomes. In the present study, we investigated the genotoxic effects of ionizing radiation on nuclear medicine workers. We used two different indicators of genotoxicity methods: sister chromatid exchange (SCE) and micronucleus (MN). Methods: The present research was carried out using 21 nuclear medicine workers (11 females and 10 males) during two periods: during normal working conditions and after a 1-month vacation. The radiation dose varied from 1.20 to 48.56 mSv, which accumulated during the occupational exposure time between two vacations. Peripheral blood samples were taken from each subject for two distinct lymphocyte cultures (SCE and MN) in each period. Results: In nearly all subjects, SCE values increased significantly during radiation exposure compared to the postvacation period (P<.05). Similarly, MN frequencies in most of the subjects increased significantly during radiation exposure compared to the postvacation period (P<.05). Conclusions: This study revealed that both SCE and MN frequencies in most of the subjects were significantly higher during exposure to ionizing radiation than after a 1-month vacation period. However, this genotoxic effect was reversible in most of the subjects.

Evaluation of the genotoxic effects of chronic low-dose ionizing radiation exposure on nuclear medicine workers

International Nuclear Information System (INIS)

Sahin, Ali; Tatar, Abdulgani; Oztas, Sitki; Seven, Bedri; Varoglu, Erhan; Yesilyurt, Ahmet; Ayan, Arif Kursad

2009-01-01

Introduction: Nuclear medicine workers are occupationally exposed to chronic ionizing radiation. It is known that ionizing radiation may have damaging effects on chromosomes. In the present study, we investigated the genotoxic effects of ionizing radiation on nuclear medicine workers. We used two different indicators of genotoxicity methods: sister chromatid exchange (SCE) and micronucleus (MN). Methods: The present research was carried out using 21 nuclear medicine workers (11 females and 10 males) during two periods: during normal working conditions and after a 1-month vacation. The radiation dose varied from 1.20 to 48.56 mSv, which accumulated during the occupational exposure time between two vacations. Peripheral blood samples were taken from each subject for two distinct lymphocyte cultures (SCE and MN) in each period. Results: In nearly all subjects, SCE values increased significantly during radiation exposure compared to the postvacation period (P<.05). Similarly, MN frequencies in most of the subjects increased significantly during radiation exposure compared to the postvacation period (P<.05). Conclusions: This study revealed that both SCE and MN frequencies in most of the subjects were significantly higher during exposure to ionizing radiation than after a 1-month vacation period. However, this genotoxic effect was reversible in most of the subjects.

Diffuse hemangioma of the colon

International Nuclear Information System (INIS)

Reis, J.; Caseiro-Alves, F.; Cruz, L.; Moreira, A.; Rebelo, O.

1995-01-01

We report two cases of diffuse hemangioma of the colon in adolescent patients. One patient had multiple phleboliths at the lower pelvis identified with plain radiographs of the abdomen. Several aspects were seen on double-contrast enema: luminal narrowing, colonic-wall thickening and submucosal colonic masses that changed in appearance with the degree of colonic distension. Angiography was inconclusive in one case. Use of CT and MR provided relevant information regarding the true extent of the disease, but MR was superior in demonstrating unequivocally the vascular nature of the lesions. (orig.)

Importance of neural mechanisms in colonic mucosal and muscular dysfunction in adult rats following neonatal colonic irritation.

Science.gov (United States)

Chaloner, A; Rao, A; Al-Chaer, E D; Greenwood-Van Meerveld, B

2010-02-01

Previous studies have shown that early life trauma induced by maternal separation or colonic irritation leads to hypersensitivity to colorectal distension in adulthood. We tested the hypothesis that repetitive colorectal distension in neonates leads to abnormalities in colonic permeability and smooth muscle function in the adult rat. In neonatal rats, repetitive colorectal distension was performed on days 8, 10, and 12. As adults, stool consistency was graded from 0 (formed stool) to 3 (liquid stool). Colonic tissue was isolated for histology and myeloperoxidase levels. The colonic mucosa was placed in modified Ussing chambers for measurements of permeability and short-circuit current responses to forskolin, electrical field stimulation, and carbachol. Segments of colonic musculature were placed in organ baths and contractile response to potassium chloride, electrical field stimulation, and carbachol were determined. In adult rats that experienced neonatal colonic irritation, no significant changes in colonic histology or myeloperoxidase activity were observed; however, stool consistency scores were increased. Mucosal permeability, measured as an increase in basal conductance, was significantly increased but no changes in short-circuit current responses were observed. In adulthood, rats that underwent colorectal distension as neonates exhibited an elevated smooth muscle contractile response to potassium chloride, but no changes in response to electrical field stimulation or carbachol. In summary, neonatal colonic irritation, shown previously to produce colonic hypersensitivity, leads to significant alterations in colonic mucosal and smooth muscle function characterized by loose stools, increased mucosal permeability, and increased smooth muscle contractility in the absence of colon inflammation in adulthood. Published by Elsevier Ltd.

Genotoxic and cytotoxic effects of different types of dental cement on normal cultured human lymphocytes.

Science.gov (United States)

Bakopoulou, A; Mourelatos, D; Tsiftsoglou, A S; Giassin, N P; Mioglou, E; Garefis, P

2009-01-31

In this study we have investigated the genotoxic and cytotoxic effects of eluates derived from different types of commercially available dental cements, including glass ionomer cements (GICs) (Ketac Cem/3M ESPE and GC Fuji I/GC Corp), resin-modified glass ionomer cements (RM-GICs) (RelyX Luting/3M ESPE and Vitrebond/3M ESPE) and dual-cure resin cements (RCs) (Variolink II/ Ivoclar-Vivadent and Panavia F 2.0/Kuraray) on normal cultured human lymphocytes. Lymphocyte primary cultures obtained from blood samples of three healthy donors were exposed to serial dilutions of eluates derived from specimens of each material tested. Metaphases were induced with phytohaemagglutinin, collected after 72h treatment by use of colchicine and stained according to the fluorescence plus giemsa (FPG) procedure. Preparations were scored for sister chromatid exchange (SCE) and chromosomal aberrations (CAs), while the proliferation rate index (PRI) was also calculated. Our results show that eluates derived from the RM-GICs and RCs caused severe genotoxic effects by significantly increasing the frequencies of SCEs and CAs in cultures of peripheral blood lymphocytes and by decreasing the relevant PRI values in a dose-dependent manner, whereas the two GICs caused only minor cytogenetic effects. Eluates of the two RM-GICs (Vitrebond and RelyX) were also very cytotoxic, as the first serial dilutions of both materials caused a complete mitotic arrest in lymphocyte cultures. Overall, the degree of genotoxicity and cytotoxicity caused by dental cements decreased as follows: Viterbond>Rely X>Panavia F 2.0>Variolink II>Ketac Cem=GC Fuji I. These results indicate that different types of dental cement differ extensively in their genotoxic and cytotoxic potential and their ability to affect chromosomal integrity, cell-cycle progression, DNA replication and repair. Although these results cannot be directly extrapolated to the clinical situation, the potential occurrence of adverse effects caused by the

Piriformospora indica root colonization triggers local and systemic root responses and inhibits secondary colonization of distal roots.

