Sample records for observed mutagenic activity

  1. Mutagenic activity of disinfection by-products

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cognet, L.; Courtois, Y.; Mallevialle, J.

    1986-11-01

    Data on raw water quality, disinfection treatment practices, and the resulting mutagenic properties of the treated water were compiled from pilot- and full-scale treatment experiments to evaluate that parameter which might produce variability in the results of a mutagenic study. Analysis of the data and comparison of treatment practices indicated that the measured mutagenic activity is strongly related to the characteristics of the organic matter in the raw water, the methodology used to sample and detect mutagens, the scale of the study both in terms of treatment flow and period of study, and the point at which and the conditionsmore » under which oxidants are added during treatment. Conclusions regarding disinfection systems in full-scale water treatment plants include the following: When raw water is pretreated and high concentrations of organics are present in the raw water, both ozonation and chlorination increased mutagenic activity. However, no significant difference in mutagenicity was found between the two oxidants. Both in the case of a nitrified groundwater and a clarified surface water, the mutagenic activity of the water after ozonation was related to its mutagenic activity before ozonation. With ozonation, mutagenic activity decreased after granular activated carbon (GAC) filtration. Thus, when GAC filtration follows ozone disinfection, early addition of oxidants may not be deleterious to the finished water quality. When chlorine or chlorine dioxide is added after GAC filtration, chlorine dioxide was found to produce a less mutagenic water than chlorine. Although these conclusions suggest means of controlling mutagenic activity during treatment, it must be stressed that the measurement of mutagenicity is a presumptive index of contamination level.« less

  2. [Smoked sausages and food additives: evaluation of total mutagenic activity].

    PubMed

    Dugan, A M; Tkacheva, D L

    2011-01-01

    The paper deals with the evaluation of the total mutagenic activity of samples of the inorganic and organic fractions of three technology smoked sausages (boiled-smoked, semi-smoked, and raw-smoked) and some food additives used to manufacture the above sausages. Their mild and moderate mutagenic effects were recorded in a Salmonella typhimurium bacterial test system with a metabolic activation system. Physicochemical analysis of the fractions of the smoked sausages has shown that their study samples are substantially contaminated with heavy metals and representatives of polycyclic aromatic hydrocarbons, partially causing the mutagenic effects observed.

  3. Mutagenic activation reduces carcinogenic activity of ortho-aminoazotoluene for mouse liver.

    PubMed

    Ovchinnikova, L P; Bogdanova, L A; Kaledin, V I

    2013-03-01

    Pentachlorophenol (aromatic amine and azo stain metabolic stimulation inhibitor) reduced the hepatocarcinogenic activity of 4-aminoazobenzene and reduced that of ortho-aminoazotoluene in suckling mice. Both 4-aminoazobenzene and ortho-aminoazotoluene exhibited mutagenic activity in Ames' test in vitro on S. typhimurium TA 98 strain with activation with liver enzymes; this mutagenic activity was similarly suppressed by adding pentachlorophenol into activation medium. Induction of xenobiotic metabolism enzymes, stimulating the mutagenic activity of ortho-aminoazotoluene, suppressed its carcinogenic effect on mouse liver. Hence, ortho-aminotoluene (the initial compound), but not its mutagenic metabolites, was the direct active hepatocarcinogen for mice.

  4. Mutagenic activities of biochars from pyrolysis.

    PubMed

    Piterina, Anna V; Chipman, J Kevin; Pembroke, J Tony; Hayes, Michael H B

    2017-08-15

    Biochar production, from pyrolysis of lignocellulosic feedstocks, agricultural residues, and animal and poultry manures are emerging globally as novel industrial and commercial products. It is important to develop and to validate a series of suitable protocols for the ecological monitoring of the qualities and properties of biochars. The highly sensitive Salmonella mutagenicity assays (the Ames test) are used widely by the toxicology community and, via the rat liver extract (S9), can reflect the potential for mammalian metabolic activation. We examined the Ames test for analyses of the mutagenic activities of dimethylsulphoxide (DMSO) extracts of biochars using two bacterial models (S. typhimurium strains TA98 and TA100) in the presence and in the absence of the metabolic activation with the S9-mix. Tester strain TA98 was most sensitive in detecting mutagenic biochar products, and the contribution of S9 was established. Temperature and times of pyrolysis are important. Biochar pyrolysed at 400°C for 10min, from a lignocellulose precursor was mutagenic, but not when formed at 800°C for 60min, or at 600°C for 30min. Biochars from poultry litter, and manures of calves fed on grass had low mutagenicities. Biochar from pig manure had high mutagenicity; biochars from manures of cows fed on a grass plus cereals, those of calves fed on mother's milk, and biochars from solid industrial waste had intermediate mutagenicities. The methods outlined can indicate the need for further studies for screening and detection of the mutagenic residuals in a variety of biochar products. Copyright © 2017. Published by Elsevier B.V.

  5. Mutagenic activity of south Indian food items.

    PubMed

    Sivaswamy, S N; Balachandran, B; Balanehru, S; Sivaramakrishnan, V M

    1991-08-01

    Dietary components and food dishes commonly consumed in South India were screened for their mutagenic activity. Kesari powder, calamus oil, palm drink, toddy and Kewra essence were found to be strongly mutagenic; garlic, palm oil, arrack, onion and pyrolysed portions of bread toast, chicory powder were weakly mutagenic, while tamarind and turmeric were not. Certain salted, sundried and oil fried food items were also mutagenic. Cissus quadrangularis was mutagenic, while 'decoctions' of cumin seeds, aniseeds and ginger were not. Several perfumes, essential oils and colouring agents, which are commonly used were also screened and many of them exhibited their mutagenic potential by inducing the 'reverse mutation' in Salmonella typhimurium tester strains.

  6. Mutagenic activity of austocystins - secondary metabolites of Aspergillus ustus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kfir, R.; Johannsen, E.; Vleggaar, R.

    1986-11-01

    Mycotoxins constitute a group of toxic secondary fungal metabolites. Fungi that produce these toxins frequently contaminate food and feed, creating a potential threat to human and animal health. Biological activities of mycotoxins include, amongst others: toxicity, mutagenicity and carcinogenicity, which can be expressed with or without metabolic activation. Austocystins are similar in structure to aflatoxin B/sup 1/ and are probably synthesized in a similar manner. The Ames Salmonella test, a widely accepted method employed for the detection of mutagenic activity of various chemical compounds was used for testing the mutagenic activity of different mycotoxins. As aflatoxin B/sup 1/ was foundmore » by the Ames test to be highly mutagenic, the same test was applied for the study of possible mutagenicity of the austocystins. The mutagenic activity of these compounds was studied with and without metabolic activation using two tester strains of S. typhimurium, one capable of detecting frame shift mutation (strain TA98) and the other capable of detecting base pair substitution (strain TA100).« less

  7. Effects of diet composition on mutagenic activity in urine.

    PubMed

    Ohara, Akihiro; Matsuhisa, Tsugio

    2004-01-01

    The effects of dietary habits on mutagenic activity in urine were investigated using the umu test based on the use of the genetically engineered bacteria Salmonella typhimurium TA 1535 pSK1002. Genotoxic effects in sample urine were detected by measuring the activation of the SOS response in the bacteria and recording the beta- galactosidase activity. Human subjects consisted of smokers and non-smokers. Urine from subjects who consumed fish showed the highest mutagenic activity, followed by the urine samples from subjects who ate pork or beef. Chicken induced a low level of mutagenic activity. When the subjects ate fried or roasted animal foods, the urine samples gave higher mutagenicity than the urine samples from the subject who consumed non-fried or non-roasted animal foods. When the subject ate vegetables along with a diet rich in animal foods, the activity in urine decreased. Herbs and spices gave the same tendency toward decline as vegetables. Non-smoker urine shower mutagenic activity than samples from smokers.

  8. Mutagenic activity and heterocyclic amine content of heated foods

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Knize, M.G.; Johansson, M.; Jones, A.L.

    1994-12-31

    Cooked foods were extracted and analyzed for mutagenic activity and assayed for known heterocyclic amines (HAs) by the Ames/Salmonella test and HPLC, respectively. Fried meats contain HAs (predominantly PhIP, MeIQx, DiMeIQx, and A{alpha}C) that are potent promutagens in bacteria, mutagenic in cultured mammalian cells, and carcinogenic in rodents and in nonhuman primates. Meats contain levels ranging from undetectable (< 0.1 ppb) to 50 ppb of known HAs when fried at temperatures from 190 to 250{degrees}C. These identified compounds are responsible for ca 75% of the measured mutagenic activity in Salmonella strain TA98. Barbecued beef and chicken have up to severalmore » thousand TA98 revertants per gram (rev/g) of cooked meat, with only ca 30% of the mutagenic activity accounted for by known heterocyclic amines. Some heated nonmeat foods also contain potent mutagenic activity. Toasted breads, cereals and snack foods have 0 to 10 TA98 rev/g, but overtoasting yields up to 40 rev/g, wheat and gluten-containing products are associated with higher activity. Grain-based coffee-substitute powders and instant coffees have 190 to 380 rev/g in TA98, and 1100 to 4000 rev/g in strain YG1024. The identify of the compounds responsible for the mutagenic activity are unknown in these non-meat foods. Toasted grain-based foods probably contribute less than 10% of the total mutagenic activity of the diet, with meat products responsible for the reminder. The finding of varying amounts of known and unknown mutagens in some cooked foods may be responsible for the poorly understood variation in human cancer incidence worldwide.« less

  9. Mutagenic activity and heterocyclic amine content of the human diet

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Knize, M.G.; Dolbeare, F.A.; Cunningham, P.L.

    1993-01-15

    The mutagenic activity and the mass amount of heterocyclic amines responsible for the mutagenic activity have been measured in some cooked foods. Cooked meats are the predominant source of mutagenic activity in the diet with values ranging from 0 to 10,000 revertants per gram reported in the Ames/Salmonelia test with strain TA98. Several heterocyclic amines are present and have been quantified using solid-phase extraction followed by HPLC. Frying at higher temperatures and for longer times produces the greatest mutagenic response, and concomitantly, the largest amounts of heterocyclic amines. Most of the mutagenic activity in fried meat samples can be accountedmore » for by MelQx, DiMelQx and IQ, although other heterocylic amines are present and PHIP mutagenic activity becomes significant at higher temperatures. Non-meat products such as baked breads can also form significant mutagenic activity, particularly when overcooked. Commercially prepared hamburgers made from meat substitutes such as tofu, wheat gluten or tempeh and fried at 210{degrees}C have up to 10% of the mutagenic activity of a fried beef patty cooked under the same conditions. When detected, amounts of heterocyclic amines in fried beef patties range from a total of 0.35 ng/g for commercial beef hamburgers to 142 ng/g for a beef patty cooked over a barbecue. Dietary intake is expected to have a large range, from less than one microgram per day to over 50 micrograms per day based on current knowledge of known heterocyclic amine chemicals and heterocyclic amine-containing foods.« less

  10. Mutagenic activity of overnight urine from healthy non-smoking subjects.

    PubMed

    Pavanello, Sofia; Lupi, Silvia; Pulliero, Alessandra; Gregorio, Pasquale; Saia, Bruno Onofrio; Clonfero, Erminio

    2007-03-01

    Urinary mutagenicity was evaluated in relation to environmental mutagen exposure (i.e., diet, indoor/outdoor activities, residential area etc.) on the day prior to sample collection, and also considering factors that contribute to the variability of Salmonella mutagenicity assay results. Overnight urine samples from 283 healthy non-smoking residents of northeast Italy (46% males, 20-62 years) were analyzed for mutagenicity on sensitive Salmonella typhimurium strain YG1024 with S9 mix employing the preincubation version of the plate incorporation assay (i.e., the Salmonella reverse mutation test). Urinary mutagenicity varied between 0.02 and 9.84 rev/ equiv. ml, and 7% of samples were positive (i.e., sample elicited a two-fold increase in revertants). There was an evident increase in mutagenicity in subjects with increased intake of mutagen-rich meals (n = 80) (P < 0.01 and positive urine 13% vs. 5%, P = 0.025). Indoor-exposed subjects (n = 65) also showed a higher percentage of positive urine (14% vs. 5%, P = 0.015). In particular, those subjects exposed to cooking fumes the previous evening (n = 28) revealed higher urinary mutagenicity (P = 0.035, positive urine 25% vs. 5%, P < 0.001) than non-indoor exposed. The sources of variability of the mutagenicity assay, mainly the histidine content of the urine concentrate (z = 4.06, P < 0.0001), and to a lesser extent bacterial inoculum size (z = 2.33, P = 0.019), also significantly influenced urinary mutagenicity values. In a linear multiple regression analysis, their effects were still significant (i.e., histidine content P = 0.026 and inoculum size P = 0.021), but the effects of diet, indoor exposure, and other environmental exposures (i.e., traffic and heating system exhausts, residential area) were not. It is concluded that the previous day's exposure to mutagen-rich meals and cooking fumes may influence the presence of mutagenic activity in the overnight urine of non-smoking subjects. This mutagenic activity, which

  11. Mutagenic Activity of Indigofera truxillensis and I. suffruticosa Aerial Parts

    PubMed Central

    Calvo, Tamara Regina; Cardoso, Cássia Regina Primila; da Silva Moura, Adriana Candido; dos Santos, Lourdes Campaner; Colus, Ilce Mara Syllos; Vilegas, Wagner; Varanda, Eliana Aparecida

    2011-01-01

    Indigofera truxillensis and I. suffruticosa, are used as a source of indigo dye and to treat several diseases. The mutagenic activity of the methanolic extracts from aerial parts, glycerolipid, flavonoid and alkaloid fractions of the extract were evaluated by means of Salmonella/microsome assays using TA100, TA98, TA102 and TA97a strains. The methanolic extract of I. truxillensis showed mutagenic activity in the TA98 strain without S9 while glycerolipid fraction was devoid of activity. The flavonoid and alkaloid fractions of both plants showed mutagenicity. Chemical analysis of flavonoid fractions of I. truxillensis and I. suffruticosa resulted in the identification of kaempferol, quercetin and their derivatives. The alkaloid fraction of both the species contained indigo and indirubin and indigo was found mainly responsible for the mutagenic activity. PMID:19696193

  12. Evaluation of antioxidant and mutagenic activities of honey-sweetened cashew apple nectar.

    PubMed

    da Silva, Robson Alves; Dihl, Rafael Rodrigues; Nascimento e Santos, Débora; de Abreu, Bianca Regina Ribas; de Lima, Alessandro; de Andrade, Heloisa Helena Rodrigues; Lehmann, Mauricio

    2013-12-01

    In vitro chemical properties and antioxidant potential and in vivo mutagenic activity of honey-sweetened cashew apple nectar (HSCAN), a beverage produced from the cashew pseudo-fruit (Anacardium occidentale L.) and of its constituents were assessed. Analytical procedures were carried out to investigate the honey used in the HSCAN preparation, and the results observed are in accordance with Brazilian legal regulations, except for diastase number. HSCAN and pulp were investigated for ascorbic acid, carotenoid, anthocyanin and total phenolic contents, and both showed high acid ascorbic concentrations. Antioxidant capacity using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and/or β-carotene/linoleic acid systems were applied and demonstrated a weak antioxidant capacity of honey and HSCAN, but cashew apple pulp demonstrated high antioxidant capacity. A weakly positive mutagenic effect of cashew pulp 20% was observed using the somatic mutation and recombination test (SMART) in Drosophila melanogaster only in the high-bioactivation (HB) cross. On the contrary, HSCAN was not mutagenic in both standard and high bioactivation crosses. HSCAN exhibited slight antioxidant activity, which could be associated with the high amount of ascorbic acid found in the samples evaluated. The beverage prepared did not induce DNA damage in somatic cells of D. melanogaster, which means that it is neither mutagenic nor recombinagenic in this test system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Comparison of Mutagenic Activities of Various Ultra-Fine Particles.

    PubMed

    Park, Chang Gyun; Cho, Hyun Ki; Shin, Han Jae; Park, Ki Hong; Lim, Heung Bin

    2018-04-01

    Air pollution is increasing, along with consumption of fossil fuels such as coal and diesel gas. Air pollutants are known to be a major cause of respiratory-related illness and death, however, there are few reports on the genotoxic characterization of diverse air pollutants in Korea. In this study, we investigated the mutagenic activity of various particles such as diesel exhaust particles (DEP), combustion of rice straw (RSC), pine stem (PSC), and coal (CC), tunnel dust (TD), and road side dust (RD). Ultra-fine particles (UFPs) were collected by the glass fiber filter pad. Then, we performed a chemical analysis to see each of the component features of each particulate matter. The mutagenicity of various UFPs was determined by the Ames test with four Salmonella typhimurium strains with or without metabolic activation. The optimal concentrations of UFPs were selected based on result of a concentration decision test. Moreover, in order to compare relative mutagenicity among UFPs, we selected and tested DEP as mutation reference. DEP, RSC, and PSC induced concentration-dependent increases in revertant colony numbers with TA98, TA100, and TA1537 strains in the absence and presence of metabolic activation. DEP showed the highest specific activity among the particulate matters. In this study, we conclude that DEP, RSC, PSC, and TD displayed varying degrees of mutagenicity, and these results suggest that the mutagenicity of these air pollutants is associated with the presence of polycyclic aromatic hydrocarbons (PAHs) in these particulate matters.