Science.gov (United States)

Pedrotti, Lorenzo; Mueller, Martin J; Waller, Frank

2013-01-01

Piriformosporaindica is a basidiomycete fungus colonizing roots of a wide range of higher plants, including crop plants and the model plant Arabidopsis thaliana. Previous studies have shown that P. indica improves growth, and enhances systemic pathogen resistance in leaves of host plants. To investigate systemic effects within the root system, we established a hydroponic split-root cultivation system for Arabidopsis. Using quantitative real-time PCR, we show that initial P. indica colonization triggers a local, transient response of several defense-related transcripts, of which some were also induced in shoots and in distal, non-colonized roots of the same plant. Systemic effects on distal roots included the inhibition of secondary P. indica colonization. Faster and stronger induction of defense-related transcripts during secondary inoculation revealed that a P. indica pretreatment triggers root-wide priming of defense responses, which could cause the observed reduction of secondary colonization levels. Secondary P. indica colonization also induced defense responses in distant, already colonized parts of the root. Endophytic fungi therefore trigger a spatially specific response in directly colonized and in systemic root tissues of host plants.

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(NO 3 ) 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 G 2 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. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Colon Cancer Detection by ‘Rendezvous Colonoscopy’: Successful Removal of Stuck Colon Capsule by Conventional Colonoscopy

Directory of Open Access Journals (Sweden)

István Rácz

2010-02-01

Full Text Available Although capsule retention is a known complication of small bowel capsule endoscopy, initial studies with colon capsule endoscopy (CCE have not reported any capsule retention or sticking neither in the small bowel nor in the colon. We report a complication of CCE when the stuck colon capsule was passed through the malignant colon stricture and removed by the aid of a flexible colonoscope. During CCE in a 76-year-old iron deficiency anemia patient the real-time viewing system indicated the colon capsule to be stuck in a malignant ascending colon stricture for more than two hours. With the aim to avoid complete capsule retention, immediate colonoscopy was performed. The stuck capsule was caught by a polypectomy snare, passed through the tumor stricture and finally removed from the large bowel. The current case describes the usefulness of the real-time viewing system. Similar situations may occur during the forthcoming spread of CCE and the present case is an example of how to manage the potentially risky stuck colon capsule condition.

A comparison of foamy and lentiviral vector genotoxicity in SCID-repopulating cells shows foamy vectors are less prone to clonal dominance

Directory of Open Access Journals (Sweden)

Elizabeth M Everson

2016-01-01

Full Text Available Hematopoietic stem cell (HSC gene therapy using retroviral vectors has immense potential, but vector-mediated genotoxicity limits use in the clinic. Lentiviral vectors are less genotoxic than gammaretroviral vectors and have become the vector of choice in clinical trials. Foamy retroviral vectors have a promising integration profile and are less prone to read-through transcription than gammaretroviral or lentiviral vectors. Here, we directly compared the safety and efficacy of foamy vectors to lentiviral vectors in human CD34+ repopulating cells in immunodeficient mice. To increase their genotoxic potential, foamy and lentiviral vectors with identical transgene cassettes with a known genotoxic spleen focus forming virus promoter were used. Both vectors resulted in efficient marking in vivo and a total of 825 foamy and 460 lentiviral vector unique integration sites were recovered in repopulating cells 19 weeks after transplantation. Foamy vector proviruses were observed less often near RefSeq gene and proto-oncogene transcription start sites than lentiviral vectors. The foamy vector group were also more polyclonal with fewer dominant clones (two out of six mice than the lentiviral vector group (eight out of eight mice, and only lentiviral vectors had integrants near known proto-oncogenes in dominant clones. Our data further support the relative safety of foamy vectors for HSC gene therapy.

Nonclinical Safety Assessment of Morus alba L. Fruits: Study of 90-D Toxicity in Sprague Dawley Rats and Genotoxicity in Salmonella.

Science.gov (United States)

Chang, Bo Yoon; Kim, Seon Beom; Lee, Mi Kyeong; Park, Hyun; Kim, Sung Yeon

2016-05-01

Morus alba L. is a traditional herb with a long history of consumption, both as an edible fruit and as medicine. However, its safety evaluation has not yet been established. The objective of this study was to evaluate subchronic oral toxicity and genotoxicity of M. alba L. fruits (MFE). The subchronic toxicity after daily oral administration of MFE at 0, 40, 200, and 1000 mg/kg for 90 d was examined in Sprague Dawley (SD) rats. MFE administration did not lead to death, adverse effects, change in food and water consumption, and body weight gain. Significant toxic effects were not found within the parameters of organ weight, biochemical values, and hematological and urine analysis between the control and the MFE group. The genotoxicity of MFE was assayed by Ames test in Salmonella typhimurium strains TA98, TA102, and TA1535. No genotoxicity was found in all the tested strains. Thus in this study, a no-observed-adverse-effect level for MFE in 90 d repeated oral toxicity study in rats was determined to be greater than 1000 mg/kg regardless of gender. The results also suggested that MFE does not have a genotoxicity potential. © 2016 Institute of Food Technologists®

Genotoxicity assessment of membrane concentrates of landfill leachate treated with Fenton reagent and UV-Fenton reagent using human hepatoma cell line.

Science.gov (United States)

Wang, Guifang; Lu, Gang; Yin, Pinghe; Zhao, Ling; Yu, Qiming Jimmy

2016-04-15

Membrane concentrates of landfill leachates contain organic and inorganic contaminants that could be highly toxic and carcinogenic. In this paper, the genotoxicity of membrane concentrates before and after Fenton and UV-Fenton reagent was assessed. The cytotoxicity and genotoxicity was determined by using the methods of methyltetrazolium (MTT), cytokinesis-block micronucleus (CBMN) and comet assay in human hepatoma cells. MTT assay showed a cytotoxicity of 75% after 24h of exposure to the highest tested concentration of untreated concentrates, and no cytotoxocity for UV-Fenton and Fenton treated concentrates. Both CBMN and comet assays showed increased levels of genotoxicity in cells exposed to untreated concentrates, compared to those occurred in cells exposed to UV-Fenton and Fenton reagent treated concentrates. There was no significant difference between negative control and UV-Fenton treated concentrates for micronucleus and comet assay parameters. UV-Fenton and Fenton treatment, especially the former, were effective methods for degradation of bisphenol A and nonylphenol in concentrates. These findings showed UV-Fenton and Fenton reaction were effective methods for treatment of such complex concentrates, UV-Fenton reagent provided toxicological safety of the treated effluent, and the genotoxicity assays were found to be feasible tools for assessment of toxicity risks of complex concentrates. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)

Science.gov (United States)

Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju

2014-01-01

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions. PMID:25071922

Measurement of micronuclei and internal dose in mice demonstrates that 3-monochloropropane-1,2-diol (3-MCPD) has no genotoxic potency in vivo.

Science.gov (United States)

Aasa, Jenny; Törnqvist, Margareta; Abramsson-Zetterberg, Lilianne

2017-11-01

In this study 3-monochloropropane-1,2-diol (3-MCPD), a compound that appears as contaminant in refined cooking oils, has been studied with regard to genotoxicity in vivo (mice) with simultaneous measurement of internal dose using state-of-the-art methodologies. Genotoxicity (chromosomal aberrations) was measured by flow cytometry with dual lasers as the frequency of micronuclei in erythrocytes in peripheral blood from BalbC mice intraperitoneally exposed to 3-MCPD (0, 50, 75, 100, 125 mg/kg). The internal doses of 3-MCPD in the mice were calculated from N-(2,3-dihydroxypropyl)-valine adducts to hemoglobin (Hb), quantified at very low levels by high-resolution mass spectrometry. Convincing evidence for absence of genotoxic potency in correlation to measured internal doses in the mice was demonstrated, despite relatively high administered doses of 3-MCPD. The results are discussed in relation to another food contaminant that is formed as ester in parallel to 3-MCPD esters in oil processing, i.e. glycidol, which has been studied previously by us in a similar experimental setup. Glycidol has been shown to be genotoxic, and in addition to have ca. 1000 times higher rate of adduct formation compared to that observed for 3-MCPD. The conclusion is that at simultaneous exposure to 3-MCPD and glycidol the concern about genotoxicity would be glycidol. Copyright © 2017 Elsevier Ltd. All rights reserved.

Urotensin-II receptor is over-expressed in colon cancer cell lines and in colon carcinoma in humans.

Science.gov (United States)

Federico, Alessandro; Zappavigna, Silvia; Romano, Marco; Grieco, Paolo; Luce, Amalia; Marra, Monica; Gravina, Antonietta Gerarda; Stiuso, Paola; D'Armiento, Francesco Paolo; Vitale, Giovanni; Tuccillo, Concetta; Novellino, Ettore; Loguercio, Carmela; Caraglia, Michele

2014-01-01

Urotensin (U)-II receptor (UTR) has been previously reported to be over-expressed in a number of tumours. Whether UTR-related pathway plays a role in colon carcinogenesis is unknown. We evaluated UTR protein and mRNA expression in human epithelial colon cancer cell lines and in normal colon tissue, adenomatous polyps and colon cancer. U-II protein expression was assessed in cancer cell lines. Moreover, we evaluated the effects of U-II(4-11) (an UTR agonist), antagonists and knockdown of UTR protein expression through a specific shRNA, on proliferation, invasion and motility of human colon cancer cells. Cancer cell lines expressed U-II protein and UTR protein and mRNA. By immunohistochemistry, UTR was expressed in 5-30% of epithelial cells in 45 normal controls, in 30-48% in 21 adenomatous polyps and in 65-90% in 48 colon adenocarcinomas. UTR mRNA expression was increased by threefold in adenomatous polyps and eightfold in colon cancer, compared with normal colon. U-II(4-11) induced a 20-40% increase in cell growth while the blockade of the receptor with specific antagonists caused growth inhibition of 20-40%. Moreover, the knock down of UTR with a shRNA or the inhibition of UTR with the antagonist urantide induced an approximately 50% inhibition of both motility and invasion. UTR appears to be involved in the regulation of colon cancer cell invasion and motility. These data suggest that UTR-related pathway may play a role in colon carcinogenesis and that UTR may function as a target for therapeutic intervention in colon cancer. © 2013 Stichting European Society for Clinical Investigation Journal Foundation.

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

Science.gov (United States)

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

2016-03-01

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

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.

Impact of PAHs on the development of the arbuscular mycorrhizal fungus, G. Intraradices, on the colonization of chicory and carrot grown in vitro

International Nuclear Information System (INIS)

Verdin, A.; Lounes-Hadj Sahraoui, A.; Fontaine, J.; Grandmougin-Ferjani, A.; Durand, R.

2005-01-01

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous and persistent pollutants found in many environments as result of the incomplete combustion of organic matter, and some of them are of great environmental concern due to their highly cytotoxic, genotoxic and carcinogenic properties for mammals. PAHs are thermodynamically stable and recalcitrant to microbial degradation, due to their aromatic nature and low aqueous solubility. Ecologically and economically speaking, plants have tremendous potential for bio-remediation of PAH-contaminated soils. The effect of plant roots on the dissipation of organic pollutants has mainly been attributed to an increase in microbial population and selection of specialized microbial communities in the rhizosphere, and also by improving physical and chemical soil conditions. Arbuscular mycorrhizal (AM) fungi living in symbiosis with plant roots play an essential role in plant nutrition and stress tolerance. AM plants are known to be involved in the biodegradation of pollutants such as PAHs. The role of AM fungi concerns two aspects: the improvement of the establishment and development of plants on polluted soil and the enhancement of PAHs degradation levels. AM colonization of different plant species is negatively affected when the plants are grown in contaminated soils. Nevertheless the AM colonization was shown to enhance plant survival and growth. Objectives of this work was to study the impact of PAHs on the development of G. intraradices and on the colonization of chicory (Cichorium intybus L.) and carrot (Daucus carota L.) roots transformed by Agrobacterium rhizogenes. Monoxenous root cultures have obvious advantages over traditional systems. This technique provides unique visualization of extra-radical fungus development and also allows an important production of extra-radical hyphae, spores and colonized roots free of any other microorganisms. These aspects are important to evaluate direct impact of PAHs on AM fungal

Impact of PAHs on the development of the arbuscular mycorrhizal fungus, G. Intraradices, on the colonization of chicory and carrot grown in vitro

Energy Technology Data Exchange (ETDEWEB)

Verdin, A.; Lounes-Hadj Sahraoui, A.; Fontaine, J.; Grandmougin-Ferjani, A.; Durand, R. [Universite du Littoral-Cote d' Opale, Lab. de Mycologie/Phytopathologie/Environnement, 62 - Calais (France)

2005-07-01

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous and persistent pollutants found in many environments as result of the incomplete combustion of organic matter, and some of them are of great environmental concern due to their highly cytotoxic, genotoxic and carcinogenic properties for mammals. PAHs are thermodynamically stable and recalcitrant to microbial degradation, due to their aromatic nature and low aqueous solubility. Ecologically and economically speaking, plants have tremendous potential for bio-remediation of PAH-contaminated soils. The effect of plant roots on the dissipation of organic pollutants has mainly been attributed to an increase in microbial population and selection of specialized microbial communities in the rhizosphere, and also by improving physical and chemical soil conditions. Arbuscular mycorrhizal (AM) fungi living in symbiosis with plant roots play an essential role in plant nutrition and stress tolerance. AM plants are known to be involved in the biodegradation of pollutants such as PAHs. The role of AM fungi concerns two aspects: the improvement of the establishment and development of plants on polluted soil and the enhancement of PAHs degradation levels. AM colonization of different plant species is negatively affected when the plants are grown in contaminated soils. Nevertheless the AM colonization was shown to enhance plant survival and growth. Objectives of this work was to study the impact of PAHs on the development of G. intraradices and on the colonization of chicory (Cichorium intybus L.) and carrot (Daucus carota L.) roots transformed by Agrobacterium rhizogenes. Monoxenous root cultures have obvious advantages over traditional systems. This technique provides unique visualization of extra-radical fungus development and also allows an important production of extra-radical hyphae, spores and colonized roots free of any other microorganisms. These aspects are important to evaluate direct impact of PAHs on AM fungal

Human wound colonization by Lucilia eximia and Chrysomya rufifacies (Diptera: Calliphoridae): myiasis, perimortem, or postmortem colonization?