  14. Mutagenicity in emissions from coal- and oil-fired boilers.

    PubMed Central

    Alfheim, I; Bergström, J G; Jenssen, D; Møller, M

    1983-01-01

    The mutagenicity of emission samples from three oil-fired and four coal-fired boilers have been compared by using the Salmonella/microsome assay. Very little or no mutagenic activity was observed in samples from five of these boilers. The sample from one oil-fired boiler showed mutagenic activity of about 500 revertants/MJ, and the sample from a coal-fired fluidized bed combustor had an activity of 58,000 revertants/MJ measured with strain TA 98 in the absence of metabolic activation. All samples contained substances that were cytotoxic to the test bacteria, thus making it difficult to obtain linear dose-response curves. Mutagenic activity at low levels may remain undetected due to this toxicity of the samples. Samples with mutagenic activity below the detection limit in the Salmonella test have also been tested for forward mutations at the HGPRT locus in V79 hamster cells. Weak mutagenic effects were detected in two of the samples, whereas the sample from one oil-fired boiler remained negative. In this test, as well as in the Salmonella test, a strong cytotoxic effect could be observed with all samples. PMID:6825617

  15. Mutagenicity studies in a tyre plant: in-vitro activity of urine concentrates and rubber chemicals.

    PubMed

    Crebelli, R; Falcone, E; Aquilina, G; Carere, A; Paoletti, A; Fabri, G

    1984-01-01

    A possible occupational contribution to urinary mutagenicity was studied in a tyre plant, by assaying concentrates of urine from 72 workmen and 23 controls for their activity in the Ames test and microtitre fluctuation test. The results show that smoking habits but not occupation are related to the appearance of a detectable urinary mutagenicity in strain TA98. A possible synergistic effect of occupation was, however, observed among tyre builders who were smokers. Mutagenicity screening of 25 rubber chemicals, of major technological relevance and used in high volume in the workplace investigated, showed that three of them are weakly active in TA98 and TA100 (tetramethylthiuram disulfide) or TA98 alone (poly-p-dinitrosobenzene and mixed diaryl-p-phenylendiamines).

  16. Role of ozone and granular activated carbon in the removal of mutagenic compounds.

    PubMed Central

    Bourbigot, M M; Hascoet, M C; Levi, Y; Erb, F; Pommery, N

    1986-01-01

    The identification of certain organic compounds in drinking water has led water treatment specialists to be increasingly concerned about the eventual risks of such pollutants to the health of consumers. Our experiments focused on the role of ozone and granular activated carbon in removing mutagenic compounds and precursors that become toxic after chlorination. We found that if a sufficient dose of ozone is applied, its use does not lead to the creation of mutagenic compounds in drinking water and can even eliminate the initial mutagenicity of the water. The formation of new mutagenic compounds seems to be induced by ozonation that is too weak, although these mutagens can be removed by GAC filtration. Ozone used with activated carbon can be one of the best means for eliminating the compounds contributing to the mutagenicity of water. A combined treatment of ozone and activated carbon also decreases the chlorine consumption of the treated water and consequently reduces the formation of chlorinated organic compounds. PMID:3816720

  17. Characterization and Quantification of Compounds in the Hydroalcoholic Extract of the Leaves from Terminalia catappa Linn. (Combretaceae) and Their Mutagenic Activity

    PubMed Central

    Mininel, Francisco José; Leonardo Junior, Carlos Sérgio; Espanha, Lívia Greghi; Resende, Flávia Aparecida; Varanda, Eliana Aparecida; Leite, Clarice Queico Fujimura; Vilegas, Wagner; dos Santos, Lourdes Campaner

    2014-01-01

    Terminalia is a genus of Combretaceous plants widely distributed in tropical and subtropical regions. Thus, the aim of this study was to quantify the majority compounds of the hydroalcoholic extract (7 : 3, v/v) of the leaves from T. catappa by HPLC-PDA, chemically characterize by hyphenated techniques (HPLC-ESI-IT-MSn) and NMR, and evaluate its mutagenic activity by the Salmonella/microsome assay on S. typhimurium strains TA98, TA97a, TA100, and TA102. The quantification of analytes was performed using an external calibration standard. Punicalagin is the most abundant polyphenol found in the leaves. The presence of this compound as a mixture of anomers was confirmed using HPLC-PDA and 1H and 13C NMR. Mutagenic activity was observed in strains TA100 and TA97a. As the extract is a complex mixture of punicalagin, its derivatives, and several other compounds, the observed mutagenicity may be explained in part by possible synergistic interaction between the compounds present in the extract. These studies show that mutagenic activity of T. catappa in the Ames test can only be observed when measured at high concentrations. However, considering the mutagenic effects observed for T. catappa, this plant should be used cautiously for medicinal purposes. PMID:24734110

  18. Characterization of mutagenic activity in grain-based coffee-substitute blends and instant coffees

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Johansson, M.A.E.; Knize, M.G.; Felton, J.S.

    1994-06-01

    Several grain-based coffee-substitute blends and instant coffees showed a mutagenic response in the Ames/Salmonella test using TA98, YG1024 and YG1O29 with metabolic activation. The beverage powders contained 150 to 500 TA98 and 1150 to 4050 YG1024 revertant colonies/gram, respectively. The mutagenic activity in the beverage powders was shown to be stable to heat and the products varied in resistance to acid nitrite treatment. Characterization of the mutagenic activity, using HPLC-and the Ames test of the collected fractions, showed the coffee-substitutes and instant coffees contain several mutagenic compounds, which are most likely aromatic amines.

  19. Fecalase: a model for activation of dietary glycosides to mutagens by intestinal flora

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tamura, G.; Gold, C.; Ferro-Luzzi, A.

    1980-08-01

    Many substances in the plant kingdom and in man's diet occur as glycosides. Recent studies have indicated that many glycosides that are not mutagenic in tests such as the Salmonella test become mutagenic upon hydrolysis of the glycosidic linkages. The Salmonella test utilizes a liver homogenate to approximate mammalian metabolism but does not provide a source of the enzymes present in intestinal bacterial flora that hydrolyze the wide variety of glycosides present in nature. We describe a stable cell-free extract of human feces, fecalase, which is shown to contain various glycosidases that allow the in vitro activation of many naturalmore » glycosides to mutagens in the Salmonella/liver homogenate test. Many beverages, such as red wine (but apparently not white wine) and tea, contain glycosides of the mutagen quercetin. Red wine, red grape juice, and teas were mutagenic in the test when fecalase was added, and red wine contained considerable direct mutagenic activity in the absence of fecalase. The implications of quercetin mutagenicity and carcinogenicity are discussed.« less

  20. Mutagenicity studies in a tyre plant: in vitro activity of workers' urinary concentrates and raw materials.

    PubMed

    Crebelli, R; Paoletti, A; Falcone, E; Aquilina, G; Fabri, G; Carere, A

    1985-07-01

    The possible contribution to urinary mutagenicity of occupational exposures in the rubber industry was studied by assaying the urine concentrates of 72 workmen (44 smokers) employed in a tyre plant. Twenty three clerks (16 smokers) engaged in the administrative department of the same factory served as presumptive unexposed controls. XAD-2 resin concentrates of urine samples were assayed in the plate incorporation test and in the microtitre fluctuation assay with Salmonella typhimurium strains TA1535, TA98, and TA100. Furthermore, the in vitro mutagenicity of the major raw materials in use at the plant was determined in the plate incorporation assay with S typhimurium strains TA1535, TA1537, TA98, and TA100. The results obtained from the urinary mutagenicity study show that smoking habits, but not occupation, were statistically significantly related to the appearance of a urinary mutagenicity that was detectable with strain TA98. A possible synergistic effect of occupation with smoking was observed among tyre builders who were also smokers. The study of the raw materials showed that three technical grade materials were weakly active as mutagens in strain TA98 in the absence (poly-p-dinitrosobenzene) or in the presence of metabolic activation (mixed diaryl-p-phenylendiamines and tetramethyltiuram disulphide). The latter chemical was also weakly active in strain TA100.

  1. Mutagenicity studies in a tyre plant: in vitro activity of workers' urinary concentrates and raw materials.

    PubMed Central

    Crebelli, R; Paoletti, A; Falcone, E; Aquilina, G; Fabri, G; Carere, A

    1985-01-01

    The possible contribution to urinary mutagenicity of occupational exposures in the rubber industry was studied by assaying the urine concentrates of 72 workmen (44 smokers) employed in a tyre plant. Twenty three clerks (16 smokers) engaged in the administrative department of the same factory served as presumptive unexposed controls. XAD-2 resin concentrates of urine samples were assayed in the plate incorporation test and in the microtitre fluctuation assay with Salmonella typhimurium strains TA1535, TA98, and TA100. Furthermore, the in vitro mutagenicity of the major raw materials in use at the plant was determined in the plate incorporation assay with S typhimurium strains TA1535, TA1537, TA98, and TA100. The results obtained from the urinary mutagenicity study show that smoking habits, but not occupation, were statistically significantly related to the appearance of a urinary mutagenicity that was detectable with strain TA98. A possible synergistic effect of occupation with smoking was observed among tyre builders who were also smokers. The study of the raw materials showed that three technical grade materials were weakly active as mutagens in strain TA98 in the absence (poly-p-dinitrosobenzene) or in the presence of metabolic activation (mixed diaryl-p-phenylendiamines and tetramethyltiuram disulphide). The latter chemical was also weakly active in strain TA100. PMID:4015996

  2. Origanum majorana Essential Oil Lacks Mutagenic Activity in the Salmonella/Microsome and Micronucleus Assays

    PubMed Central

    Klein-Júnior, Luiz Carlos; Guecheva, Temenouga N.; dos Santos, Luciana D.; Zanette, Régis A.; de Mello, Fernanda B.; de Mello, João Roberto Braga

    2016-01-01

    The present study aimed to investigate the in vitro mutagenic activity of Origanum majorana essential oil. The most abundant compounds identified by GC-MS were γ-terpinene (25.73%), α-terpinene (17.35%), terpinen-4-ol (17.24%), and sabinene (10.8%). Mutagenicity was evaluated by the Salmonella/microsome test using the preincubation procedure on TA98, TA97a, TA100, TA102, and TA1535 Salmonella typhimurium strains, in the absence or in the presence of metabolic activation. Cytotoxicity was detected at concentrations higher than 0.04 μL/plate in the absence of S9 mix and higher than 0.08 μL/plate in the presence of S9 mix and no gene mutation increase was observed. For the in vitro mammalian cell micronucleus test, V79 Chinese hamster lung fibroblasts were used. Cytotoxicity was only observed at concentrations higher than or equal to 0.05 μg/mL. Moreover, when tested in noncytotoxic concentrations, O. majorana essential oil was not able to induce chromosome mutation. The results from this study therefore suggest that O. majorana essential oil is not mutagenic at the concentrations tested in the Salmonella/microsome and micronucleus assays. PMID:27891531

  3. Mutagenicity of benzotrichloride and related compounds.

    PubMed

    Yasuo, K; Fujimoto, S; Katoh, M; Kikuchi, Y; Kada, T

    1978-11-01

    Benzotrichloride (BTC), benzal chloride (BDC), benzyl chloride (BC) and benzoyl chloride (BOC) were surveyed for their mutagenicity in microbial systems such as rec-assay using Bacillus subtilis and reversion assays using E. coli WP2 and Ames Salmonella TA strains with or without metabolic activation in vitro. BTC and BDC required metabolic activation for their mutagenic activities in several strains of E. coli and Salmonella. The mutagenic metabolites of these compounds may not have been produced by hydrolysis. BC was weakly mutagenic without metabolic activation. Only BOC exhibited no mutagenic activity in the detection procedures used. The mutagenic metabolite of BTC might be very unstable under our experimental conditions. The strain E. coli WP2 try hcr was more sensitive than E. coli B/r WP2 try (hcr+) with regard to the mutagenicity of BTC.

  4. Mutagenicity in a Molecule: Identification of Core Structural Features of Mutagenicity Using a Scaffold Analysis

    PubMed Central

    Hsu, Kuo-Hsiang; Su, Bo-Han; Tu, Yi-Shu; Lin, Olivia A.; Tseng, Yufeng J.

    2016-01-01

    With advances in the development and application of Ames mutagenicity in silico prediction tools, the International Conference on Harmonisation (ICH) has amended its M7 guideline to reflect the use of such prediction models for the detection of mutagenic activity in early drug safety evaluation processes. Since current Ames mutagenicity prediction tools only focus on functional group alerts or side chain modifications of an analog series, these tools are unable to identify mutagenicity derived from core structures or specific scaffolds of a compound. In this study, a large collection of 6512 compounds are used to perform scaffold tree analysis. By relating different scaffolds on constructed scaffold trees with Ames mutagenicity, four major and one minor novel mutagenic groups of scaffold are identified. The recognized mutagenic groups of scaffold can serve as a guide for medicinal chemists to prevent the development of potentially mutagenic therapeutic agents in early drug design or development phases, by modifying the core structures of mutagenic compounds to form non-mutagenic compounds. In addition, five series of substructures are provided as recommendations, for direct modification of potentially mutagenic scaffolds to decrease associated mutagenic activities. PMID:26863515

  5. Mutagenicity of an aged gasworks soil during bioslurry treatment

    PubMed Central

    Lemieux, Christine L; Lynes, Krista D; White, Paul A; Lundstedt, Staffan; Öberg, Lars; Lambert, Iain B

    2009-01-01

    This study investigated changes in the mutagenic activity of organic fractions from soil contaminated with polycyclic aromatic hydrocarbons (PAHs) during pilot-scale bioslurry remediation. Slurry samples were previously analyzed for changes in PAH and polycyclic aromatic compound content, and this study examined the correspondence between the chemical and toxicological metrics. Nonpolar neutral and semipolar aromatic fractions of samples obtained on days 0, 3, 7, 24, and 29 of treatment were assayed for mutagenicity using the Salmonella mutation assay. Most samples elicited a significant positive response on Salmonella strains TA98, YG1041, and YG1042 with and without S9 metabolic activation; however, TA100 failed to detect mutagenicity in any sample. Changes in the mutagenic activity of the fractions across treatment time and metabolic activation conditions suggests a pattern of formation and transformation of mutagenic compounds that may include a wide range of PAH derivatives such as aromatic amines, oxygenated PAHs, and S-heterocyclic compounds. The prior chemical analyses documented the formation of oxygenated PAHs during the treatment (e.g., 4-oxapyrene-5-one), and the mutagenicity analyses showed high corresponding activity in the semipolar fraction with and without metabolic activation. However, it could not be verified that these specific compounds were the underlying cause of the observed changes in mutagenic activity. The results highlight the need for concurrent chemical and toxicological profiling of contaminated sites undergoing remediation to ensure elimination of priority contaminants as well as a reduction in toxicological hazard. Moreover, the results imply that remediation efficacy and utility be evaluated using both chemical and toxicological metrics. Environ. Mol. Mutagen. 2009. © 2009 Wiley-Liss, Inc. PMID:19274766

  6. Di-epoxides of the three isomeric dicyclopenta-fused pyrenes: ultimate mutagenic active agents.

    PubMed

    Otero-Lobato, María José; Kaats-Richters, Veronica E M; Havenith, Remco W A; Jenneskens, Leonardus W; Seinen, Willem

    2004-11-14

    To rationalize the high bacterial mutagenic response recently found for the (di-) cyclopenta-fused pyrene congeners, viz. cyclopenta[cd]-(1), dicyclopenta[cd,mn]-(2), dicyclopenta[cd,fg]-(3) and dicyclopenta[cd,jk]pyrene (4), in the presence of a metabolic activation mixture (S9-mix), their (di-)epoxides at the externally fused unsaturated five-membered rings were previously proposed as the ultimate mutagenic active forms. In this study, cyclopenta[cd]pyrene-3,4-epoxide (5) and the novel dicyclopenta[cd,mn]pyrene-1,2,4,5-di-epoxide (6), dicyclopenta[cd,fg]pyrene-5,6,7,8-di-epoxide (7) and dicyclopenta[cd,jk]pyrene-1,2,6,7-di-epoxide (8) were synthesised from 1 to 4, respectively, and subsequently assayed for bacterial mutagenicity in the standard microsomal/histidine reverse mutation assay (Ames-assay with Salmonella typhimurium strain TA98). The di-epoxides 6-8 are present as a mixture of their cis- and trans-stereo-isomers in a close to 1:1 ratio ((1)H NMR spectroscopy and ab initio IGLO/III//RHF/6-31G** calculations). The direct-acting mutagenic activity and the strong cytotoxicity exerted by 5-8 both in the absence or presence of an exogenous metabolic activation system (+/-S9-mix) demonstrate that the ultimate mutagenic active forms are the proposed (di-)epoxides of 1-4.