Science.gov (United States)

Sanford, Michelle R; Whitworth, Terry L; Phatak, Darshan R

2014-05-01

The infestation of human or animal tissues by fly larvae has been given distinctive terminology depending on the timing and location of colonization. Wounds and orifices colonized by Diptera in a living human or animal are typically referred to as myiasis. When the colonization occurs after death, it is referred to as postmortem colonization and can be used to estimate the minimum postmortem interval. What happens when the human, as in the case presented here, has a necrotic limb while the human remains alive, at least for a short period of time? The case presented here documents perimortem wound colonization by Lucilia eximia (Wiedemann) and Chrysomya rufifacies (Macquart) and the considerations for approximating development temperatures and estimating the time of colonization (TOC). This represents the first record of L. eximia in human myiasis in the United States and the first record of the co-occurrence of L. eximia and C. rufifacies in human myiasis in the United States. The TOC was estimated using both ambient and body temperature. Insect colonization before death complicates the estimation of TOC and minimum postmortem interval and illustrates the problem of temperature approximation in forensic entomology casework.

Genotoxicity of corrosion eluates obtained from orthodontic brackets in vitro.

Science.gov (United States)

Angelieri, Fernanda; Marcondes, Joao Paulo C; de Almeida, Danielle Cristina; Salvadori, Daisy M F; Ribeiro, Daniel A

2011-04-01

The purpose of this study was to evaluate whether corrosion eluates obtained from commercially available orthodontic brackets are able to induce genetic damage in vitro. Genotoxicity was assessed by the single cell gel (comet) assay using Chinese hamster ovary (CHO) cells. The following orthodontic metallic brackets were used: Morelli (Sorocaba, Brazil); Abzil (São José do Rio Preto, Brazil); Dentaurum (Pforzheim, Germany); and 3M Unitek (Puchheim, Germany). Each dental bracket was submitted to a corrosion process in a solution containing equal amounts of acetic acid and sodium chloride at 0.1 M concentration for 1, 3, 7, 14, 21, 35, and 70 days. CHO cells were exposed to eluates for 30 minutes at 37°C. The negative control was treated with the same solution used for corrosion process for 30 minutes at 37°C. Independent positive control was performed with methyl methanesulfonate (MMS) (Sigma Aldrich, St. Louis, Mo) at 1 ug/mL for 1 hour. None of the eluates was found to exhibit genotoxicity, regardless of the different commercial brands of orthodontic appliance used. In summary, our results indicate corrosion eluates obtained from orthodontic brackets do not induce genetic damage as assessed by single cell gel (comet) assay. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Altered expression of long non-coding RNAs during genotoxic stress-induced cell death in human glioma cells.

Science.gov (United States)

Liu, Qian; Sun, Shanquan; Yu, Wei; Jiang, Jin; Zhuo, Fei; Qiu, Guoping; Xu, Shiye; Jiang, Xuli

2015-04-01

Long non-coding RNAs (lncRNAs), a recently discovered class of non-coding genes, are transcribed throughout the genome. Emerging evidence suggests that lncRNAs may be involved in modulating various aspects of tumor biology, including regulating gene activity in response to external stimuli or DNA damage. No data are available regarding the expression of lncRNAs during genotoxic stress-induced apoptosis and/or necrosis in human glioma cells. In this study, we detected a change in the expression of specific candidate lncRNAs (neat1, GAS5, TUG1, BC200, Malat1, MEG3, MIR155HG, PAR5, and ST7OT1) during DNA damage-induced apoptosis in human glioma cell lines (U251 and U87) using doxorubicin (DOX) and resveratrol (RES). We also detected the expression pattern of these lncRNAs in human glioma cell lines under necrosis induced using an increased dose of DOX. Our results reveal that the lncRNA expression patterns are distinct between genotoxic stress-induced apoptosis and necrosis in human glioma cells. The sets of lncRNA expressed during genotoxic stress-induced apoptosis were DNA-damaging agent-specific. Generally, MEG3 and ST7OT1 are up-regulated in both cell lines under apoptosis induced using both agents. The induction of GAS5 is only clearly detected during DOX-induced apoptosis, whereas the up-regulation of neat1 and MIR155HG is only found during RES-induced apoptosis in both cell lines. However, TUG1, BC200 and MIR155HG are down regulated when necrosis is induced using a high dose of DOX in both cell lines. In conclusion, our findings suggest that the distinct regulation of lncRNAs may possibly involve in the process of cellular defense against genotoxic agents.

Investigations on genotoxic effects of groundwater from the Mitterndorfer Senke and from the vicinity of Wiener Neustadt.

Science.gov (United States)

Knasmüller, S; Helma, C; Eckl, P M; Gottmann, E; Steinkellner, H; Kassie, F; Haider, T; Parzefall, W; Schulte-Hermann, R

1998-12-11

This report describes the first study on genotoxic effects of Austrian ground- and drinking waters. Samples from the Mitterndorfer Senke (MS) and the vicinity of Wiener Neustadt were tested over a three years period. The MS is the largest aquifer in Austria. Due to deposition of industrial and community wastes, chemicals have polluted the groundwater in this area. Aim of the present study was to elucidate if consumption of these waters might pose a carcinogenic risk to humans. 43 Water samples were tested in a test battery which consisted of bacterial gene mutation assays (Salmonella strains TA100 and TA98), micronucleus (MN) assays with cultures of primary rat hepatocytes and plant bioassays (MN tests with Tradescantia and Vicia faba). For the bacterial assays, the water samples were extracted with XAD resins. In total, 27.9% of the samples caused positive effects; 8 samples were active in Salmonella microsome assays, Strain TA100 was particularly sensitive upon addition of metabolic activation mix (6 positive samples). Four samples were positive exclusively in MN assays with cultures of primary rat hepatocytes; one sample gave positive results in all three bioassays. Finished waters from waterworks were consistently devoid of mutagenic activity under all experimental conditions. Overall, only a small fraction of the groundwaters caused mutagenic effects and in all cases the activities were moderate. Comparison of the results of the present study with data obtained in other investigations under similar experimental conditions shows that the genotoxicity of groundwaters of the MS area are lower than the effects caused by ground- and drinking waters from other countries. The fact that no genotoxic activity was detected in any of the finished drinking waters can be taken as an indication that consumption of these waters does not pose a health hazard arising from contamination with genotoxic carcinogens to humans.

Imaging of total colonic Hirschsprung disease

International Nuclear Information System (INIS)

Stranzinger, Enno; DiPietro, Michael A.; Strouse, Peter J.; Teitelbaum, Daniel H.

2008-01-01

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.)

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).

Colon and rectal cancer

International Nuclear Information System (INIS)

Saldombide, L.; Cordoba, A.

2010-01-01

This study is about the diagnosis, therapy and monitoring of colon cancer. The techniques used are the endoscopy with biopsy in the pre and post operative colon surgery, abdominal ultrasound, chest X-ray studies of hemogram as well as liver and renal function

Necrotizing colitis associated with carcinoma of the colon

International Nuclear Information System (INIS)

Woo, Seong Ku; Lim, Jae Hoon; Kim, Soon Yong; Ahn, Chi Yul

1982-01-01

Necrotizing colitis associated with carcinoma of the colon, known also as obstructive colitis, is a disorder characterized by anulceration and inflammation of the colon proximal to an obstructive lesion, especially carcinoma of the rectosigmoid colon, and in rare instance, leads to acute gangrene of the colon. The authors analyzed radiologic findings in four cases of necrotizing colitis associated with carcinoma of the colon. Barium enema disclosed mucosal edema, nodular filling defects, irregularity of the colonic contour and typical thumbprinting appearance of involved colon proximal to an obstructing carcinoma of the colon. The mechanism of necrotizing colitis was briefly reviewed

Genotoxic effects of water pollution on two fish species living in Karasu River, Erzurum, Turkey.

Science.gov (United States)

Yazıcı, Zehra; Sişman, Turgay

2014-11-01

Karasu River, which is the only river in the Erzurum plain, is the source of the Euphrates River (Eastern Anatolia of Turkey). The river is in a serious environmental situation as a result of pollution by agricultural and industrial sewage and domestic discharges. The present study aims to evaluate genotoxic effects of toxic metals in chub, Leuciscus cephalus, and transcaucasian barb, Capoeta capoeta, collected from contaminated site of the Karasu River, in comparison with fish from an unpolluted reference site. Heavy metal concentrations in surface water of the river were determined. The condition factor (CF) was taken as a general biomarker of the health of the fish, and genotoxicity assays such as micronucleus (MN) and other nuclear abnormalities (NA) were carried out on the fish species studied. MN and NA such as kidney-shaped nucleus, notched nucleus, binucleated, lobed nucleus, and blebbed nucleus were assessed in peripheral blood erythrocytes, gill epithelial cells, and liver cells of the fish. A significant decrease in CF values associated with a significant elevation in MN and NA frequencies was observed in fish collected from the polluted sites compared with those from the reference site. Results of the current study show the significance of integrating a set of biomarkers to identify the effects of anthropogenic pollution. High concentrations of heavy metals have a potential genotoxic effects, and the toxicity is possibly related to industrial, agricultural, and domestic activities.

Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

DEFF Research Database (Denmark)

Gallina, Irene; Colding, Camilla Skettrup; Henriksen, Peter

2015-01-01

DNA replication stress is a source of genomic instability. Here we identify changed mutation rate 1 (Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that Cmr1-together with Mrc1/Claspin, Pph3, the chaperonin containing TCP1 (CCT) and 25...... other proteins-define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression...... propose that Cmr1/WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins....

Decrease of 5-Hydroxymethylcytosine in Rat Liver with Subchronic Exposure to Genotoxic Carcinogens Riddelliine and Aristolochic Acid

Science.gov (United States)

Lian, Christine Guo; Xu, Shuyun; Guo, Weimin; Yan, Jian; Frank, Maximilian Y M; Liu, Robert; Liu, Cynthia; Chen, Ying; Murphy, George F.; Chen, Tao

2018-01-01

The level of 5-hydroxymethylcytosine (5-hmC) converted by ten-eleven translocation (TET) family is decreased in cancers. However, whether 5-hmC level is perturbed in early stages of carcinogenesis caused by genotoxic carcinogens is not defined. 5-hmC levels and TET2 expression were measured in liver of rats treated with genotoxic carcinogens, riddelliine, or aristolochic acid. Levels of 5-hmC and TET2 expression decreased in the liver of the carcinogens-treated rats. Loss of 5-hmC correlates well with documented induction of genetic mutations by the carcinogens, suggesting that TET2-mediated 5-hydroxymethylation plays an epigenetic role in early state of carcinogenesis. PMID:25154389

Evalution of the genotoxic effects of tiamulin S-in vivo

OpenAIRE

Marković Biljana; Stanimirović Zoran Ž.; Đelić Ninoslav J.

2004-01-01

In this work the genotoxic effect of the antibiotic preparation Tiamulin S was investigated. The experiments were done in vivo using cytogenetic analysis on BALB/c mouse bone marrow cells. The occurrence of chromosomal alterations was monitored in bone marrow and germ cells. The clastogenic effect of Tiamulin S was monitored at three doses (0.01 ml/kg, 0.2 ml/kg and 0.4 ml/kg) through eight experimental cycles. The results obtained showed that Tiamulin S induces kariotype changes including bo...

Do Dental X-Rays Induce Genotoxicity and Cytotoxicity in Oral Mucosa Cells? A Critical Review.

Science.gov (United States)

Angelieri, Fernanda; Yujra, Veronica Quispe; Oshima, Celina Tizuko Fujiyama; Ribeiro, Daniel Araki

2017-10-01

Dental X-rays are widely used in clinical practice, since the technique is an important approach for diagnosing diseases in dental and periodontal tissues. However, it is widely known that radiation is capable of causing damage to cellular systems, such as genotoxicity or cytotoxicity. Thus, the aim of this review was to present a critical analysis regarding the studies published on genotoxicity and cytotoxicity induced by dental X-rays in oral mucosa cells. Such studies have revealed that some oral cell types are more sensitive than others following exposure to dental X-rays. Certainly, this review will contribute to a better understanding of this matter as well as to highlighting perspectives for further studies. Ultimately, such data will promote better safety for both patients and dental professionals. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Evaluation of the Genotoxic and Antigenotoxic Effects of Andiroba (Carapa guianensis Aublet Oil and Nanoemulsion on Swiss Mice

Directory of Open Access Journals (Sweden)

Karina Motta Melo

2018-01-01

Full Text Available The Carapa guianensis (andiroba oil is commonly used by the Amazon population for medicinal purposes. The objective of this study was to determine the genotoxic and antigenotoxic potential of the andiroba oil (AO and nanoemulsion (AN using Swiss mice. Therefore, we used the comet assay and micronucleus test. The AO predominant compounds were oleic (39.13%, palmitic (33.22%, and linoleic (16.86% acids. AN composition obeyed the surfactant/oil ratio of 0.69, and the Tween 80/Span 80 ratio was held at 0.9. Our results showed no cytotoxicity or genotoxicity in the mice treated with AO and AN alone. However, there was a significant reduction in the polychromatic erythrocytes (PCEs numbers in all groups treated with doxorubicin (DOX, including those pretreated with AO and AN. Thus, the samples tested did not protect against DOX. On the other hand, our results showed a large increase in micronucleus (MN formation when the mice were treated with DOX alone; these numbers were reduced when the animals were pretreated with AO and AN. The results indicate a protective effect of andiroba on MN formation and show no evidence of genotoxicity in mice.