  7. Mutagenic activity and metabolites in the urine of workers exposed to trinitrotoluene (TNT).

    PubMed Central

    Ahlborg, G; Einistö, P; Sorsa, M

    1988-01-01

    Urine samples taken after work and after a free weekend from 50 workers employed in various activities in a chemical plant manufacturing explosives were analysed. On the basis of hygienic surveys, the subjects were divided into three categories of exposure to trinitrotoluene (TNT). The urine analyses consisted of gas chromatographic identification of TNT and its two metabolites, 4-ADNT and 2-ADNT, and a determination of the mutagenic activity. Two frame shift detector strains of Salmonella typhimurium were used, TA 98 and TA 98 NR, the latter being deficient in endogenous nitroreductase activity. On the basis of previous results on TNT mutagenicity, no exogeneous metabolic system was used to test the urine concentrates. Both tester strains showed that the mean urinary mutagenic activity was higher in the after work samples than in post weekend samples from the same subjects, showing that bacterial nitroreductase activity was not significantly responsible for the mutagenicity, although the response was higher with strain TA 98 than with TA 98 NR. The interindividual variation in urine mutagenicity was high, however, and the difference between the two sampling times was statistically significant (p less than 0.05) only for the high exposed group (workers in trotyl foundry and sieve house). Correlation between urinary mutagenicity and concentration of TNT in urine was poor; correlation was significant only with the urinary concentration of 4-ADNT. The correlation between urinary TNT and both metabolites was good (p less than 0.001). These results suggest that analysis of 4-ADNT in urine would be a sufficient biological measure for controlling exposure to TNT. PMID:3378017

  8. Exposure related mutagens in urine of rubber workers associated with inhalable particulate and dermal exposure

    PubMed Central

    Vermeulen, R; Bos, R; Pertijs, J; Kromhout, H

    2003-01-01

    Aims: To determine the relation of the inhalation and dermal exposure routes and mutagenic activity in the urine of rubber workers (n = 105). Methods: Mutagenic activity of ambient total suspended particulate matter (TSPM), surface contamination wipes, and Sunday and weekday urine samples was assessed with S typhimurium YG1041 in the presence of a metabolic activation system. Each subject was grouped into one of two exposure categories for dermal exposure (high (≥25 revertants/cm2), low (<25 revertants/cm2)) based on the mutagenic activity detected on likely skin contact surfaces and into two airborne mutagenic exposure categories (high (≥210 revertants/m3), low (<210 revertants/m3)). The potential influence of skin aberrations and acetylation status (NAT2) on urinary mutagenicity levels was also evaluated. Results: A non-significant increase of +1605 revertants/g creatinine in urinary mutagenicity during the workweek relative to levels observed on Sunday was observed for the total population. Subsequent multivariate regression analyses, with the subjects' weekday urinary mutagenicity levels as the dependent variable, revealed associations with environmental and mainstream tobacco smoke exposure, with the level of mutagenic contamination on surfaces with which the subjects had likely contact, with the subjects' inhalable particulate exposure level, with observed mild skin aberrations, and when the subjects had a slow acetylation phenotype. Similar associations, although weaker were observed with Sunday urinary mutagenicity levels as well, except for the association with slow acetylation phenotype. Based on measured exposure levels it could be estimated that a high potential for exposure to surface contamination with mutagenic activity increased weekday urinary mutagenicity by about 62% when compared to low exposed workers, while high inhalable particulate exposure levels increased weekday urinary mutagenicity levels by about 21%. Subjects with mild skin

  9. Mutagenic activities of a chlorination by-product of butamifos, its structural isomer, and their related compounds.

    PubMed

    Kamoshita, Masahiro; Kosaka, Koji; Endo, Osamu; Asami, Mari; Aizawa, Takako

    2010-01-01

    The mutagenic activities of 5-methyl-2-nitrophenol (5M2NP), a chlorination by-product of butamifos, its structural isomer 2-methyl-5-nitrophenol (2M5NP), and related compounds were evaluated by the Ames assay. The mutagenic activities of 5M2NP and 2M5NP were negative or not particularly high. However, those of their chlorinated derivatives were increased in Salmonella typhimurium strain TA100 and the overproducer strains YG1026, and YG1029 in the absence and/or presence of a rat liver metabolic activation system (S9 mix), particularly for YG1029. The mutagenic activities of 6-chloro-2-methyl-5-nitrophenol (6C2M5NP) in YG1029 in the absence and presence of S9 mix were 70000 and 110000 revertants mg(-1), respectively. When nitro functions of 6C2M5NP and 4-chloro-5-methyl-2-nitrophenol (4C5M2NP) were reduced to amino functions, their mutagenic activities were markedly decreased. The mutagenic activities of 5M2NP and 4C5M2NP were lower than those of 2M5NP and 6C2M5NP, respectively. Thus, it was shown that substituent position is a key factor for the mutagenic activities of methylnitrophenols (MNPs) and related compounds. The mutagenic activities of the extracts of 2M5NP in chlorination increased early during the reaction time and then decreased. The main chlorination by-product contributing to the mutagenic activities of the extracts of 2M5NP in chlorination was 6C2M5NP. The results of chlorination of 2M5NP suggested that MNPs were present as their dichlorinated derivatives or further chlorination by-products in drinking water. Copyright 2009 Elsevier Ltd. All rights reserved.

  10. Mutagenicity of diesel exhaust particles from an engine with differing exhaust after treatments.

    PubMed

    Shi, X-C; Keane, M J; Ong, T; Li, S-Q; Bugarski, A B

    2010-01-01

    This study was conducted to investigate the effects of engine operating conditions and exhaust aftertreatments on the mutagenicity of diesel particulate matter (DPM) collected directly in an underground mine environment. A number of after-treatment devices are currently used on diesel engines in mines, but it is critical to determine whether reductions in DPM concentrations result in a corresponding decrease in adverse health effects. An eddy-current dynamometer was used to operate naturally aspirated mechanically controlled engine at several steady-state conditions. The samples were collected when the engine was equipped with a standard muffler, a diesel oxidation catalytic converter, two types of uncatalyzed diesel particulate filter systems, and three types of disposable diesel particulate filter elements. Bacterial gene mutation activity of DPM was tested on acetone extracts using the Ames Salmonella assay. The results indicated strong correlation between engine operating conditions and mutagenic activity of DPM. When the engine was fitted with muffler, the mutagenic activity was observed for the samples collected from light-load, but not heavy-load operating conditions. When the engine was equipped with a diesel oxidation catalyst, the samples did not exhibit mutagenic activity for any of four engine operating conditions. Mutagenic activity was observed for the samples collected when the engine was retrofitted with three types of disposable filters and sintered metal diesel particulate filter and operated at light load conditions. However, those filtration systems substantially reduced the concentration-normalized mutagenic activity from the levels observed for the muffler.

  11. Alphatic 3,4-epoxyalcohols. Metabolism by epoxide hydrase and mutagenic activity.

    PubMed

    Ortiz de Montellano, P R; Boparai, A S

    1978-12-18

    Rabbit hepatic microsomal epoxide hydrase catalyzes the rapid hydrolysis of 1,2-epoxy-4-heptanol to 1,2,4-heptanetriol. Both diastereomers of the substrate are hydrolyzed, and both product diastereomers are formed. Similarly both cis- and trans-3,4-epoxy-1-hexanol are hydrolyzed, albeit more slowly, to give 1,3,4-hexanetriol. The trans isomer gives exclusively one diastereomer (erythro) of the triol, while the cis isomer gives the other diastereomer (threo). The product expected if a primary cationic intermediate were to be formed and trapped intramolecularly during the hydrolysis of 1,2-epoxy-4-heptanol, 2-propyl-4-tetrahydrofuranol, was not observed. A comparison of the mutagenic activity in the Ames test of 1-heptane, 1-hepten-4-ol, 1,2-epoxyheptane, and 1,2-epoxy-4-heptanol revealed that only the latter is a detectable mutagen. A vicinal hydroxyl therefore does not interfere significantly with enzymatic epoxide hydrolysis, but it does enhance the bioalkylating potential of even an aliphatic epoxide.

  12. Inhibitory effects of neem seed oil and its extract on various direct acting and activation-dependant mutagens-induced bacterial mutagenesis.

    PubMed

    Vijayan, Vinod; Tiwari, Pramod Kumar; Meshram, Ghansham Pundilikji

    2013-12-01

    Azadirachta indica A. Juss (Meliaceae), commonly called neem is a plant native to the Indian sub-continent. Neem oil extracted from the seeds of neem tree has shown promising medicinal properties. To investigate the possible anti-mutagenic activity of neem seed oil (NO) and its dimethylsulfoxide (DMSO) extract (NDE) on the mutagenicity induced by various direct acting and activation-dependant mutagens. The possible anti-mutagenic activity of NO (100-10,000 µg/plate) and NDE (0.1-1000 µg/plate) as well as the mechanism of anti-mutagenic activity was studied in an in vitro Ames Salmonella/microsome assay. NSO and NDE inhibited the mutagenic activity of methyl glyoxal (MG), in which case the extent of inhibition ranged from 65 to 77% and against 4-nitroquinoline-N-oxide (NQNO); it showed a 48-87% inhibition in the non-toxic doses. Similar response of NSO and NDE was seen against the activation-dependant mutagens aflatoxin B1 (AFB1, 48-88%), benzo(a)pyrene (B(a)P, 31-85%), cyclophosphamide (CP, 66-71%), 20-methylcholanthrane (20-MC, 37-83%) and acridine orange (AO, 39-72%) in the non-toxic doses. Mechanism-based studies indicated that NDE exhibits better anti-mutagenic activity in the pre- and simultaneous-treatment protocol against MG, suggesting that one or several active phytochemicals present in the extract covalently bind with the mutagen and prevent its interaction with the genome. These findings demonstrate that neem oil is capable of attenuating the mutagenic activity of various direct acting and activation-dependant mutagens.

  13. Mutagenic activities of heterocyclic amines in Chinese hamster lung cells in culture

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Terada, M.; Nagao, M.; Nakayasu, M.

    1986-01-01

    A mutation assay system with Chinese hamster lung cells (CHL) using diphtheria toxin resistance as a selective marker has been established. The mutagenic activities of heterocyclic amines, originally isolated from pyrolyzates of amino acids and proteins, broiled fish and fried beef were assayed in cultured CHL cells in the absence and presence of a metabolic activation system, with diphtheria toxin resistance as a marker. All the heterocyclic amines tested except 3-amino-1,4-dimethyl-5H-pyrido (4,3-b)indole (Trp-P-1) required the presence of a metabolic activation system for mutagenicity on CHL cells. 3-Amino-1-methyl-5H-pyrido(4,3-b)indole (Trp-P-2) was the most mutagenic among the heterocyclic amines tested. Other compounds weremore » also mutagenic in the following order of decreasing potency: Trp-P-1, 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ), 2-amino-3-methylimidazo(4,5-f)quinoline (IQ), 2-amino-9H-pyrido(2,3-b)indole (A..cap alpha..C), 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx), 2-amino-6-methyldipyrido(1,2-a:3',2'-d)imidazole (Glu-P-1) and 2-aminodipyrido(1,2--a:3',2'-d)imidazole (Glu-P-2).« less

  14. Screening complex hazardous wastes for mutagenic activity using a modified version of the TLC/Salmonella assay.

    PubMed

    Houk, V S; Claxton, L D

    1986-03-01

    10 complex hazardous wastes were tested for mutagenic activity using a modified version of the TLC/Salmonella assay developed by Bjørseth et al. (1982). This fractionation/bioassay scheme couples thin-layer chromatography (TLC) with the Salmonella/mammalian-microsome (Ames) assay for the detection of mutagenic constituents in complex mixtures. Crude (unadulterated) hazardous wastes and selected hazardous waste extracts were fractionated on commercially available cellulose TLC plates. Mutagenicity testing was performed in situ by applying a single overlay of minimal growth agar, tester strain TA98 or TA100, and the optional metabolic activation system directly onto the developed chromatogram. A mutagenic effect was indicated either by the appearance of localized clusters of revertant colonies or by an increase in total revertant growth vis-à-vis control plates. 7 of 10 hazardous wastes (including tars, emulsions, sludges, and spent acids and caustics) demonstrated mutagenic activity when tested by this method. To assess the sensitivity of the modified TLC/Salmonella assay, 14 Salmonella mutagens from a wide range of chemical classes and polarities were tested. Selected compounds included heterocyclics, aromatic amines, alkylating agents, antitumor agents, a nitrosamine and a nitroaromatic. 11 of the 14 mutagens were positive in this test system. The 3 compounds refractory to analysis included a polycyclic aromatic hydrocarbon and two volatiles.

  15. Formation of mutagens in cooked foods. I. Beef.

    PubMed

    Spingarn, N E; Weisburger, J H

    1979-09-01

    Mutagens detectable by Salmonella typhimurium TA98, after activation by liver S-9 fraction, are formed when meat is cooked by frying, broiling and boiling. High levels of mutagenic activity are formed rapidly when frying, or more slowly during broiling. Formation of mutagens in boiled beef stock requires several days under reflux, but shows a strong concentration dependence. Time curves suggest that a period exists during which mutagens are not readily formed; however, after this period mutagen production is rapid. Hamburgers from commercial franchises were frequently mutagenically active.

  16. Dietary Mutagen Exposure and Risk of Pancreatic Cancer

    PubMed Central

    Li, Donghui; Sue Day, Rena; Bondy, Melissa L.; Sinha, Rashmi; Nguyen, Nga T.; Evans, Douglas B.; Abbruzzese, James L.; Hassan, Manal M.

    2007-01-01

    To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. Atotal of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (±5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases than controls showed a preference to well-done pork, bacon, grilled chicken, and pan-fried chicken, but not to hamburger and steak. Cases had a higher daily intake of food mutagens and mutagenicity activity (revertants per gram of daily meat intake) than controls did. The daily intakes of 2-amino-3,4,8-trimethylimidazo[4,5—f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP), as well as the mutagenic activity, were significant predictors for pancreatic cancer (P = 0.008, 0.031, and 0.029, respectively) with adjustment of other confounders. A significant trend of elevated cancer risk with increasing DiMeIQx intake was observed in quintile analysis (Ptrend= 0.024). Ahigher intake of dietary mutagens (those in the two top quintiles) was associated with a 2-fold increased risk of pancreatic cancer among those without a family history of cancer but not among those with a family history of cancer. Apossible synergistic effect of dietary mutagen exposure and smoking was observed among individuals with the highest level of exposure (top 10%) to PhIP and BaP, Pinteraction= 0.09 and 0.099, respectively. These data support the hypothesis that dietary mutagen exposure alone and in interaction with other factors contribute to the development of pancreatic cancer. PMID:17416754

  17. Dietary mutagen exposure and risk of pancreatic cancer.

    PubMed

    Li, Donghui; Day, Rena Sue; Bondy, Melissa L; Sinha, Rashmi; Nguyen, Nga T; Evans, Douglas B; Abbruzzese, James L; Hassan, Manal M

    2007-04-01

    To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. A total of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (+/-5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases than controls showed a preference to well-done pork, bacon, grilled chicken, and pan-fried chicken, but not to hamburger and steak. Cases had a higher daily intake of food mutagens and mutagenicity activity (revertants per gram of daily meat intake) than controls did. The daily intakes of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP), as well as the mutagenic activity, were significant predictors for pancreatic cancer (P = 0.008, 0.031, and 0.029, respectively) with adjustment of other confounders. A significant trend of elevated cancer risk with increasing DiMeIQx intake was observed in quintile analysis (P(trend) = 0.024). A higher intake of dietary mutagens (those in the two top quintiles) was associated with a 2-fold increased risk of pancreatic cancer among those without a family history of cancer but not among those with a family history of cancer. A possible synergistic effect of dietary mutagen exposure and smoking was observed among individuals with the highest level of exposure (top 10%) to PhIP and BaP, P(interaction) = 0.09 and 0.099, respectively. These data support the hypothesis that dietary mutagen exposure alone and in interaction with other factors contribute to the development of pancreatic cancer.

  18. Identification of mutagenic transformation products generated during oxidation of 3-methyl-4-nitrophenol solutions by orbitrap tandem mass spectrometry and quantitative structure-activity relationship analyses.

    PubMed

    Matsushita, Taku; Honda, Shiho; Kuriyama, Taisuke; Fujita, Yuki; Kondo, Takashi; Matsui, Yoshihiko; Shirasaki, Nobutaka; Takanashi, Hirokazu; Kameya, Takashi

    2018-02-01

    We used Ames assays to investigate the effects of ozonation (designated O 3 ), ozonation followed by chlorination (O 3 /Cl), an advanced oxidation process (AOP, UV/H 2 O 2 ), and AOP followed by chlorination (AOP/Cl) on the mutagenicity of solutions of 3-methyl-4-nitrophenol (3M4NP), a major environmental degradation product of the organophosphorus insecticide fenitrothion. Whereas O 3 did not induce mutagenicity, O 3 /Cl, AOP, and AOP/Cl converted 3M4NP into mutagenic transformation products (TPs). Using liquid chromatography-mass spectrometry, we detected a total of 138 peaks in the solutions subjected to O 3 /Cl, AOP, and AOP/Cl. To elucidate the TPs responsible for the observed mutagenicity, we performed simple regression analyses of the relationship between the area of each peak and the observed mutagenicity of samples withdrawn periodically during each oxidation process. The area of each of 10 peaks was found to be positively correlated (r 2  ≥ 0.8) with the observed mutagenicity, suggesting that the TPs corresponding to these peaks contributed to the mutagenicity. After taking into account the consistency of mutagenicity induction by the oxidation processes and analyzing the peaks by tandem mass spectrometry, we identified 3 TPs, corresponding to 6 peaks, as candidate mutagens. These TPs were assessed by means of 4 quantitative structure-activity relationship (QSAR) models, and all 3 were predicted to be mutagenic by at least one model. This result was consistent with our assumption that these TPs were mutagens. Ames assays of an authentic sample of one of the 3 TPs revealed that it did not contribute to the mutagenicity. This left 3-methoxy-4-nitrophenol and 2-[(E)-[(2,5-dihydroxyphenyl) methylidene]amino]-5-dihydroxybenzaldehyde on the list of mutagens suspected of contributing to the mutagenicity induced by AOP. No TPs were identified as candidate mutagens responsible for the mutagenicity induced by O 3 /Cl and AOP/Cl. Copyright © 2017 Elsevier Ltd

  19. Paving asphalt products exhibit a lack of carcinogenic and mutagenic activity.

    PubMed

    Goyak, Katy O; McKee, Richard H; Minsavage, Gary D; McGowan, Claude; Daughtrey, Wayne C; Freeman, James J

    2011-10-01

    A paving asphalt and a vacuum residuum (derived from crude oil by atmospheric and subsequent vacuum distillation and used as a blend stock for asphalt) were tested in skin carcinogenesis assays in mice and in optimized Ames assays for mutagenic activity. In the skin cancer tests, each substance was applied twice weekly for 104 weeks to the clipped backs of groups of 50 male C3H mice. Neither the paving asphalt nor the vacuum residuum (30% weight/volume and 75% weight/weight in US Pharmacopeia mineral oil, respectively) produced any tumors. The positive control benzo[a]pyrene (0.05% w/v in toluene) induced tumors in 46 of 50 mice, demonstrating the effectiveness of the test method. Salmonella typhimurium tester strain TA98 was used in the optimized Ames assay to evaluate mutagenic potential. Dimethylsulfoxide (DMSO) extractions of the substances were not mutagenic when tested up to toxic limits. Thus, under the conditions of these studies, neither the paving asphalt nor the vacuum residuum was carcinogenic or mutagenic.