The Usefulness of Intraoperative Colonic Irrigation and Primary Anastomosis in Patients Requiring a Left Colon Resection.

Science.gov (United States)

Hong, Youngki; Nam, Soomin; Kang, Jung Gu

2017-06-01

The aim of this study is to assess the short-term outcome of intraoperative colonic irrigation and primary anastomosis and to suggest the usefulness of the procedure when a preoperative mechanical bowel preparation is inappropriate. This retrospective study included 38 consecutive patients (19 male patients) who underwent intraoperative colonic irrigation and primary anastomosis for left colon disease between January 2010 and December 2016. The medical records of the patients were reviewed to evaluate the patients' characteristics, operative data, and postoperative short-term outcomes. Twenty-nine patients had colorectal cancer, 7 patients had perforated diverticulitis, and the remaining 2 patients included 1 with sigmoid volvulus and 1 with a perforated colon due to focal colonic ischemia. A diverting loop ileostomy was created in 4 patients who underwent a low anterior resection. Complications occurred in 15 patients (39.5%), and the majority was superficial surgical site infections (18.4%). Anastomotic leakage occurred in one patient (2.6%) who underwent an anterior resection due sigmoid colon cancer with obstruction. No significant difference in overall postoperative complications and superficial surgical site infections between patients with obstruction and those with peritonitis were noted. No mortality occurred during the first 30 postoperative days. The median hospital stay after surgery was 15 days (range, 8-39 days). Intraoperative colonic irrigation and primary anastomosis seem safe and feasible in selected patients. This procedure may reduce the burden of colostomy in patients requiring a left colon resection with an inappropriate preoperative mechanical bowel preparation.

Micronuclei as biomarkers of genotoxicity of gamma radiation in aquatic environments

Energy Technology Data Exchange (ETDEWEB)

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

2011-07-01

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

The use of plants containing genotoxic carcinogens as foods and medicine.

Science.gov (United States)

Prinsloo, Gerhard; Nogemane, Noluyolo; Street, Renee

2018-04-05

In many developing countries, populations rely on traditional medicine for primary health care, which have infiltrated commercial markets globally as natural remedies are generally regarded as safe. Traditional and natural remedies are adapted and expanded in commercial products and product ranges to provide alternatives for various diseases and illnesses. These products resemble very little of the traditional use and application and adverse effects are observed in several cases. Some of the herbs and botanical formulations therefore, are not as safe as are commonly contemplated. This paper discusses some plants that are used as food or medicine. These plants are known to contain chemical components that have been identified as genotoxic carcinogens. Often contradictory results are obtained with beneficial and adverse effects reported. The concentration, biotransformation and metabolism of these compounds, as well as the matrix effect, affect the outcome of these results, therefore not providing a clear picture of the risk associated with the use and consumption of these plants. This paper focuses on plants that are accepted as healthy, however contain compounds that are genotoxic and carcinogenic. We further highlight the risks in use of these plants where thorough studies have been conducted in various food and plant products. Copyright © 2018 Elsevier Ltd. All rights reserved.

Micronuclei as biomarkers of genotoxicity of gamma radiation in aquatic environments

International Nuclear Information System (INIS)

Silva, Luanna R.S.; Silva, Edvane B.; Melo, Ana M.M.A.; Silva, Ronaldo C. da; Amancio, Francisco F.

2011-01-01

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

Transformation of cefazolin during chlorination process: Products, mechanism and genotoxicity assessment

Energy Technology Data Exchange (ETDEWEB)

Li, Liping, E-mail: lisaleercees807@yahoo.cn; Wei, Dongbin, E-mail: weidb@rcees.ac.cn; Wei, Guohua, E-mail: wgh@rcees.ac.cn; Du, Yuguo, E-mail: duyuguo@rcees.ac.cn

2013-11-15

Highlights: • Base-catalyzed electrophilic substitution occurred in cefazolin chlorination. • Oxidation of thioether in cefazolin was found in chlorination process. • The pH conditions impacted on the occurrence of reaction types. • Genotoxicity had an elevation after chlorination of cefazolin. • Reaction pathways of cefazolin chlorination were replayed in surface water matrix. -- Abstract: Large quantities of cephalosporins have entered into aquatic environment in recent years, posing potential adverse effect to human health and ecological safety. In this study, cefazolin, one of widely used cephalosporins, was targeted to explore its transformation behaviors in chlorination disinfection process. With the help of ultra high performance liquid chromatography and high resolution mass spectroscopy, one chlorinated product and four oxidation products were detected in cefazolin chlorination system. The corresponding transformation pathways of cefazolin were proposed. Two kinds of reactions occurred in chlorination system, one was oxidation of thioether-sulfur to sulfoxide and di-sulfoxide, and the other was base-catalyzed electrophilic substitution of alpha-H of amide by chlorine atom. The pH value determined the occurrence of reaction types, and increasing chlorine dose promoted transformation of cefazolin. More importantly, genotoxicity in SOS/umu assay had an elevation after chlorination, which might be attributed to the formation of chlorinated product and sulfoxide during chlorination process.

Transformation of cefazolin during chlorination process: Products, mechanism and genotoxicity assessment

International Nuclear Information System (INIS)

Li, Liping; Wei, Dongbin; Wei, Guohua; Du, Yuguo

2013-01-01

Highlights: • Base-catalyzed electrophilic substitution occurred in cefazolin chlorination. • Oxidation of thioether in cefazolin was found in chlorination process. • The pH conditions impacted on the occurrence of reaction types. • Genotoxicity had an elevation after chlorination of cefazolin. • Reaction pathways of cefazolin chlorination were replayed in surface water matrix. -- Abstract: Large quantities of cephalosporins have entered into aquatic environment in recent years, posing potential adverse effect to human health and ecological safety. In this study, cefazolin, one of widely used cephalosporins, was targeted to explore its transformation behaviors in chlorination disinfection process. With the help of ultra high performance liquid chromatography and high resolution mass spectroscopy, one chlorinated product and four oxidation products were detected in cefazolin chlorination system. The corresponding transformation pathways of cefazolin were proposed. Two kinds of reactions occurred in chlorination system, one was oxidation of thioether-sulfur to sulfoxide and di-sulfoxide, and the other was base-catalyzed electrophilic substitution of alpha-H of amide by chlorine atom. The pH value determined the occurrence of reaction types, and increasing chlorine dose promoted transformation of cefazolin. More importantly, genotoxicity in SOS/umu assay had an elevation after chlorination, which might be attributed to the formation of chlorinated product and sulfoxide during chlorination process

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

Science.gov (United States)

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

2016-01-01

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

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

Science.gov (United States)

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

2016-05-01

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

Physicochemical properties, in vitro cytotoxic and genotoxic effects of PM1.0 and PM2.5 from Shanghai, China.