  20. Potential of goat probiotic to bind mutagens.

    PubMed

    Apás, Ana Lidia; González, Silvia Nelina; Arena, Mario Eduardo

    2014-08-01

    The mutagen binding ability of the goat probiotics (Lactobacillus reuteri DDL 19, Lactobacillus alimentarius DDL 48, Enterococcus faecium DDE 39, and Bifidobacterium bifidum DDBA) was evaluated. The oral administration of these probiotics reduced fecal mutagens and intestinal cancer markers in goats. Secondly, the effects of probiotics against the mutagenesis induced by sodium azide (SA), and Benzopyrene (B[α]P) by performing the modified Ames test using Salmonella typhimurium TA 100 was investigated. The capacity to bind benzopyrene and the stability of the bacterial-mutagen complex was analyzed by HPLC. The dismutagenic potential against both mutagens was proportional to probiotic concentration. Results showed that probiotic antimutagenic capacity against SA was ranging from 13 to 78%. The mixture of four goat probiotics (MGP) displayed higher antimutagenic activity against SA than any individual strains at the same cell concentration. This study shows that the highest diminution of mutagenicity in presence of B[α]P (74%) was observed in presence of MGP. The antimutagenic activity of nearly all the individual probiotic and the MGP were in concordance with the B[α]P binding determined by HPLC. According to our results, the B[α]P binding to probiotic was irreversible still after being washed with DMSO solution. The stability of the toxic compounds-bacterial cell binding is a key consideration when probiotic antimutagenic property is evaluated. MGP exhibits the ability to bind and detoxify potent mutagens, and this property can be useful in supplemented foods for goats since it can lead to the removal of potent mutagens and protect and enhance ruminal health and hence food safety of consumers. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. An investigation of interurban variations in the chemical composition and mutagenic activity of airborne particulate organic matter using an integrated chemical class/bioassay system

    NASA Astrophysics Data System (ADS)

    Butler, J. P.; Kneip, T. J.; Daisey, J. M.

    Previous investigations in this laboratory have demonstrated that the mutagenic activities of extractable particulate organic matter (EOM) from cities which differ in their principal fuels and meteorology can vary significantly. To gain a better understanding of these interurban variations, an Integrated Chemical Class/Biological Screening System was developed and used for a more detailed examination of differences in the chemical composition and mutagenic activity of EOM. The screening system involved coupling in situ Ames mutagenicity determinations on high performance thin layer chromatography (HPTLC) plates with class specific chemical analyses on a second set of plates. The system was used to screen for mutagenic activity and selected chemical classes (including PAH, nitro-PAH, phenols, carboxylic acids, carbonyls, aza-arenes and alkylating agents) in EOM from the following sites: New York City; Elizabeth, N.J.; Mexico City; Beijing, China; Philadelphia, PA; and the Caldecott Tunnel (CA). The results of this study demonstrated mutagenic activity and chemical compositional differences in HPTLC subfractions of particulate organic matter from these cities and from the Caldecott Tunnel. The greatest interurban differences in chemical classes were observed for the phenols, carbonyl compounds and alkylating agents. Interurban variations in mutagenic activities were greatest for EOM subfractions of intermediate polarity. These differences are probably related to interurban differences in the fuels used, types of sources and atmospheric conditions. The relationships between these variables are not well understood at present.

  2. Assessment of Cellular Mutagenicity of Americano Coffees from Popular Coffee Chains.

    PubMed

    Liu, Zhen-Shu; Chen, Po-Wen; Wang, Jung-Yu; Kuo, Tai-Chen

    2017-09-01

    Coffee is a popular beverage worldwide, but coffee beans can be contaminated with carcinogens. The Ames Salmonella mutagenicity test is often used for analysis of carcinogens for mutagenicity. However, previous studies have provided controversial data about the direct mutagenicity of coffee beans based on Ames test results. This study was conducted to determine the mutagenicity of popular Americano coffee based on results from the Ames test. Coffee samples without additives that were served by five international coffee chain restaurants were subjected to the analysis using Salmonella Typhimurium tester strains TA98, TA100, and TA1535. The levels of bacterial revertants in samples from coffee chains were lower than the twofold criterion of the control sets, and no significant dose-response effect was observed with or without rat liver enzyme activation. These data indicate that Americano coffees from the selected coffee chains possessed no direct mutagenic activity with or without enzyme activation. These findings suggest a low mutagenic risk from Americano coffees served by the selected coffee chains and support the use of other methods to confirm the nonmutagenicity of coffee products. These results are consistent with most recent epidemiological reports.

  3. The photo-oxidation of automobile emissions: measurements of the transformation products and their mutagenic activity

    NASA Astrophysics Data System (ADS)

    Kleindienst, Tadeusz E.; Smith, David F.; Hudgens, Edward E.; Snow, Richard F.; Perry, Erica; Claxton, Larry D.; Bufalini, Joseph J.; Black, Francis M.; Cupitt, Larry T.

    Dilute mixtures of automobile emissions (comprising 50% exhaust and 50% surrogate evaporative emissions) were irradiated in a 22.7 m 3 smog chamber and tested for mutagenic activity by using a variant of the Ames test. The exhaust was taken from a single vehicle, a 1977 Ford Mustang equipped with a catalytic converter. Irradiated and nonirradiated gas-phase emissions were used in exposures of the bacteria, Salmonella typhimurium, strains TA100 and TA98. A single set of vehicular operating conditions was used to perform multiple exposures. The mutagenic activities of extracts from the particulate phase were also measured with the standard plate incorporation assay. (In most experiments only direct-acting mutagenic compounds were measured.) The gas-phase data for TA100 and TA98 showed increased activity for the irradiated emissions when compared to the nonirradiated mixture, which exhibited negligible activity with respect to the control values. The particulate phase for both the irradiated and nonirradiated mixtures showed negligible activity when results were compared to the control values for both strains. However, the experimental conditions limited the amount of extractable mass which could be collected in the particulate phase. The measured activities from the gas phase and particulate phase were converted to the number of revertants per cubic meter of effluent (i.e. the mutagenic density) to compare the contributions of each of these phases to the total mutagenic activity for each strain. Under the experimental conditions of this study, the mutagenic density of the gas-phase component of the irradiated mixture contributed approximately two orders of magnitude more of the total TA100 activity than did the particulate phase. For TA98 the gas-phase component contributed approximately one order of magnitude more. However, caution must be exercised in extrapolating these results to urban atmospheres heavily impacted by automotive emissions, because the bacterial

  4. Mutagenic screening of diamine monomers

    NASA Technical Reports Server (NTRS)

    Ross, W. D.; Noble, J. E.; Gridley, J. A.; Fullenkamp, J. M.; Wininger, M. T.; Graham, J. A.

    1983-01-01

    The effects of phenyl ring coupling moieties, of isomeric amine positions relative to the coupling groups, and of insertion of other coupling groups on the mutagenic response of a series of dianilines were investigated using the Ames Salmonella assay. Generally, S-9 metabolic activation from Aroclor-induced rat liver was required for mutagenic expression. The range of mutagenicity of steric isomers of several dianiline series was also investigated. No mutagenicity was found for purified samples of o,o' and m,p' isomers of methylene dianiline (MDA) and diaminobenzophenone, while varying degrees of mutagenicity were found for other isomers. The mutagenicity of "benzylogs" of MDA decreased as the degree of linear separation of the m,m' anilino groups by aromatic rings increased. Methylation and two-year storage increased mutagenic response in certain isomers of MDA. However, high performance liquid chromatography indicated there was no discernible change in m,p'-MDA samples aged under varied conditions over four months. Likewise, no change in mutagenicity was found.

  5. Volatilization of mutagens from beef during cooking.

    PubMed

    Rappaport, S M; McCartney, M C; Wei, E T

    1979-12-01

    The process of cooking beef substances which are mutagenic in the Ames Salmonella/microsome bioassay [1,2]. In this study, the formation and disposition of basic mutagens produced by cooking beef at different temperatures were examined. Mutagenic activity increased exponentially with cooking temperature between 137 degrees C and 252 degrees C. However, the amount of mutagenic activity remaining in the meat was only 1--7% of that which was volatilized into the air. The ingested dose of mutagens may therefore be significantly influenced by factors which restrict the dissipation of mutagens from the container, as well as by cooking temperature. Inhalation of airborne mutagens from cooking, as an alternative route of exposure, should be investigated when considered in light of some epidemiological data showing an excess of lung and bladder cancer among cooks and kitchen workers.

  6. Antioxidant, mutagenic and antimutagenic activities of an aqueous extract of Limoniastrum guyonianum gall.

    PubMed

    Krifa, Mounira; Bouhlel, Ines; Skandrani, Ines; Chekir-Ghedira, Leila; Ghedira, Kamel

    2014-01-01

    An aqueous extract of Limoniastrum guyonianum gall (G extract) was tested on Salmonella typhimurium to assess its mutagenic and antimutagenic effects. This extract showed no mutagenicity when tested with S. typhimurium strain TA104 either with or without exogenous metabolic activation mixture (S9), whereas our findings revealed that the aqueous gall extract induced a mutagenic effect in S. typhimurium TA1538 when tested in the presence, as well as in the absence, of S9 activation mixture at the concentration of 500 µg/mL. Thus, the same concentration produced a mutagenic effect, when incubated with S. typhimurium TA100 in the presence of metabolic activation mixture. In contrast, our results showed a weak antimutagenic potential of the same extract against sodium azide in the presence of S. typhimurium TA100 and S. typhimurium TA1538 without metabolic activation (S9), whereas, in the presence of S. typhimurium TA104, we obtained a significant inhibition percentage (76.39%) toward 3.25 µg/plate of methylmethanesulfonate. Antimutagenicity against aflatoxin B1, 4-nitro-o-phenylene-diamine and 2-aminoanthracène was significant, with an inhibition percentage of, respectively, 70.63, 99.3 and 63.37% in the presence of, respectively, S. typhimurium TA100, S. typhimurium TA1538 and S. typhimurium TA104 strains at a concentration of 250 µg/plate after metabolic activation (S9). Antioxidant capacity of the tested extract was evaluated using the enzymatic (xanthine/xanthine oxidase assay) and the nonenzymatic (2,2-diphenyl-1-picrylhydrazyl) system. G extract exhibited high antioxidant activity.

  7. Exposure to mutagenic chemicals in foundry and urban environments.

    PubMed

    Barański, B; Palus, J; Janik-Spiechowicz, E

    1989-01-01

    The study was aimed at the estimation of occupational exposure to mutagenic substances in a piston-ring foundry. The following samples were examined: solid phase of aerosol from the foundry and from different places of urban environment together with the foundry workers' urine collected during the 8-hour shift. The mutagenic substances were extracted from the collected material with acetone or concentrated with XAD-2 resin. The mutagenic property was estimated with the Ames' test using S. typhimurium strain TA98 without and with S9 fraction. The highest mutagenic activity was found at the following work-posts: caster, moulder, steerer of an induction furnace, and smelter and in the office rooms and in the flat occupied by heavy smokers. The mutagenic activity of aerosol at some other productive workposts in the foundry was similar to the mutagenic activity of aerosol in the office and flat rooms occupied by nonsmokers or in the street in Lodz. The mutagenic activity of urine from foundry workers was not correlated with the level of the occupational inhalation exposure to the mutagenic substances, however, the mutagenic activity of urine from smoking workers was about 10-20 times higher than from nonsmokers.

  8. STRUCTURE-ACTIVITY RELATIONSHIPS (SARS) AMONG MUTAGENS AND CARCINOGENS: A REVIEW

    EPA Science Inventory

    The review is an introduction to methods for evaluating structure-activity relationships (SARs), and, in particular, to those methods that have been applied to study mutagenicity and carcinogenicity. A brief history and some background material on the earliest attempts to correla...

  9. Factors influencing the mutagenic activity of the colon carcinogen 1,2-dimethylhydrazine in Salmonella typhimurium strain TA 1535 in vitro.

    PubMed

    Kerklaan, P R; Bouter, S; Mohn, G R

    1984-04-01

    The colon carcinogen 1,2-dimethylhydrazine (SMDH), a non-mutagen in the standard Ames assay, has been shown in previous experiments to become weakly mutagenic in Salmonella TA 1535 in vitro, when specific test conditions were used. The present studies were performed to determine more precisely the nature of metabolic factors and experimental conditions for optimal mutagenesis of SDMH in the same strain of Salmonella. First, it was confirmed that both the presence of rat liver S9 fractions (25 microliters/ml incubation mixture) and prolonged pre-incubation periods in liquid medium of at least 120 min were necessary to elicit SDMH mutagenesis. In contrast to results obtained with dimethylnitrosamine, which served as a model compound for the activation through oxidative, cytochrome P-450- and NADPH-dependent enzymatic processes, the activation of SDMH to mutagenic factors was not dependent on the presence of NADPH: in fact, NADPH strongly reduced the SDMH-induced mutation yields. It was also observed that growth of the indicator bacteria is an important prerequisite for mutation induction by SDMH. Aminoacetonitrile and disulfiram, two inhibitors of SDMH metabolism and carcinogenicity in mammals, also strongly inhibited SDMH mutagenesis in the present in vitro assay. It can, therefore, be concluded that (i) the right test protocol is of crucial importance for the detection of SDMH as a bacterial mutagen, and (ii) that activation pathways in vitro are (partially) different from presumed in vivo metabolism and activation.

  10. Identification of formaldehyde as the metabolite responsible for the mutagenicity of methyl tertiary-butyl ether in the activated mouse lymphoma assay.

    PubMed

    Mackerer, C R; Angelosanto, F A; Blackburn, G R; Schreiner, C A

    1996-09-01

    Methyl tertiary-butyl ether (MTBE), which is added to gasoline as an octane enhancer and to reduce automotive emissions, has been evaluated in numerous toxicological tests, including those for genotoxicity. MTBE did not show any mutagenic potential in the Ames bacterial assay or any clastogenicity in cytogenetic tests. However, it has been shown to be mutagenic in an in vitro gene mutation assay using mouse lymphoma cells when tested in the presence, but not in the absence, of a rat liver-derived metabolic activation system (S-9). In the present study, MTBE was tested to determine if formaldehyde, in the presence of the S-9, was responsible for the observed mutagenicity. A modification of the mouse lymphoma assay was employed which permits determination of whether a suspect material is mutagenic because it contains or is metabolized to formaldehyde. In the modified assay, the enzyme formaldehyde dehydrogenase (FDH) and its co-factor, NAD+ are added in large excess during the exposure period so that any formaldehyde produced in the system is rapidly converted to formic acid which is not genotoxic. An MTBE dose-responsive increase in the frequency of mutants and in cytotoxicity occurred without FDH present, and this effect was greatly reduced in the presence of FDH NAD+. The findings clearly demonstrate that formaldehyde derived from MTBE is responsible for mutagenicity of MTBE in the activated mouse lymphoma assay. Furthermore, the results suggest that the lack of mutagenicity/clastogenicity seen with MTBE in other in vitro assays might have resulted from inadequacies in the test systems employed for those assays.

  11. Urinary excretion of mutagens in coke oven workers.

    PubMed

    Clonfero, E; Granella, M; Marchioro, M; Barra, E L; Nardini, B; Ferri, G; Foà, V

    1995-03-01

    The influence of occupational exposure to polycyclic aromatic hydrocarbons (PAHs) on urinary mutagenic activity was assessed in 75 coke oven workers, using a highly sensitive bacterial mutagen technique (extraction with C18 resin and liquid micro-preincubation test on strain TA98 of Salmonella typhimurium in the presence of metabolizing and deconjugating enzymes). Exposure to PAHs was assessed according to the urinary excretion of 1-pyrenol; the main confounding factors were checked by the number of cigarettes smoked per day and the levels of nicotine and its metabolites in urine, or by ascertaining whether recommended dietary restrictions had been followed. Of the 20 urine samples which turned out to be positive (producing at least double the number of spontaneous revertants), 19 (95%) belonged to smokers. Only one non-smoker had obvious urinary mutagenic activity, and was highly exposed occupationally to PAHs (urinary 1-pyrenol of 3.930 mumol/mol of creatinine). Of the five urine samples from subjects who had not followed the recommended diet, two (40%) were clearly mutagenic. Multiple regression analysis (n = 67) showed that the presence of samples positive for urinary mutagenic activity depended only on smoking habits, if this confounding factor was assessed according to the number of cigarettes smoked per day, while the significant influence of exposure to PAH could be shown when the confounding factor was objectively estimated according to the urinary levels of nicotine and its metabolites. Assessment of the mutagenic potency of urinary extracts (net revertants/mmol creatinine) confirmed the strong influence of smoking habits on urinary mutagenic activity (all smokers 2156 +/- 2691 versus non-smokers 939 +/- 947 net revertants/mmol creatinine; Mann-Whitney test: P < 0.01). In smokers highly exposed to PAHs, greater excretion of mutagens with respect to low-exposure smokers was revealed (3548 +/- 4009 versus 1552 +/- 1227 net revertants/mmol creatinine; Mann

  12. Mutagenic activity associated with by-products of drinking water disinfection by chlorine, chlorine dioxide, ozone and UV-irradiation.

    PubMed Central

    Zoeteman, B C; Hrubec, J; de Greef, E; Kool, H J

    1982-01-01

    A retrospective epidemiological study in The Netherlands showed a statistical association between chlorination by-products in drinking water and cancer of the esophagus and stomach for males. A pilot-plant study with alternative disinfectants was carried out with stored water of the Rivers Rhine and Meuse. It was demonstrated that the increase of direct acting mutagens after treatment with chlorine dioxide is similar to the effect of chlorination. Ozonation of Rhine water reduced the mutagenic activity for Salmonella typhimurium TA 98 both with and without metabolic activation. UV alone hardly affects the mutagenicity of the stored river water for S. typh. TA 98. In all studies, practically no mutagenic activity for S. typh. TA 100 was found. Although remarkable changes in the concentration of individual organic compounds are reported, the identity of the mutagens detected is yet unclear. Compounds of possible interest due to their removal by ozonation are 1,3,3-trimethyloxindole, dicyclopentadiene and several alkylquinolines. Compounds which might be responsible for the increased mutagenicity after chlorination are two brominated acetonitriles and tri(2-chlorethyl) phosphate. Furthermore, the concentration procedure with adsorption on XAD resin and the subsequent elution step may have affected the results. It is proposed to focus further research more on the less volatile by-products of disinfection than on the trihalomethanes. PMID:7151762

  13. Assessment of the mutagenic potential of cyanobacterial extracts and pure cyanotoxins.

    PubMed

    Sieroslawska, Anna

    2013-11-01

    The aim of the study was to assess the mutagenic potential of extracts obtained from the cyanobacterial bloom-forming cells harvested from the water body located in Lubelszczyzna region of southeastern Poland. Three cyanotoxins, microcystin-LR, cylindrospermopsin and anatoxin-a were detected in some of the studied samples in different concentrations. All extracts were assessed for their potential mutagenic effects with the use of a short-term bacterial assay, the Ames test. Mutagenic activity was observed in four of all ten studied extracts, mainly toward the Salmonella typhimurium TA100 strain. On the contrary, the cyanotoxins in purified forms occurred not to be mutagenic or cytotoxic towards S. typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2 uvrA and WP2 [pKM101] up to a concentration of 10 μg/ml. Similarly, there were no effects after bacteria exposure to the mixture of purified toxins. It has been also detected that after fractionation, genotoxic impact of previously mutagenic extracts was weaker and the highest potency in revertant induction possessed fractions containing very hydrophilic compounds. The results indicate, that while tested cyanotoxins were not directly responsible for the observed mutagenicity of the extracts analysed, some synergistic interactions with other unidentified cyanobacterial-derived factors involved in the process are possible. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Mutagenicity of burnt gun propellants

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Felton, J.S.; Lewis, P.; Knize, M.G.

    1989-08-02

    The use of the Ames/Salmonella assay as a workplace monitoring method is a long-standing practice at LLNL. This practice has led to the discovery of very mutagenic soot in and around a 4 inch test gun. To the authors' knowledge this is the first finding of mutagenic components in the residue from gun propellants, although there have been numerous reports of mutagenic compounds associated with high explosives -- compounds of entirely different chemical composition (Won et al., 1976). In addition, Ase et al., 1985, analyzed the propellant combustion products of both a M16 rifle and a 105 mm caliber gunmore » with HPLC and GC/MS methods, and found a number of PAHs with known toxicological effects. No biological analysis was done on the residues. Further investigation in our laboratory found that direct acting mutagens where produced upon open burning of the propellants. Small gauge firearms when tested also showed mutagenic residue. Preliminary efforts to identify the mutagenic components estimate that 2-3 compounds are responsible for the biological activity. The identity of these compounds is under investigation. 8 refs., 4 tabs.« less

  15. Mutagenicity of heated sugar-casein systems: effect of the Maillard reaction.

    PubMed

    Brands, C M; Alink, G M; van Boekel, M A; Jongen, W M

    2000-06-01

    The formation of mutagens after the heating of sugar-casein model systems at 120 degrees C was examined by the Ames test, using Salmonella typhimurium strain TA100. Several sugars (glucose, fructose, galactose, tagatose, lactose, and lactulose) were compared in their mutagenicities. Mutagenicity could be fully ascribed to Maillard reaction products and strongly varied with the kind of sugar. The differences in mutagenicity among the sugar-casein systems were caused by a difference in reaction rate and a difference in reaction mechanism. Sugars with a comparable reaction mechanism (glucose and galactose) showed a higher mutagenic activity corresponding with a higher Maillard reactivity. Disaccharides showed no mutagenic activity (lactose) or a lower mutagenic activity (lactulose) than their corresponding monosaccharides. Ketose sugars (fructose and tagatose) showed a remarkably higher mutagenicity compared with their aldose isomers (glucose and galactose), which was due to a difference in reaction mechanism.

  16. Past, present, and future of mutagens in cooked foods.

    PubMed

    Sugimura, T

    1986-08-01

    Mutation assay with Salmonella typhimurium enabled us to detect various types of mutagens in cooked foods. A series of mutagenic heterocyclic amines has been isolated and identified in broiled fish and meat and in pyrolyzates of amino acids and proteins. Feeding experiments showed these mutagens to be carcinogenic in mice and rats. The mechanism of formation and pathway of metabolic activation of these heterocyclic amines have been elucidated. Their contents in various cooked foods have been determined. The presence of mutagenic nitropyrenes (some of which were confirmed as carcinogens) in grilled chicken was also established. Roasted coffee beans also yield mutagens such as methylglyoxal. The formation of mutagen precursors, including beta-carboline derivatives and tyramine which become mutagens with nitrite treatment, was found during food processing. Oncogene activation in animal tumors induced by some of these food mutagens/carcinogens has been confirmed. The role of mutagens/carcinogens in cooked foods in human cancer development has not yet been exactly evaluated. In order to do this, more information on their carcinogenic potency, human intake, metabolism in the human body, and the effects of combined administration with other initiators, promoters and other modifying factors in food is required.

  17. Organic emissions from coal pyrolysis: mutagenic effects.

    PubMed Central

    Braun, A G; Wornat, M J; Mitra, A; Sarofim, A F

    1987-01-01

    Four different types of coal have been pyrolyzed in a laminar flow, drop tube furnace in order to establish a relationship between polycyclic aromatic compound (PAC) evolution and mutagenicity. Temperatures of 900K to 1700K and particle residence times up to 0.3 sec were chosen to best simulate conditions of rapid rate pyrolysis in pulverized (44-53 microns) coal combustion. The specific mutagenic activity (i.e., the activity per unit sample weight) of extracts from particulates and volatiles captured on XAD-2 resin varied with coal type according to the order: subbituminous greater than high volatile bituminous greater than lignite greater than anthracite. Total mutagenic activity (the activity per gram of coal pyrolyzed), however, varied with coal type according to the order: high volatile bituminous much greater than subbituminous = lignite much greater than anthracite, due primarily to high organic yield during high volatile bituminous coal pyrolysis. Specific mutagenic activity peaked in a temperature range of 1300K to 1500K and generally appeared at higher temperatures and longer residence times than peak PAC production. PMID:3311724

  18. Mutagenicity, anticancer activity and blood brain barrier: similarity and dissimilarity of molecular alerts.

    PubMed

    Toropov, Andrey A; Toropova, Alla P; Benfenati, Emilio; Salmona, Mario

    2018-06-01

    The aim of the present work is an attempt to define computable measure of similarity between different endpoints. The similarity of structural alerts of different biochemical endpoints can be used to solve tasks of medicinal chemistry. Optimal descriptors are a tool to build up models for different endpoints. The optimal descriptor is calculated with simplified molecular input-line entry system (SMILES). A group of elements (single symbol or pair of symbols) can represent any SMILES. Each element of SMILES can be represented by so-called correlation weight i.e. coefficient that should be used to calculate descriptor. Numerical data on the correlation weights are calculated by the Monte Carlo method, i.e. by optimization procedure, which gives maximal correlation coefficient between the optimal descriptor and endpoint for the training set. Statistically stable correlation weights observed in several runs of the optimization can be examined as structural alerts, which are promoters of the increase or the decrease of a biochemical activity of a substance. Having data on several runs of the optimization correlation weights, one can extract list of promoters of increase and list of promoters of decrease for an endpoint. The study of similarity and dissimilarity of the above lists has been carried out for the following pairs of endpoints: (i) mutagenicity and anticancer activity; (ii) mutagenicity and blood brain barrier; and (iii) blood brain barrier and anticancer activity. The computational experiment confirms that similarity and dissimilarity for pairs of endpoints can be measured.

  19. Changes in mutagenicity of protein pyrolyzates by reaction with nitrite.

    PubMed

    Yoshida, D; Matsumoto, T

    1978-09-01

    Pyrolyzates of protein and related materials were treated with nitrite under acidic conditions, and the mutagenic activity toward Salmonella tester strains was determined. After treatment with nitrite in acidic solution, casein pyrolyzate, an extract of roasted chicken meat, tobacco-smoke condensate and some aromatic amines showed appreciable decreases in their mutagenic activities toward Salmonella typhimurium TA 98. Aromatic amines in the pyrolyzates may be changed by nitrite treatment to other forms having no or lower mutagenic activity toward Salmonella typhimurium TA 98. The contribution by aromatic amines to the total mutagenic activity of the pyrolyzates was as high as 80% in both casein pyrolyzate and extract of roasted chicken meat and 50% in tobacco-smoke condensate. Pyrolyzates of protein and related materials did not show a decrease in the mutagenic activity toward Salmonella typhimurium TA 100 with the same treatment.

  20. Chemistry of mutagens and carcinogens in broiled food.

    PubMed Central

    Nishimura, S

    1986-01-01

    From a chemical point of view, the following subjects are important areas in studies on mutagens and carcinogens in broiled foods. In addition to heterocyclic amines which need microsomal activation, the structural elucidation of more labile direct-acting mutagens is necessary. It is known that there are still various unknown minor mutagens in broiled foods. Although the structural characterization of such compounds is more difficult, it is important since they might be hazardous in spite of their low mutagenicity. A more feasible and easier method for quantitative analysis of mutagens, in addition to HPLC and GC/MS methods presently employed, must be developed. The mechanism of formation of mutagens by broiling of food should be studied. An effective chemical method to prevent formation of mutagens or to destroy them, once formed, should be developed. PMID:3757944

  1. Analysis of commercial bouillons for trace levels of mutagens.

    PubMed

    Stavric, B; Matula, T I; Klassen, R; Downie, R H

    1993-12-01

    A new method, developed specifically for the extraction of heterocyclic aromatic amine (HAA) type mutagens from different food matrices, was applied to various forms of commercially available bouillons. This procedure is based on liquid-liquid extraction of the sample at different pH values. Recovery and reproducibility of the procedure was determined by processing spiked samples using a mutagenicity bioassay technique as an endpoint. The mutagenicity was tested in the Salmonella/microsome assay using strain TA98 with metabolic activation. 22 bouillon samples in liquid, cube or powder forms from seven manufacturers were extracted and tested for potential mutagenicity. The mutagenic activity of these samples varied and ranged from non-detectable to about 1200 induced revertants per gram of solid material, with a median value of approximately 250 revertants/g. The mutagenic response appeared to be dependent on the source rather than the type or form of the product tested. A negative response was obtained from only one chicken bouillon, and the highest positive response was obtained from a beef bouillon in cube form. It appears that the average beef sample, regardless of form, has a higher mutagenic potency than chicken or chicken and turkey samples. Overall, the intake of mutagens from commercial bouillons (obtained as cubes, concentrates or dry mixes) to prepare one serving (as bouillon, soup, casseroles, etc.) is considerably less than that reported in the literature for one serving of fried beef or pork. The extractability and mutagenic characteristics of these samples indicate the presence of HAA-type mutagens. Work is in progress to identify the mutagenic factors in bouillons.

  2. Mutagenic substances in pyrolysate obtained by burning polyvinylchloride-product at 1000 degrees C.

    PubMed

    Yonezawa, Y; Saigusa, S; Takahagi, M; Nishioka, H

    1999-06-25

    In order to detect possible mutagenic substances in pyrolysate obtained by burning polyvinyl chloride product (PVC-P) at approximately 1000 degrees C, mutagenicity of rough extracts obtained by extraction with various solvents for the products was investigated by means of reversion mutation assay using Salmonella typhimurium TA98 and TA100 with or without microsomal metabolic activation (S9 mix). Strong mutagenicity in TA98 without S9 mix was observed in acetone-extract of PVC-P. The extract was fractionated into acidic, neutral and basic by liquid-liquid distribution and the mutagenicity in TA98 without S9 mix was found in the neutral fraction. Identification of mutagenic substances in the neutral fraction from acetone extract, which showed the strongest mutagenicity, was attempted by means of thin layer chromatography and capillary gas chromatography. The results suggest that mutagenic substances from pyrolysate of PVC-P are benzanthrone and an isomer of benzo(c)cinnoline. The results also suggest that burning wastes containing plastic products is not always safe even if at 1000 degrees C and further research on the problem is necessary. Copyright 1999 Elsevier Science B.V.

  3. Effect of pentachlorophenol on the activation of 2,6-dinitrotoluene to genotoxic urinary metabolites in CD-1 mice: A comparison of G1 enzyme activities and urine mutagenicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    George, S.E.; Chadwick, R.W.; Creason, J.P.

    1991-01-01

    2,6-Dinitrotoluene (2,6-DNT) and pentachlorophenol (PCP) are used for industrial purposes and are found in the environment as hazardous contaminants. Because concurrent exposure to both compounds can occur, it is of interest to determine if organochlorine compounds potentiate the effect of nitroaromatic chemicals. A significant increase in mutagenicity was observed in urines from mice treated with 2,6-DNT alone and in combination with PCP. By week 4, mice that received both 2,6-DNT and PCP excreted urine that was more mutagenic than that from animals which received only 2,6-DNT. At weeks 2 and 4, mice were sacrificed and intestinal enzyme activities (nitroreductase, azomore » reductase, {beta}-glucuronidase, dechlorinase, and dehydrochlorinase) were quantitated. The enhanced genotoxicity observed in urines from 2,6-DNT/PCP-treated mice coincided with a decrease in nitroreductase and an increase in {beta}-glucuronidase activities in the small intestine.« less

  4. [The hygienic evaluation of the mutagenic potential of industrial wastes].

    PubMed

    Zhurkov, V S; Rusakov, N V; Tonkopiĭ, N I; Sycheva, L P; Akhal'tseva, L V; Neiaskina, E V; Pirtakhiia, N V; Malysheva, A G; Rastiannikov, E G

    1998-01-01

    A combination of two approaches to assessing the carcinogenic and mutagenic potentials of industrial waste is proposed. One approach includes determination of the carcinogenic and mutagenic properties of individual chemicals of waste, the other involves biological indication of the cumulative mutagenic activity of waste samples. The mutagenic potential of some waste samples of aircraft industry was determined.

  5. Mutagenicity of airborne particulates in the rubber industry.

    PubMed

    Barański, B; Indulski, J; Janik-Spiechowicz, E; Palus, J

    1989-12-01

    The aim of this work was to evaluate the mutagenic activity of airborne particulate matter in the rubber industry. Air was sucked through Whatman glass-fibre filters with Staplex pumps and adsorbed substances and fume particles were extracted with acetone or toluene for 2 h in a ultrasonic cleaner. After separation of the insoluble solid phase by filtration, solvent was evaporated at a temperature of 70 degrees C in an argon atmosphere. The residue was stored at -20 degrees C. Mutagenicity was determined by the Salmonella plate incorporation assay with the tester strain TA98 and activity is related either to the weight of aerosol (rev mg-1) or to the volume of atmospheric sample (rev m-3). The fumes emitted from the tyre tread line, calender feeding, and tyre vulcanizing processes, showed the highest mutagenic activity (55-211 rev mg-1, + S9). At these and at other workplaces (extruder mill, carbon black station, mixer loading), mutagenic activity related to the volume of air was in the range of 22-158 rev m-3, + S9. The results indicate the need to reduce and monitor mutagenic contamination in order to increase the safety of work in the rubber industry.

  6. Mutagenicity and human chromosomal effect of stevioside, a sweetener from Stevia rebaudiana Bertoni.

    PubMed Central

    Suttajit, M; Vinitketkaumnuen, U; Meevatee, U; Buddhasukh, D

    1993-01-01

    Leaves of Stevia rebaudiana Bertoni have been popularly used as a sweetener in foods and beverages for diabetics and obese people due to their potent sweetener stevioside. In this report, stevioside and steviol were tested for mutagenicity in Salmonella typhimurium strains TA98 and TA100 and for chromosomal effects on cultured human lymphocytes. Stevioside was not mutagenic at concentrations up to 25 mg/plate, but showed direct mutagenicity to only TA98 at 50 mg/plate. However, steviol did not exhibit mutagenicity in either TA98 or TA100, with or without metabolic activation. No significant chromosomal effect of stevioside and steviol was observed in cultured blood lymphocytes from healthy donors (n = 5). This study indicates that stevioside and steviol are neither mutagenic nor clastogenic in vitro at the limited doses; however, in vivo genotoxic tests and long-term effects of stevioside and steviol are yet to be investigated. PMID:8143647

  7. Hair dyes are mutagenic: identification of a variety of mutagenic ingredients.

    PubMed Central

    Ames, B N; Kammen, H O; Yamasaki, E

    1975-01-01

    We have previously described a sensitive bacterial test for dectecting carcinogens as mutagens. We have previously described a sensitive bacterial test for detecting carcinogens as mutagens. We show here that 89% (150/169) of commercial oxidative-type (hydrogen peroxide) hair dye formulations are mutagenic in this test. Of the 18 components of these hair dyes, nine show various degrees of mutagenicity:2,4-diaminoanisole, 4-nitro-o-phenylenediamine, 2-nitro-p-phenylenediamine, 2,5-diaminoanisole, 2-amino-5-nitrophenol, m-phenylenediamine, o-phenylenediamine, 2-amino-4-nitrophenol, and 2,5-diaminotoluene. Three hair dye components (p-phenylenediamine, 2,5-diaminotuluene, and 2,5-diaminoanisole) become strongly mutagenic after oxidation by H2O2: the mutagenic product of p-phenylenediamine is identified as the known trimer, Bandrowski's base. 2,4-Diaminotoluene, a hair dye component until recently, is also shown to be mutagenic: this compound has been shown to be a carcinogen in rats and is used in large amounts in the polyurethane foam industry. About 20,000,000 people (mostly women) dye their hair in the U.S. and the hazard could be considerable if these chemicals are actually mutagenic and carcinogenic in humans. Images PMID:1094469

  8. Mutagenicity and genotoxicity studies of aspartame.

    PubMed

    Otabe, Akira; Ohta, Fumio; Takumi, Asuka; Lynch, Barry

    2018-02-08

    Two studies were conducted to further assess its mutagenic and genotoxic potential. In a bacterial reverse mutation pre-incubation study, Salmonella typhimurium strains TA100, TA1535, TA98, and TA1537 and Escherichia coli WP2 uvrA were treated with aspartame at concentrations of up to 5000 μg/plate with or without metabolic activation and showed no mutagenic potential. Similarly, in vivo micronucleus testing of aspartame following gavage administration (500-2000 mg/kg body weight) to Crlj:CD1(ICR) strain SPF male mice showed no increase in the proportion of micronucleated polychromatic erythrocytes in bone marrow cells collected and evaluated 24 or 48 h post administration. Overall, aspartame had no potential for mutagenic or genotoxic activity. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miguel, A.G.; Daisey, J.M.; Sousa, J.A.