Science.gov (United States)

Zou, Yajuan; Wu, Yizhao; Wang, Yali; Li, Yinsheng; Jin, Chengyu

2017-08-01

Exposure to ambient particulate matter (PM) links with a variety of respiratory diseases. However, compared with coarse particles (PM 10 ) and fine particles (PM 2.5 ), submicrometer particles (PM 1.0 ) may be a more important indicator of human health risks. In this study, the cytotoxic and genotoxic effects of PM 1.0 samples from Shanghai were examined using A549 cells, and compared with the effects of PM 2.5 , to better understand the health effects of PM 1.0 in this area. The PM 1.0 and PM 2.5 samples were characterized for morphology, water-soluble inorganic ions, organic and elemental carbon, and metal elements. The cytotoxicity of PMs was measured using cell viability and cell membrane damage assays. The genotoxic effects of PMs were determined using the comet assay, and DNA damage was quantified using olive tail moment (OTM) values. The physicochemical characterization indicated that PM 1.0 was enriched in carbonaceous elements and hazardous metals (Al, Zn, Pb, Mn, Cu, and V), whereas PM 2.5 was more abundant in large, irregular mineral particles. The biological results revealed that both PM 1.0 and PM 2.5 could induce significant cytotoxicity and genotoxicity in A549 cells, and that exposure to PM 1.0 caused more extensive toxic effects than exposure to PM 2.5 . The greater cytotoxic effects of PM 1.0 can be attributed to the combined effects of size and chemical composition, whereas the genotoxic effects of PM 1.0 may be mainly associated with chemical species.

Acute pseudo-obstruction of the colon

International Nuclear Information System (INIS)

Beese, M.; Heller, M.

1988-01-01

The radiological correlate to the pseudo-obstruction of the colon is not specific, but it does supply a pointer to the disease of it shows dilation of the caecum, colon ascendens and colon transversum with air-pockets and reflected imaging as well as a usually not dilated colon descendens with remarkably little air. To make the diagnosis quite sure we must exclude intestinal obstruction by using X-ray contrast media or by coloscopy. (orig./GDG) [de

Safety evaluation of pectin-derived acidic oligosaccharides (pAOS): genotoxicity and sub-chronic studies.

NARCIS (Netherlands)

Garthoff, J.A.; Heemskerk, S.; Hempenius, R.A.; Lina, B.A.; Krul, C.A.; Koeman, J.H.; Speijers, G.J.

2010-01-01

Pectin-derived acidic oligosaccharides (pAOS) are non-digestible carbohydrates to be used in infant formulae and medical nutrition. To support its safety, the genotoxic potential of pAOS was evaluated. pAOS was not mutagenic in the Ames test. Positive results were obtained in the chromosome

Safety evaluation of pectin-derived acidic oligosaccharides (pAOS): Genotoxicity and sub-chronic studies

NARCIS (Netherlands)

Garthoff, J.A.; Heemskerk, S.; Hempenius, R.A.; Lina, B.A.R.; Krul, C.A.M.; Koeman, J.H.; Speijers, G.J.A.

2010-01-01

Pectin-derived acidic oligosaccharides (pAOS) are non-digestible carbohydrates to be used in infant formulae and medical nutrition. To support its safety, the genotoxic potential of pAOS was evaluated. pAOS was not mutagenic in the Ames test. Positive results were obtained in the chromosome

Colonic motility and enema spreading

International Nuclear Information System (INIS)

Hardy, J.G.; Wood, E.; Clark, A.G.; Reynolds, J.R.; Queen's Medical Centre, Nottingham

1986-01-01

Radiolabelled enema solution was administered to eight healthy subjects, both in fasted and fed states. Enema spreading was monitored over a 4-h period using gamma scintigraphy and colonic motility was recorded simultaneously using a pressure sensitive radiotelemetry capsule. The rate and extent of enema dispersion were unaffected by eating. Spreading could be correlated with colonic motility and was inhibited by aboral propulsion of the colonic contents. (orig.)

Primary closure in colon trauma.

Science.gov (United States)

Salinas-Aragón, Luis Enrique; Guevara-Torres, Lorenzo; Vaca-Pérez, Enrique; Belmares-Taboada, Jaime Arístides; Ortiz-Castillo, Fátima de Guadalupe; Sánchez-Aguilar, Martín

2009-01-01

Primary repair of colon injuries is an accepted therapeutic option; however, controversy persists regarding its safety. Our objective was to report the evolution and presence of complications in patients with colon injury who underwent primary closure and to determine if the time interval (>6 h), degree of injury, contamination, anatomic site injured, PATI (Penetrating Abdominal Trauma Index) >25, and the presence of other injuries in colon trauma are associated with increased morbidity and mortality. This was a prospective, observational, longitudinal and descriptive study conducted at the Central Hospital "Dr. Ignacio Morones Prieto," San Luis Potosí, Mexico, from January 1, 2003 to December 31, 2007. We included patients with abdominal trauma with colon injury subjected to surgical treatment. chi(2) was used for basic statistical analysis. There were 481 patients with abdominal trauma who underwent surgery; 77(16.1%) had colon injury. Ninety percent (n = 69) were treated in the first 6 h; 91% (n = 70) were due to penetrating injuries, and gunshot wound accounted for 48% (n = 37). Transverse colon was the most frequently injured (38%) (n = 29). Grade I and II injuries accounted for 75.3% (n = 58). Procedures included primary repair (76.66 %) (n = 46); resection with anastomosis (8.3%) (n = 5); and colostomy (15%) (n = 9). Associated injuries were present in 76.6% (n = 59). There was some degree of contamination in 85.7% (n = 66); 82.8% (58) had PATI colon injury. Primary repair is a safe procedure for treatment of colon injuries. Patients with primary repair had lower morbidity (p <0.009). Surgery during the first 6 h (p <0.006) and in hemodynamically stable patients (p <0.014) had a lower risk of complications.

Assessment of genotoxicity associated with hydroxyurea therapy in children with sickle cell anemia

Science.gov (United States)

Flanagan, Jonathan M.; Howard, Thad A.; Mortier, Nicole; Avlasevich, Svetlana L.; Smeltzer, Matthew P.; Wu, Song; Dertinger, Stephen D.; Ware, Russell E.