    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-prophagemore » 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.« less

  10. A comparison of methods for concentrating mutagens in drinking water--recovery aspects and their implications for the chemical character of major unidentified mutagens.

    PubMed

    Wigilius, B; Borén, H; Carlberg, G E; Grimvall, A; Möller, M

    1985-12-01

    A comparison of techniques for concentrating mutagenic compounds in drinking water has shown that XAD-2 adsorption and dichloromethane extraction have acceptable and almost identical enrichment properties, while purging at an elevated temperature is inappropriate in this context. Quantitatively, the most important drinking water mutagens could only be adsorbed (extracted) after acidification of the water, and even then recovery was far from complete. Recovery experiments with known mutagens from pulp mill effluents have shown that none of the major chlorination-stage mutagens identified thus far can explain the mutagenic activity of extracts from neutral or acidified chlorinated drinking water.

  11. Mutagenicity assessment of airborne particles in Mexico City

    NASA Astrophysics Data System (ADS)

    Villalobos-Pietrini, Rafael; Blanco, Salvador; Gomez-Arroyo, Sandra

    The Ames's TA98 strain of Salmonella typhimurium with and without mammalian metabolic activation was used to detect the mutagenic activity of organic chemicals associated with airborne particles. Two kinds of particles: total suspended (TSP) and those particles with an aerodynamic diameter of 10 μm or smaller (PM 10) were collected in glass fiber filters using high-volume samplers during the dry season (December 1989-March 1990) in the Metropolitan Area of Mexico City at five stations of the air quality network belonging to the Ministry of Social Development. Although the highest mass concentrations of particles were obtained from the Northeastern and Southeastern areas, the largest frequency of mutations was found Downtown which indicated that vehicle exhaust was an important source. Contrary to what was expected, the mutagenic responses were higher for PM10 than for TSP samples. On the other hand, the microsome activation increased significantly the mutagenic activity of the complex mixture, which hinted at the presence of higher amounts of indirect (or promutagens) than direct mutagens both for TSP and PM10.

  12. A level change in mutagenicity of Japanese tap water over the past 12 yr.

    PubMed

    Takanashi, Hirokazu; Kishida, Misako; Nakajima, Tsunenori; Ohki, Akira; Akiba, Michihiro

    2011-05-01

    A relative comparison study of mutagenicity in Japanese tap water was conducted for 1993 and 2005 surveys. It intended to assess the effects of advanced water treatment installations to water works, improvement of raw water quality and improvement of residual HOCl concentration controlling. Sampling points (taps) were the same in both surveys. The results of 245 samples obtained by the Ames Salmonella mutagenicity test (Ames test) were analyzed. The Ames tests were conducted by using Salmonella typhimurium TA98 and TA100 strains with and without exogenous activation (S9). With the exception of TA100-S9, the other conditions needed no discussion as a factor in the mutagenicity level change. The average mutagenicity in 1993 and 2005 under the conditions of TA100-S9 were 2600 and 1100 net revertantL(-1), respectively. This indicated that the mutagenicity level of Japanese tap water decreased during the 12-yr period. Particularly a remarkable decrease in mutagenicity was observed in the water works where the advanced water treatments were installed during the 12-yr period. The advanced water treatments were effective in decreasing the mutagenicity of tap water. Mutagenicity also decreased in the water works with conventional water treatments; the improvement of residual HOCl concentration controlling was also considered to be effective in decreasing the mutagenicity of tap water. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Anti-proliferative and mutagenic activities of aqueous and methanol extracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae).

    PubMed

    Er, Hui Meng; Cheng, En-Hsiang; Radhakrishnan, Ammu Kutty

    2007-09-25

    The anti-proliferative effects of the aqueous and methanol extracts of leaves of Pereskia bleo (Kunth) DC (Cactaceae) against a mouse mammary cancer cell line (4T1) and a normal mouse fibroblast cell line (NIH/3T3) were evaluated under an optimal (in culture medium containing 10% foetal bovine serum (FBS)) and a sub-optimal (in culture medium containing 0.5% FBS) conditions. Under the optimal condition, the aqueous extract showed a significant (p<0.05) anti-proliferative effect at 200 microg/mL and 300 microg/mL in 4T1 cells and 300 microg/mL in NIH/3T3 cells, whereas the methanol extract did not show any notable anti-proliferative effect in these cell lines, at any of the concentrations tested. Under the sub-optimal condition, the aqueous extract showed a significant (p<0.05) anti-proliferative effect at 200 microg/mL and 300 microg/mL in NIH/3T3 cells, whilst the methanol extract showed a significant (p<0.05) anti-proliferative effect at 200 microg/mL and 300 microg/mL in both cell lines. An upward trend of apoptosis was observed in both 4T1 and NIH/3T3 cells treated with increasing concentrations of the aqueous extract. The level of apoptosis observed at all the concentrations of the aqueous extract tested was consistently higher than necrosis. There was a significant (p<0.05) increase in the level of necrosis observed in the 4T1 cells treated with 300 microg/mL of the methanol extract. Generally, the level of necrosis was noted to be higher than that of apoptosis in the methanol extract-treated cells. The mutagenicity assay performed showed that in the absence of S-9 liver metabolic activation, the extract was not mutagenic up to the concentration of 165 microg/mL . However, in the presence of S-9 liver metabolic activation, the aqueous extract was mutagenic at all the concentrations tested. This study shows that both the aqueous and methanol extracts of the leaves from Pereskia bleo (Kunth) DC (Cactaceae) do not have appreciable anti-proliferative effect on

  14. Ames Test to Detect Mutagenicity of 2-Alkylcyclobutanones: A Review.

    PubMed

    Barbezan, Angélica B; Martins, Regiane; Bueno, Jennifer B; Villavicencio, Anna Lúcia C H

    2017-07-01

    Food irradiation is an effective and safe method for preservation and long-term storage, and it is approved for use in over 60 countries for various applications in a wide variety of food products. This process is performed by use of accelerated electron beams, X-rays, or gamma radiation ( 60 Co or 137 Cs). 2-Alkylcyclobutanones (2-ACBs) are the only known radiolytic products generated from foods that have fatty acids (triglycerides) and are subjected to irradiation. Since the 1990s toxicological safety studies of 2-ACBs have been conducted extensively through synthetic compounds, then and tests to determine if the compounds have any mutagenic activity are strictly necessary. The Ames test was chosen by many researchers to assess the mutagenicity of 2-ACBs. The test uses distinct bacterial cell lines Salmonella typhimurium to detect point mutations at sites guanine-cytosine (G-C) and Escherichia coli to detect point mutations at sites adenine-thymine (A-T). This bibliographic research aims to bring together all the results obtained and a comparison and cell lines used, type of plates, and solvents. This research showed that no mutagenic activity was observed in any of the cell lines and concentrations evaluated by the works of authors, so the 2-ACBs compounds showed no mutagenic substance in concentrations detectable by the Ames test. © 2017 Institute of Food Technologists®.

  15. Mutagens in cooked foods - metabolism and genetic toxicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Felton, J.S.; Bjeldanes, L.F.; Hatch, F.T.

    1984-02-17

    Recently developed in our laboratories is an efficient extraction procedure incorporating XAD resin adsorption which yields from 200/sup 0/C grilled ground beef an extract containing 230 Salmonella TA1538 revertants per g fresh weight of original ground beef. These mutagenic components are specific for frameshift-sensitive Salmonella strains and have an absolute requirement for metabolic activation. Normal-phase HPLC separation of methanol-extractable metabolites generated from reaction of 2-amino-3-methylimidazo (4,5-f)quinoline (IQ), a mutagenic component of broiled food with rat liver microsomes resulted in one direct-acting mutagenic peak and a second more polar peak still requiring metabolic activation. Two potent thermally-produced bacterial mutagens, 3-amino-1-methyl-5H-pyrido (4,3-b)more » indole (Trp-P-2) and IQ, were examined in mammalian cells. In excision repair-deficient CHO cells, Trp-P-2 exposure caused cytotoxicity, mutagenicity, sister chromatid exchange, and chromosomal aberrations at concentrations more than 30-fold lower than those for IQ. In normal repair-proficient CHO cells Trp-P-2 was one-half as active and IQ was inactive. Relative to Trp-P-2, IQ is much more potent in the Salmonella bacterial system than in mammalian CHO cells.« less

  16. Evaluation of acute and subacute toxicity and mutagenic activity of the aqueous extract of pecan shells [Carya illinoinensis (Wangenh.) K. Koch].

    PubMed

    Porto, Luiz Carlos Santos; da Silva, Juliana; Ferraz, Alexandre de Barros Falcão; Corrêa, Dione Silva; dos Santos, Marcela Silva; Porto, Caroline Dalla Lana; Picada, Jaqueline Nascimento

    2013-09-01

    The infusion of pecan shells has been used to prevent and control hypercholesterolemia, diabetes and toxicological diseases. The aim of the present study was to evaluate toxicity and mutagenic effects of pecan shells aqueous extract (PSAE). Wistar rats were treated with a single dose of 300 or 2000 mg/kg of PSAE in the acute toxicity test. For the subacute test, the animals received 10 or 100 mg/kg of PSAE for 28 days. The mutagenicity was evaluated using Salmonella/microsome assay in TA1535, TA1537, TA98, TA100 and TA102 S. typhimurium strains in the presence and absence of metabolic activation (S9 mix) and micronucleus test in bone marrow. HPLC analyses indicated the presence of tannins, flavonoids, gallic and ellagic acids. Except for triglycerides, all treated groups presented normal hematological and biochemical parameters. Lower levels of triglycerides and weight loss were observed in the 100 mg/kg group. Mutagenic activities were not detected in S. typhimurium strains and by the micronucleus test. Based on these results, PSAE was not able to induce chromosomal or point mutations, under the conditions tested. The 100mg/kg dose showed significant antihyperlipidemic action, with no severe toxic effects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. The mouse lymphoma thymidine kinase assay for the assessment and comparison of the mutagenic activity of cigarette mainstream smoke particulate phase.

    PubMed

    Schramke, H; Meisgen, T J; Tewes, F J; Gomm, W; Roemer, E

    2006-10-29

    The mouse lymphoma thymidine kinase assay (MLA) has been optimized to quantitatively determine the in vitro mutagenicity of cigarette mainstream smoke particulate phase. To test whether the MLA is able to discriminate between different cigarette types, specially constructed cigarettes each containing a single tobacco type - Bright, Burley, or Oriental - were investigated. The mutagenic activity of the Burley cigarette was statistically significantly lower, up to approximately 40%, than that of the Bright and Oriental cigarettes. To determine the impact of two different sets of smoking conditions, American-blend cigarettes were smoked under US Federal Trade Commission/International Organisation for Standardisation conditions and under Massachusetts Department of Public Health (MDPH) conditions. Conventional cigarettes - eight from the US commercial market plus the Reference Cigarettes 1R4F and 2R4F - and an electrically heated cigarette smoking system (EHCSS) prototype were tested. There were no statistically significant differences between the two sets of smoking conditions on a per mg total particulate matter basis, although there was a consistent trend towards slightly lower mutagenic activity under MDPH conditions. The mutagenic activity of the EHCSS prototype was distinctly lower than that of the conventional cigarettes under both sets of smoking conditions. These results show that the MLA can be used to assess and compare the mutagenic activity of cigarette mainstream smoke particulate phase in the comprehensive toxicological assessment of cigarette smoke.

  18. Mutagenicity of chalks. A case in which the test results led to the improvement of the quality of commercial goods.

    PubMed

    Hayatsu, H; Ohara, Y; Hayatsu, T; Togawa, K

    1983-10-01

    Mutagenicity testing, of methanolic extracts of chalks, by the Salmonella/mammalian-microsome system revealed that the blue and the green chalks contained mutagens. A positive mutagenic response was observed on Salmonella typhimurium strain TA98, both in the presence and absence of the microsome system (S9). The source of the mutagenicity was traced to the blue pigment used for manufacturing these chalks. The pigment, copper phthalocyanine, a product of a Japanese chemical industrial company, was found to contain impurities that were mutagenic. The mutagenic principle giving positive response in the TA98 in the presence of S9 was purified 10(5)-fold from the original pigment. Although its structure is yet to be elucidated, this indirect frame-shift mutagen had a strong activity: 5700 His+ revertants per microgram. This information, delivered in the beginning of 1981, prompted the manufacturer to start supplying a mutagen-free product. As a result, the blue chalks on the market became no longer mutagenic in the summer of 1982.

  19. Exploratory monitoring of air pollutants for mutagenicity activity with the Tradescantia stamen hair system.

    PubMed

    Schairer, L A; Van't Hof, J; Hayes, C G; Burton, R M; de Serres, F J

    1978-12-01

    The Tradescantia genetic system developed by the late Dr. Arnold H. Sparrow for the study of effects of ionizing radiation is applicable to chemical mutagen detection. Early radiobiological data demonstrated that the stamen hairs were sensitive to as little as 0.25 rad of x-rays and that the number of cells showing a phenotypic change in pigmentation from blue to pink plateaus after approximately 21 days of chronic, low-level irradiation. Exposures to the air pollutants SO(2), NO(2), and O(3) and to vapors of mutagens such as 1,2-dibromoethane (DBE) and ethyl methanesulfonate (EMS) demonstrated the usefulness of the system as a detector of chemical mutagens. A significant number of phenotypic changes was observed following exposures to as little as 0.14 ppm of DBE. The maximum sensitivity of the system is obtained with long-term or chronic exposures because the response increases linearly in proportion to the duration of exposure up to 21 days. To monitor industrial sites for atmospheric mutagens a mobile laboratory was designed to support plant culture in the field. Environment-controlled growth chambers were installed in a trailer so that both ambient air fumigations and concurrent clean-air control exposures could be made. Sites monitored by the mobile laboratory were: Elizabeth, N. J.; Charleston, W. Va.; Birmingham, Ala.; Baton Rouge, La.; Houston, Tex.; Upland, Calif.; Magna, Utah; and Grand Canyon, Ariz. The latter site at Grand Canyon served as a clean air control study. Atmospheric contaminants from petroleum and chemical processing plants generated a significant number of phenotypic pigment changes that were 17 to 31% above the control levels; contaminants from steel and copper smelters, automotive combustion products and photochemical compounds were negative. Chemical analyses are underway to identify the atmospheric mutagens at the sites that showed a positive response.