2018-01-01

Hydroxyurea induces fetal hemoglobin, improves laboratory parameters, and ameliorates clinical complications of sickle cell anemia (SCA), but its long-term efficacy and safety in this patient population remain incompletely defined. Although generally considered non-DNA reactive, an important safety concern is that hydroxyurea may indirectly cause genotoxic damage. To better address this safety issue of hydroxyurea in patients with SCA, we measured the production of micronuclei (MN) in red blood cells (RBC) as a marker of genotoxicity. Blood samples were collected from children with SCA enrolled in the Hydroxyurea Study of Long-term Effects (ClinicalTrials.gov NCT00305175). Flow cytometry quantified circulating MN-containing erythrocyte sub-populations before and during hydroxyurea exposure. The frequency of micronucleated reticulocytes (MN-CD71+) and micronucleated mature erythrocytes (MN-RBC) were then tested for associations with laboratory and clinical data. In cross-sectional analysis of 293 blood samples from 105 children with SCA and a median of 2 years of hydroxyurea therapy, exposure to hydroxyurea was associated with significantly increased frequencies of MN-CD71+ and MN-RBC compared to baseline. The increases were evident by 3 months of therapy, and did not escalate further with up to 12 years of continuous drug exposure. In prospective longitudinal analysis, substantial inter-individual variation in the effect of hydroxyurea on %MN-CD71+ was observed that was associated with the expected laboratory effects of hydroxyurea. In conclusion, clinically relevant exposure to hydroxyurea is associated with increased MN production consistent with erythroblast genotoxicity but with substantial inter-patient variability. Associations between increased %MN-CD71+ and laboratory benefits suggest that hydroxyurea effects on MN production may be related to individual patient sensitivity to hydroxyurea within the bone marrow. PMID:20230905

Genotoxicity profile of erinacine A-enriched Hericium erinaceus mycelium.

Science.gov (United States)

Li, I-Chen; Chen, Yen-Lien; Chen, Wan-Ping; Lee, Li-Ya; Tsai, Yueh-Ting; Chen, Chin-Chu; Chen, Chin-Shuh

2014-01-01

Hericium erinaceus ( H. erinaceus ) has a long history of usage in traditional Chinese medicine for the treatment of gastric disorders. Recently, it has become a well-established candidate in causing positive brain and nerve health-related activities by inducing nerve growth factor (NGF) from its bioactive ingredient, erinacine A. This active compound, which exists only in fermented mycelium but not in its fruiting body, increases NGF levels in astroglial cells in vitro as well as catecholamine and NGF levels in vivo . With increasing recognition of erinacine A in H. erinaceus (EAHE) mycelium improving neurodegenerative diseases, numerous products are being marketed based on these functional claims. To our knowledge, there have been no reports on the mutagenicity of EAHE prior to this paper. Hence, the present study was undertaken to determine the mutagenicity and genotoxicity effects of EAHE mycelium conducted in three standard battery of tests (reverse mutation, chromosomal aberration, and micronuclei tests) according to the latest guidelines in order to meet all international regulatory requirements and provide information on the safety of this new and promising natural remedy. Our results have indicated that EAHE mycelium did not significantly increase the number of revertant colonies in the bacterial reverse mutation test nor induce higher frequency of aberrations in the chromosome aberration test. Moreover, no statistically significant EAHE mycelium-related increase was observed in the incidence of reticulocytes per 1000 red blood cells and micronucleated reticulocytes per 1000 reticulocytes. In conclusion, the three standard battery of tests suggested that EAHE mycelium was devoid of mutagenicity and genotoxicity in the tested doses and experimental conditions.

Bacterial colonization of colonic crypt mucous gel and disease activity in ulcerative colitis.

LENUS (Irish Health Repository)

Rowan, Fiachra

2012-02-01

OBJECTIVE: To optimize total bacterial 16S rRNA quantification in microdissected colonic crypts in healthy controls and patients with ulcerative colitis (UC) and to characterize the findings with disease activity. BACKGROUND: Microscopic and molecular techniques have recently converged to allow bacterial enumeration in remote anatomic locations [eg, crypt-associated mucous gel (CAMG)]. The aims of this study were to combine laser capture microdissection (LCM) and 16S rRNA-based quantitative polymerase chain reaction (qPCR) to determine total bacterial copy number in CAMG both in health and in UC and to characterize the findings with disease activity. METHODS: LCM was used to microdissect CAMG from colonic mucosal biopsies from controls (n = 20) and patients with acute (n = 10) or subacute (n = 10) UC. Pan-bacterial 16S rRNA copy number per millimeter square in samples from 6 locations across the large bowel was obtained by qPCR using Desulfovibrio desulfuricans as a reference strain. Copy numbers were correlated with the UC disease activity index (UCDAI) and the simple clinical colitis activity index (SCCAI). RESULTS: Bacterial colonization of CAMG was detectable in all groups. Copy numbers were significantly reduced in acute UC. In subacute colitis, there was a positive correlation between copy number and UCDAI and SCCAI in the ascending, transverse and sigmoid colon. CONCLUSIONS: This study describes a sensitive method of quantitatively assessing bacterial colonization of the colonic CAMG. A positive correlation was found between CAMG bacterial load and subacute disease activity in UC, whereas detectable bacterial load was reduced in acute UC.

Multidetector CT of the colon

International Nuclear Information System (INIS)

Luboldt, W.; Hoepffner, N.; Holzer, K.

2003-01-01

Multidetector technology, enabling faster imaging, higher spatial resolution and reduction in radiation dose, increases the role of CT in colonic diagnostic. The higher spatial resolution in the z-direction also changes the way to analyze the images. Instead of reading axial sections, now the colon can be systematically assessed in 3D by scrolling through multiplanar reconstructions or in CT colonography by virtual endoscopy. With ongoing improvements in computer-aided diagnosis CT colonography becomes an alternative to fiberoptic colonocopy for screening (http://www.multiorganscreening.org). In this article we propose a CT examination protocol for the colon, describe the typical imaging findings of different colonic diseases, and summarize the current status of CT colonography. (orig.)

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

Directory of Open Access Journals (Sweden)

Roberta Nunes Horta

2016-03-01

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

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 commerci...... 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....

Protective effect of pumpkin seed oil against genotoxicity induced by azathioprine

OpenAIRE

Elfiky, S.A.; Elelaimy, I.A.; Hassan, A.M.; Ibrahim, H.M.; Elsayad, R.I.

2012-01-01

Pumpkin is a leafy green vegetable; it belongs to the Cucurbitaceae family. Pumpkin seed oil supplementation can prevent changes in plasma lipids and blood pressure. The present study was conducted to evaluate the protective effect of pumpkin seed oil against cytotoxicity and genotoxicity of azathioprine. Oral administration of pumpkin seed oil either before or after treatment of azathioprine was effective in the reduction of the frequencies of Mn-PCEs, decreased the DNA fragmentation, total ...