  20. Mutagenicity of biodiesel or diesel exhaust particles and the effect of engine operating conditions.

    PubMed

    Kisin, Elena R; Shi, X C; Keane, Michael J; Bugarski, Aleksandar B; Shvedova, Anna A

    2013-03-01

    Changing the fuel supply from petroleum based ultra-low sulfur diesel (ULSD) to biodiesel and its blends is considered by many to be a viable option for controlling exposures to particulate material (PM). This is critical in the mining industry where approximately 28,000 underground miners are potentially exposed to relatively high concentrations of diesel particulate matter (DPM). This study was conducted to investigate the mutagenic potential of diesel engine emissions (DEE) from neat (B100) and blended (B50) soy-based fatty acid methyl ester (FAME) biodiesel in comparison with ULSD PM using different engine operating conditions and exhaust aftertreatment configurations. The DPM samples were collected for engine equipped with either a standard muffler or a combination of the muffler and diesel oxidation catalytic converter (DOC) that was operated at four different steady-state modes. Bacterial gene mutation activity of DPM was tested on the organic solvent extracts using the Ames Salmonella assay. The results indicate that mutagenic activity of DPM was strongly affected by fuels, engine operating conditions, and exhaust aftertreatment systems. The mutagenicity was increased with the fraction of biodiesel in the fuel. While the mutagenic activity was observed in B50 and B100 samples collected from both light-and heavy-load operating conditions, the ULSD samples were mutagenic only at light-load conditions. The presence of DOC in the exhaust system resulted in the decreased mutagenicity when engine was fueled with B100 and B50 and operated at light-load conditions. This was not the case when engine was fueled with ULSD. Heavy-load operating condition in the presence of DOC resulted in a decrease of mutagenicity only when engine was fueled with B50, but not B100 or ULSD. Therefore, the results indicate that DPM from neat or blended biodiesel has a higher mutagenic potency than that one of ULSD. Further research is needed to investigate the health effect of biodiesel

  1. Mutagenicity of biodiesel or diesel exhaust particles and the effect of engine operating conditions

    PubMed Central

    Kisin, Elena R; Shi, X.C; Keane, Michael J; Bugarski, Aleksandar B; Shvedova, Anna A

    2015-01-01

    Background Changing the fuel supply from petroleum based ultra-low sulfur diesel (ULSD) to biodiesel and its blends is considered by many to be a viable option for controlling exposures to particulate material (PM). This is critical in the mining industry where approximately 28,000 underground miners are potentially exposed to relatively high concentrations of diesel particulate matter (DPM). This study was conducted to investigate the mutagenic potential of diesel engine emissions (DEE) from neat (B100) and blended (B50) soy-based fatty acid methyl ester (FAME) biodiesel in comparison with ULSD PM using different engine operating conditions and exhaust aftertreatment configurations. Methods The DPM samples were collected for engine equipped with either a standard muffler or a combination of the muffler and diesel oxidation catalytic converter (DOC) that was operated at four different steady-state modes. Bacterial gene mutation activity of DPM was tested on the organic solvent extracts using the Ames Salmonella assay. Results The results indicate that mutagenic activity of DPM was strongly affected by fuels, engine operating conditions, and exhaust aftertreatment systems. The mutagenicity was increased with the fraction of biodiesel in the fuel. While the mutagenic activity was observed in B50 and B100 samples collected from both light-and heavy-load operating conditions, the ULSD samples were mutagenic only at light-load conditions. The presence of DOC in the exhaust system resulted in the decreased mutagenicity when engine was fueled with B100 and B50 and operated at light-load conditions. This was not the case when engine was fueled with ULSD. Heavy-load operating condition in the presence of DOC resulted in a decrease of mutagenicity only when engine was fueled with B50, but not B100 or ULSD. Conclusions Therefore, the results indicate that DPM from neat or blended biodiesel has a higher mutagenic potency than that one of ULSD. Further research is needed to

  2. Structure-Activity Relationship Models for Rat Carcinogenesis and Assessing the Role Mutagens Play in Model Predictivity

    PubMed Central

    Carrasquer, C. Alex; Batey, Kaylind; Qamar, Shahid; Cunningham, Albert R.; Cunningham, Suzanne L.

    2016-01-01

    We previously demonstrated that fragment based cat-SAR carcinogenesis models consisting solely of mutagenic or non-mutagenic carcinogens varied greatly in terms of their predictive accuracy. This led us to investigate how well the rat cancer cat-SAR model predicted mutagens and non-mutagens in their learning set. Four rat cancer cat-SAR models were developed: Complete Rat, Transgender Rat, Male Rat, and Female Rat, with leave-one-out (LOO) validation concordance values of 69%, 74%, 67%, and 73%, respectively. The mutagenic carcinogens produced concordance values in the range of 69–76% as compared to only 47–53% for non-mutagenic carcinogens. As a surrogate for mutagenicity comparisons between single site and multiple site carcinogen SAR models was analyzed. The LOO concordance values for models consisting of 1-site, 2-site, and 4+-site carcinogens were 66%, 71%, and 79%, respectively. As expected, the proportion of mutagens to non-mutagens also increased, rising from 54% for 1-site to 80% for 4+-site carcinogens. This study demonstrates that mutagenic chemicals, in both SAR learning sets and test sets, are influential in assessing model accuracy. This suggests that SAR models for carcinogens may require a two-step process in which mutagenicity is first determined before carcinogenicity can be accurately predicted. PMID:24697549

  3. QSAR modeling for predicting mutagenic toxicity of diverse chemicals for regulatory purposes.

    PubMed

    Basant, Nikita; Gupta, Shikha

    2017-06-01

    The safety assessment process of chemicals requires information on their mutagenic potential. The experimental determination of mutagenicity of a large number of chemicals is tedious and time and cost intensive, thus compelling for alternative methods. We have established local and global QSAR models for discriminating low and high mutagenic compounds and predicting their mutagenic activity in a quantitative manner in Salmonella typhimurium (TA) bacterial strains (TA98 and TA100). The decision treeboost (DTB)-based classification QSAR models discriminated among two categories with accuracies of >96% and the regression QSAR models precisely predicted the mutagenic activity of diverse chemicals yielding high correlations (R 2 ) between the experimental and model-predicted values in the respective training (>0.96) and test (>0.94) sets. The test set root mean squared error (RMSE) and mean absolute error (MAE) values emphasized the usefulness of the developed models for predicting new compounds. Relevant structural features of diverse chemicals that were responsible and influence the mutagenic activity were identified. The applicability domains of the developed models were defined. The developed models can be used as tools for screening new chemicals for their mutagenicity assessment for regulatory purpose.

  4. Mutagenicity of basic fractions derived from lamb and beef cooked by common household methods.

    PubMed

    Barrington, P J; Baker, R S; Truswell, A S; Bonin, A M; Ryan, A J; Paulin, A P

    1990-03-01

    Mutagen production was examined in lamb and beef in relation to certain common household cooking methods. Mutagenicity was assessed, after extraction of the basic fraction of cooked meat samples, using Salmonella typhimurium strain TA1538 with added rat-liver S-9 homogenate. Little or no mutagenicity was found in barbecued lamb chops, in microwave-cooked lamb chops, sirloin steak, leg of lamb, or rolled beef loaf, in roasted leg of lamb or rolled beef loaf, in stewed blade steak or in boiled chuck steak. However, the basic fraction from well-done, edible fried or grilled meat contained mutagenic activity equivalent to approximately 30,000 TA1538 revertants/100 g cooked meat. It was found tht the mutagenic activity of grilled lamb chops, sirloin and rump steaks was directly related to the average surface temperatures attained during cooking. Use of butter as a frying medium was particularly associated with higher mutagenicity in meat samples. Fried meats (rump and fillet steaks) generally yielded higher mutagenic activity than did grilled meats (rump steak, lamb chops) at comparable temperatures of the cooking medium. Using similar cooking procedures, lamb did not differ markedly from beef in mutagenic activity.

  5. Mutagenicity of adsorbates to a copper-phthalocyanine derivative recovered from municipal river water.

    PubMed

    Sayato, Y; Nakamuro, K; Ueno, H; Goto, R

    1990-12-01

    Blue cotton, bearing a covalently bound copper-phthalocyanine derivative capable of adsorbing polycyclic aromatic hydrocarbons (PAHs) over 3 rings, was applied to recover mutagens from the Katsura River which is a tributary of the Yodo River. The Ames Salmonella/microsome assay with TA98 and TA100 of the blue cotton concentrate recovered from the river water demonstrated indirect mutagenicity toward TA98. The subfractions separated by Sephadex G-25 gel chromatography also showed direct mutagenicity in strains YG1021 and YG1024, the nitroreductase- and O-acetyltransferase-overproducing derivatives of TA98; this activity was greatly increased by the addition of S9 mix, especially in YG1024. However, these subfractions were less mutagenic with TA98NR or TA98/1,8-DNP6, regardless of whether S9 mix was present or not. The behaviors of these mutagenic activities therefore suggested that frameshift mutagens of both directly mutagenic nitroarenes and indirectly mutagenic aminoarenes were present in the blue cotton concentrate from the river water.

  6. Mutagenicity of arsenic in mammalian cells: role of reactive oxygen species

    NASA Technical Reports Server (NTRS)

    Hei, T. K.; Liu, S. X.; Waldren, C.

    1998-01-01

    Arsenite, the trivalent form of arsenic present in the environment, is a known human carcinogen that lacked mutagenic activity in bacterial and standard mammalian cell mutation assays. We show herein that when evaluated in an assay (AL cell assay), in which both intragenic and multilocus mutations are detectable, that arsenite is in fact a strong dose-dependent mutagen and that it induces mostly large deletion mutations. Cotreatment of cells with the oxygen radical scavenger dimethyl sulfoxide significantly reduces the mutagenicity of arsenite. Thus, the carcinogenicity of arsenite can be explained at least in part by it being a mutagen that depends on reactive oxygen species for its activity.

  7. URINARY MUTAGENICITY: A BIOMARKER OF GENOTOXIC EXPOSURES VIA AIR, WATER, AND DIET

    EPA Science Inventory

    During the past 30 years, ~100 studies have evaluated human urine for mutagenic activity using the Salmonella (Ames) mutagenicity assay. Urinary mutagenicity has been shown to correlate well with other biomarkers, including DNA and hemoglobin adducts, urinary metabolites, and chr...

  8. Sperm shape abnormality and urine mutagenicity in mice treated with niclosamide.

    PubMed

    Vega, S G; Guzmán, P; García, L; Espinosa, J; Cortinas de Nava, C

    1988-02-01

    Niclosamide, a widely used anthelmintic drug in underdeveloped countries, is known to be mutagenic in the Salmonella typhimurium microsomal test system. The urine obtained from mice treated with niclosamide is mutagenic in the TA98 and TA1538 strains. Its effects on mouse-sperm morphology were evaluated in CD1 and (BALB/cJ x DBA/2J) F1 mice after 5 daily oral niclosamide doses of either 60, 80, 100 or 120 mg/kg. A statistically significant increase in abnormal sperm morphology was detected in both CD1 and (BALB/cJ x DBA/2J) F1 mice. No drug-related effects on testis weight nor on sperm count were observed in either genotype. Urine samples obtained from niclosamide-treated F1 mice were assayed with the Salmonella typhimurium strain TA1538 both in the absence and presence of beta-glucuronidase. In the absence of glucuronidase, urine mutagenicity increased with increasing dose and the highest doses were toxic. In the presence of glucuronidase, urine mutagenicity and toxicity also increased. Only at the highest dose (120 mg/kg), however, was there a positive correlation between the urine mutagenic activity and an increase in the number of abnormal sperm. The results of this study suggest that the increase in abnormal sperm depends on the systemic presence of non-conjugated niclosamide metabolites.

  9. URINARY MUTAGENICITY AS A BIOMARKER OF COOKED-MEAT-ASSOCIATED MUTAGENS AND RISK FOR COLORECTAL ADENOMA

    EPA Science Inventory

    Urinary Mutagenicity as a Biomarker of Cooked-Meat-Associated Mutagens and Risk for Colorectal Adenoma

    In a controlled feeding study involving 60 subjects, we have investigated urinary mutagenicity as a biomarker of exposure to cooked-meat-associated mutagens. In a separa...

  10. Mutagenicity of particulate emissions from the M16 rifle: variation with particle size.

    PubMed

    Palmer, W G; Andrews, A W; Mellini, D; Terra, J A; Hoffmann, F J; Hoke, S H

    1994-08-01

    Emissions generated by firing the M16 rifle with the propellant WC844 in a combustion chamber designed to simulate conditions of actual use were tested for mutagenic activity in the Salmonella/Ames assay. Dimethyl sulfoxide extracts of emissions collected from either the breech or muzzle end of the rifle were mutagenic in three strains of Salmonella (TA1537, TA1538, and TA98) both in the presence and absence of metabolic activation systems (S9). The extracts were negative in strains TA100 and TA102. Aerosols generated by firing the M16 rifle were fractionated according to aerodynamic diameter. Submicrometer particles were far more mutagenic than particles with aerodynamic diameters between 1 and 15 microns. The mutagens associated with the smaller particles were more active in the presence of S9, while extracts of larger particles were as active, or more active, in the absence of S9. Heavier particles, which settled rapidly out of the airstream, were not mutagenic.

  11. Chemical fate and changes in mutagenic activity of antibiotics nitrofurazone and furazolidone during aqueous chlorination.

    PubMed

    Nakamura, Hitomi; Kawakami, Tsuyoshi; Niino, Tatsuhiro; Takahashi, Yasuo; Onodera, Sukeo

    2008-12-01

    Reactions of nitrofuran antibiotics (nitrofurazone (NFZ) and frazolidone (FZD)) with hypochlorite in aqueous solution were investigated under the conditions that simulate wastewater disinfection. The chlorination byproducts were determined by high performance liquid chromatography. At the levels of 5 microM, NFZ reacted rapidly with free chlorine in neutral pH (7.0), while the FZD-hypochlorite reaction was reasonably slow under the same pH. Nevertheless, the strong mutagenic parents disappeared completely after the hypochlorite reactions, and the chlorination byproducts were observed to exert a weak mutagenic effect on Salmonella typhimurium TA100 without S9-mix. The extent of the reactions depended on the chlorine dose, solution pH and compound structures.

  12. Evidence for the presence of mutagenic arylamines in human breast milk and DNA adducts in exfoliated breast ductal epithelial cells.

    PubMed

    Thompson, Patricia A; DeMarini, David M; Kadlubar, Fred F; McClure, Gail Y; Brooks, Lance R; Green, Bridgett L; Fares, Manal Y; Stone, Angie; Josephy, P David; Ambrosone, Christine B

    2002-01-01

    Aromatic and heterocyclic amines are ubiquitous environmental mutagens present in combustion emissions, fried meats, and tobacco smoke, and are suspect human mammary carcinogens. To determine the presence of arylamines in breast tissue and fluid, we examined exfoliated breast ductal epithelial cells for DNA adducts and matched human milk samples for mutagenicity. Breast milk was obtained from 50 women who were 4-6 weeks postpartum, and exfoliated epithelial-cell DNA was evaluated for bulky, nonpolar DNA adducts by (32)P-postlabeling and thin-layer chromatography. Milk was processed by acid hydrolysis, and the extracted organics were examined in the standard plate-incorporation Ames Salmonella assay using primarily strain YG1024, which detects frameshift mutations and overexpresses aryl amine N-acetyltransferase. DNA adducts were identified in 66% of the specimens, and bulky adducts migrated in a pattern similar to that of 4-aminobiphenyl standards. The distribution of adducts did not vary by NAT2 genotype status. Of whole milk samples, 88% (22/25) had mutagenic activity. Among the samples for which we had both DNA adduct and mutagenicity data, 58% (14/19) of the samples with adducts were also mutagenic, and 85% (11/13) of the mutagenic samples had adducts. Quantitatively, no correlation was observed between the levels of adducts and the levels of mutagenicity. Separation of the milk showed that mutagenic activity was found in 69% of skimmed milk samples but in only 29% of the corresponding milk fat samples, suggesting that the breast milk mutagens were moderately polar molecules. Chemical fractionation showed that mutagenic activity was found in 67% (4/6) of the basic fractions but in only 33% (2/6) of acidic samples, indicating that the mutagens were primarily basic compounds, such as arylamines. Although pilot in nature, this study corroborates previous findings of significant levels of DNA adducts in breast tissue and mutagenicity in human breast milk and

  13. Induction of Abasic Sites by the Drinking-Water Mutagen MX in Salmonella TA100

    EPA Science Inventory

    Mutagen X (MX) is a chlorinated furanone that accounts for more of the mutagenic activity of drinking water than any other disinfection by-product. It is one of the most potent base-substitution mutagens in the Salmonella (Ames) mutagenicity assay, producing primarily GC to TA mu...

  14. Evaluation of mutagenic and antimutagenic activities of oligorutin and oligoesculin.

    PubMed

    Ben Rhouma, Ghada; Chebil, Latifa; Krifa, Mounira; Ghoul, Mohamed; Chekir-Ghedira, Leila

    2012-12-01

    Rutin and esculin have been polymerised by laccase. Five fractions with M(w)¯ between 2127.42 and 8331.85g/mol for oligorutins, and between 688.12 and 6973g/mol for oligoesculins, were obtained. Fourier transformed infrared analysis showed that oligorutins were formed through C-C, C-O and CO linkages, while oligoesculins were obtained through C-C linkages. Monomers, their oligomers and their metabolites exhibited no mutagenic effect. Oligorutins and oligoesculins were more efficient in reducing the mutagenicity of methyl methanesulphonate, by, respectively, 69% and 64.8% in the presence of Salmonella typhimurium TA104, and 79.7% and 68.9% in the presence of S. typhimurium TA102, than were their monomers. The same oligomers revealed greater significant inhibitory effect of 2-aminoanthracene mutagenicity (respectively 82.4% and 79.3% in the presence of S. typhimurium TA104, and 89.2% and 82.9% in the presence of S. typhimurium TA102), than their monomers. Our results strongly suggest the enhancement of the tested monomer antimutagenicity after polymerisation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Mutagenicity of nitrogen compounds from synthetic crude oils: collection, separation and biological testing

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rao, T K; Epler, J L; Guerin, M R

    1980-01-01

    In order to determine the long range health effects such as carcinogenicity/mutagenicity/teratogenicity/toxicity, associated with the newly emerging energy technologies, we have utilized the Ames Salmonella assay to evaluate mutagenic properties of synthetic fuels. Coupling with class fractionation was necessary. Organic extraction and liquid/liquid partitioning was used to separate acidic and basic fraction. The neutral material was separated using Sephadex LH-20 gel filtration into saturated and aromatic fractions of various ring sizes. The alkaline fraction was subfractionated eluting with benzene and ethanol on a basic alumina column and then with isopropanol and acetone using a Sephadex LH-20 gel column. The frameshiftmore » strain TA-98 was utilized along with Aroclor-induced rat liver homogenate (S-9 mix) for the mutagenicity assay. The natural crude oils were slightly mutagenic, the polynucleararomatics constituting the activity, while the coal-derived fuels indicated mutagenicity associated with alkaline constituents as well as polyaromatics. Hydrotreated coal (H-coal, HDT) or Shale (Paraho-Shale oil, HDT) derived fuels were not mutagenic. Ninety percent of the mutagenic activity in alkaline fraction was recovered in the acetone subfraction. High resolution spectroscopy of this fraction indicates polycyclic aromatic primary amines along with azaarenes as organic constituents responsible for the mutagenic activity associated with shale- and coal-derived fuels.« less

  16. Evaluation of the cytotoxicity, genotoxicity, mutagenicity, and antimutagenicity of propolis from Tucuman, Argentina.

    PubMed

    Nieva Moreno, María I; Zampini, Iris C; Ordóñez, Roxana M; Jaime, Gloria S; Vattuone, Marta A; Isla, María I

    2005-11-16

    This study evaluates the toxic, genotoxic/mutagenic, and antimutagenic effects of propolis extract from Amaicha del Valle, Tucumán, Argentina. The cytotoxicity assays carried out with the lethality test of Artemia salina revealed that the LD50 was around 100 microg/mL. Propolis extracts showed no toxicity to Salmonella typhimurium TA98 and TA100 strains and Allium cepa at concentrations that have antibiotic and antioxidant activities. Otherwise, for the testing doses, neither genotoxicity nor mutagenicity was found in any sample. The propolis extracts were able to inhibit the mutagenesis of isoquinoline (IQ) and 4-nitro o-phenylenediamine (NPD) with ID50 values of 40 and 20 microg/plate, respectively. From this result, the studied propolis may be inferred to contain some chemical compounds capable of inhibiting the mutagenicity of direct-acting and indirect-acting mutagens. A compound isolated from Amaicha del Valle propolis, 2',4'-dihydroxychalcone, showed cytotoxic activity (LC50 values of 0.5 microg/mL) but was not genotoxic or mutagenic. Furthermore, this compound was able to inhibit the mutagenicity of IQ (ID50 values of 1 microg/plate) but was unable to inhibit the mutagenicity of NPD. Our results suggest a potential anticarcinogenic activity of Amaicha del Valle propolis and the chalcone isolated from it.

  17. Mutagenicity of fume particles from metal arc welding on stainless steel in the Salmonella/microsome test.

    PubMed

    Maxild, J; Andersen, M; Kiel, P

    1978-01-01

    Mutagenic activity of fume particles produced by metal arc welding on stainless steel (ss) is demonstrated by using the Salmonella/microsome mutagenicity test described by Ames et al., with strain TA100 (base-pair substitution) and TA98 (frame-shift reversion). Results of a representative but limited selection of processes and materials show that mutagenic activity is a function of process and process parameters. Welding on stainless steel produces particles that are mutagenic, whereas welding on mild steel (ms) produces particles that are not. Manual metal arc (MMA) welding on stainless steel produces particles of higher mutagenic activity than does metal inert gas (MIG) welding, and fume particles produced by MIG welding under short-arc transfer. Further studies of welding fumes (both particles and gases) must be performed to determine process parameters of significance for the mutagenic activity.

  18. Lipoamidase activity in normal and mutagenized pancreatic cholesterol esterase (bile salt-stimulated lipase).

    PubMed Central

    Hui, D Y; Hayakawa, K; Oizumi, J

    1993-01-01

    Purified human milk lipoamidase was digested with endoproteinase Lys-C and the digested peptides were subjected to gasphase microsequence analysis. The sequencing of three isolated peptides of human milk lipoamidase revealed the identity of this protein with human milk bile salt-stimulated lipase (pancreatic cholesterol esterase). The identity of the cholesterol esterase with lipoamidase was confirmed by expressing a recombinant form of rat pancreatic cholesterol esterase and testing for lipoamidase activity of the recombinant protein. The results showed that the recombinant cholesterol esterase displayed both lipolytic and lipoamidase activities and was capable of hydrolysing triacetin and lipoyl-4-aminobenzoate (LPAB). The mechanisms of the esterase and amidase activities of the enzyme were further tested by determining enzyme activity in a mutagenized cholesterol esterase with a His435-->Gln435 substitution. This mutation has been shown previously to abolish enzyme activity against esterase substrates [DiPersio, Fontaine and Hui (1991) J. Biol. Chem. 266, 4033-4036]. We showed that the mutagenized protein was effective in hydrolysing the amidase substrate LPAB and displayed similar enzyme kinetics to those of the native enzyme. These data indicate that the mechanism for the cholesterol esterase hydrolysis of lipoamides is different from that of the hydrolysis of substrates with an ester linkage. The presence of an enzyme in the gastrointestinal tract capable of both ester and amide hydrolysis suggests an important role for this protein in the digestion and absorption processes. PMID:8471055

  19. 40 Years of the Salmonella Mutagenicity Assay: Implications for 21st Century Toxicology

    EPA Science Inventory

    The Salmonella (Ames) mutagenicity assay was developed and introduced by Bruce Ames and colleagues in 1971. Since then, it has become the standard assay for hazard identification of mutagens worldwide. It is a first-tier test for mutagenic activity in the pharmaceutical and chemi...

  20. Activation of aminoimidazole carcinogens by nitrosation: mutagenicity and nucleotide adducts

    PubMed Central

    Zenser, Terry V.; Lakshmi, Vijaya M.; Schut, Herman A. J.; Zhou, Hui-jia; Josephy, P. David

    2009-01-01

    2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) are heterocyclic amines (HCA) derived from high temperature cooking of meat and thought to cause colon cancer in humans. Reactive nitrogen oxygen species, which are mediators of the inflammatory response, can convert these amines to the corresponding N-nitrosamines, N-NO-IQ and N-NO-MeIQx. This study was designed to evaluate whether these N-nitrosamines are genotoxic and could be responsible, in part, for the high incidence of colon cancer in individuals with colitis. Such an association would counsel reduced intake of well-done red meat by colitis patients. Mutagenicity was evaluated by reversion of a lacZ frameshift allele in three different E. coli strains. Strains DJ701 and DJ702 express recombinant (S. typhimurium) aromatic amine N-acetyltransferase; DJ702 also expresses recombinant human cytochrome P450 1A2 and NADPH-P450 reductase; and DJ2002 served as an N-acetyltransferase-negative control. In strain DJ701, N-NO-IQ and N-NO-MeIQx elicited dose-dependent mutagenicity, which was not further increased in DJ702. Neither nitrosamine was mutagenic in strain DJ2002. While both N-nitrosamines are stable for >4 hours (pH 7.4, 37°C), they react with DNA or 2′-deoxyguanosine 3′-monophosphate at lower pH (5.5) to form adducts. HOCl, a component of the inflammatory response, increased adduct formation, as measured by 32P-postlabeling. Following treatment with nuclease P1 and separation by two-dimensional thin-layer chromatography and then HPLC, N-NO-IQ and N-NO-MeIQx were shown to form the same adducts as those formed by N-OH-MeIQx or N-OH-IQ, namely N-(deoxyguanosin-8-yl) adducts. In summary, these N-nitrosamines are genotoxic and might be alternatives to their hydroxylamine analogues as activated intermediates leading to initiation of colon cancer in individuals with colitis. PMID:19449459

  1. Lack of mutagens in deep-fat-fried foods obtained at the retail level.

    PubMed

    Taylor, S L; Berg, C M; Shoptaugh, N H; Scott, V N

    1982-04-01

    The basic methylene chloride extract from 20 of 30 samples of foods fried in deep fat failed to elicit any mutagenic response that could be detected in the Salmonella typhimurium/mammalian microsome assay. The basic extracts of the remaining ten samples (all three chicken samples studied, two of the four potato-chip samples, one of four corn-chip samples, the sample of onion rings, two of six doughnuts, and one of three samples of french-fried potato) showed evidence of weak mutagenic activity. In these samples, amounts of the basic extract equivalent to 28.5-57 g of the original food sample were required to produce revertants at levels of 2.6-4.8 times the background level. Only two of the acidic methylene chloride extracts from the 30 samples exhibited mutagenic activity greater than 2.5 times the background reversion level, and in both cases (one corn-chip and one shrimp sample) the mutagenic response was quite weak. The basic extract of hamburgers fried in deep fat in a home-style fryer possessed higher levels of mutagenic activity (13 times the background reversion level). However, the mutagenic activity of deep-fried hamburgers is some four times lower than that of pan-fried hamburgers.

  2. Analysis of mutagenic activity of biohazardous organics in Kanawha River sediments. Technical completion report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    White, A.R.; Waldron, M.C.

    1988-01-01

    Residual chemical contamination of Kanawha River sediments may constitute a health hazard. Sediment cores have been analyzed using a coupled bioassay/chemical fractionation procedure. Both bacterial mutagenicity and sister chromatid exchange (SCE) analyses were conducted on sediment samples. Pocatalico River sediments extracts showed no response in either bacterial mutagenicity assay or SCE assay. Extracts from Armour Creek and the Kanawha River induced mutagenicities in the presence of S9 enzymes. The same extracts produced a significant increase in human chromosomal cross-over events.

  3. Potential of plant genetic systems for monitoring and screening mutagens

    PubMed Central

    Nilan, R. A.

    1978-01-01

    Plants have too long been ignored as useful screening and monitoring systems of environmental mutagens. However, there are about a dozen reliable, some even unique, plant genetic systems that can increase the scope and effectiveness of chemical and physical mutagen screening and monitoring procedures. Some of these should be included in the Tier II tests. Moreover, plants are the only systems now in use as monitors of genetic effects caused by polluted atmosphere and water and by pesticides. There are several major advantages of the plant test systems which relate to their reproductive nature, easy culture and growth habits that should be considered in mutagen screening and monitoring. In addition to these advantages, the major plant test systems exhibit numerous genetic and chromosome changes for determining the effects of mutagens. Some of these have not yet been detected in other nonmammalian and mammalian test systems, but probably occur in the human organism. Plants have played major roles in various aspects of mutagenesis research, primarily in mutagen screening (detection and verification of mutagenic activity), mutagen monitoring, and determining mutagen effects and mechanisms of mutagen action. They have played lesser roles in quantification of mutagenic activity and understanding the nature of induced mutations. Mutagen monitoring with plants, especially in situ on land or in water, will help determine potential genetic hazards of air and water pollutants and protect the genetic purity of crop plants and the purity of the food supply. The Tradescantia stamen-hair system is used in a mobile laboratory for determining the genetic effects of industrial and automobile pollution in a number of sites in the U.S.A. The fern is employed for monitoring genetic effects of water pollution in the Eastern states. The maize pollen system and certain weeds have monitored genetic effects of pesticides. Several other systems that have considerable value and should be

  4. Mutagenicity of particle emissions from solid fuel cookstoves: A literature review and research perspective.

    PubMed

    Shen, Guofeng

    2017-07-01

    Household solid fuel use is a major source of many air pollutants causing severe air pollution and adverse health outcomes. In evaluation of health impacts of household air pollution, it is essential to characterize toxic properties like mutagenicity of residential fuel combustion emissions and exposure assessments. Mutagenicity of emissions from solid fuel cookstoves were analyzed through a literature review. T98 and TA100 strains are two most widely used strains in mutagenic Ames test, and results for these two strains are generally positively correlated though they have different endpoints. Direct and indirect mutagenic activities are positively correlated, and statistically insignificantly different though indirect mutagenic emissions are apparently higher. Mutagenicity emission factors on the basis of fuel energy (MJ) or useful energy delivered (MJd) for solid fuel cookstoves vary in nearly 3 orders of magnitude, ranging from 3.0×10 4 rev./MJd to 1.8×10 7 rev./MJd (or 1.1×10 4 rev./MJ to 4.2×10 6 rev./MJ). Low mutagenic emissions are reported for high efficiency stoves such as a forced-draft one. Mutagenicity emission factors are positively correlated with emissions of PM 2.5 . Relationship between mutagenicity and polycyclic aromatic hydrocarbons (PAHs) emissions is inconsistent among studies as PAHs are minor fractions of toxic organics contributing to the total mutagenicity. Generally, studies on mutagenicity of emissions from household cookstoves are very limited, and future studies are encouraged on mutagenic emissions from different fuel types and household stoves, evaluation of mutagenic activities of both gaseous and particulate emissions, and toxicology and exposure assessments of household air pollution. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Evaluation of micronuclei induction capacity and mutagenicity of organochlorine and organophosphate pesticides.

    PubMed

    Yaduvanshi, Santosh K; Srivastava, Nalini; Marotta, Francesco; Jain, Shalini; Yadav, Hariom

    2012-09-01

    The genotoxic and mutagenic effects of two commonly used organochlorine pesticides, lindane (LND) and endosulfan (ENS), and two commonly used organophosphate pesticides, chlorpyrifos (CPF) and monocrotophos (MCP) were assessed using in vivo mouse bone marrow micronucleus test and in vitro Ames Salmonella/ microsome mutagenicity test. The results showed that these pesticides alone or in combination, induced significantly high frequency of micronuclei (MN) formation that increased with concentration of pesticides. All these four pesticides produced significant increase in the frequencies of micronucleated-polychromatic erythrocytes (MN-PCE) and decrease infrequencies of PCE in dose-dependent manner. The results indicate the suppression of proliferative activity of the bone marrow and increase in the extent of cell death. ENS and MCP showed mutagenic potential in Salmonella/ microsome assay. ENS induced mutagenic and nontoxic response only in TA98 tester strain of S.typhimurium at the dose of 500 μg/plate and in the absence of metabolic activation. MCP showed weak mutagenic and nontoxic effect only in TA100 tester strain at the dose of 5000 μg/plate in both assays, with or without metabolic activation when compared with negative control. MCP was toxic in TA98 tester strain at the dose of 5000 μg/plate in absence of metabolic activation while reduction in toxicity was seen on addition of S9 mixture. The study clearly showed the genotoxic potential of all these four pesticides and mutagenic response of endosulfan and monocrotophos.

  6. Exposure of pharmacy personnel to mutagenic antineoplastic drugs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nguyen, T.V.; Theiss, J.C.; Matney, T.S.

    1981-01-01

    The Salmonella reversion test was used to measure the mutagenic activities of urine concentrates from individuals preparing cancer chemotherapy agents for intravenous administration. Longitudinal studies were performed in which the total urine produced in 24 hour periods was collected, starting on a Sunday at 7:00 p.m. after a duty-free weekend and extending over an eight day period. There was no detectable increase in mutagenic activity in the urine concentrates of three pharmacy administrators who had no contact with these drugs. All six individuals admixing drugs in open-faced, horizontal laminar flow hoods displayed a two-fold increase in mutagenesis by the fourthmore » day with peak values of 2.7 to 24-fold occurring on days five and six, reduced values by day seven with a return to the spontaneous level by day eight. When four of the six positive individuals in the preceding experiment admixed comparable amounts of chemotherapeutic drugs in a closed-faced, vertical laminar flow hood, no increase in mutagenic activity was detected in their urine concentrates over the eight day period.« less

  7. Urine mutagenicity and biochemical effects of the drinking water mutagen, 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX), following repeated oral administration to mice and rats.

    PubMed

    Meier, J R; Monarca, S; Patterson, K S; Villarini, M; Daniel, F B; Moretti, M; Pasquini, R

    1996-06-17

    Mutagenicity analysis of urine from rats treated by oral gavage with MX at a dose of 64 mg/kg for 14 days revealed that only 0.3% of the administered compound was excreted in a genotoxically active form. At lower doses, mutagenicity was not detectable. No evidence of micronucleus induction in peripheral blood erythrocytes was observed in mice treated similarly. These findings indicate that MX is extensively detoxified in vivo and is unlikely to cause genetic damage in systemic tissues except at relatively high doses where detoxification pathways become saturated. In a separate experiment, significant depressions were observed in D-glucaric acid and thioether excretion and in levels of several liver enzymes involved in xenobiotic metabolism. The mechanism for these metabolic alterations and their relevance to the in vivo metabolism of the compound require further investigation.

  8. Development of fecal microbial enzyme mix for mutagenicity assay of natural products.

    PubMed

    Yeo, Hee Kyung; Hyun, Yang-Jin; Jang, Se-Eun; Han, Myung Joo; Lee, Yong Sup; Kim, Dong-Hyun

    2012-06-01

    Orally administered herbal glycosides are metabolized to their hydrophobic compounds by intestinal microflora in the intestine of animals and human, not liver enzymes, and absorbed from the intestine to the blood. Of these metabolites, some, such as quercetin and kaempherol, are mutagenic. The fecal bacterial enzyme fraction (fecalase) of human or animals has been used for measuring the mutagenicity of dietary glycosides. However, the fecalase activity between individuals is significantly different and its preparation is laborious and odious. Therefore, we developed a fecal microbial enzyme mix (FM) usable in the Ames test to remediate the fluctuated reaction system activating natural glycosides to mutagens. We selected, cultured, and mixed 4 bacteria highly producing glycosidase activities based on a cell-free extract of feces (fecalase) from 100 healthy Korean volunteers. When the mutagenicities of rutin and methanol extract of the flos of Sophora japonica L. (SFME), of which the major constituent is rutin, towards Salmonella typhimurium strains TA 98, 100, 102, 1,535, and 1,537 were tested using FM and/or S9 mix, these agents were potently mutagenic. These mutagenicities using FM were not significantly different compared with those using Korean fecalase. SFME and rutin were potently mutagenic in the test when these were treated with fecalase or FM in the presence of S9 mix, followed by those treated with S9 mix alone and those with fecalase or FM. Freeze-dried FM was more stable in storage than fecalase. Based on these findings, FM could be usable instead of human fecalase in the Ames test.

  9. Mutagens and carcinogens - Occurrence and role during chemical and biological evolution

    NASA Technical Reports Server (NTRS)

    Giner-Sorolla, A.; Oro, J.

    1981-01-01

    The roles of mutagenic and carcinogenic substances in early biologic evolution is examined, along with terrestrial and extraterrestrial sources of mutagens and carcinogens. UV solar radiation is noted to have served to stimulate prebiotic life while also causing harmful effects in plants and animals. Aromatic compounds have been found in meteorites, and comprise leukemogens, polycyclic hydrocarbons, and nitrasamine precursors. Other mutagenic sources are volcanoes, and the beginning of evolution with mutagenic substances is complicated by the appearance of malignancies due to the presence of carcinogens. The atmosphere of the Precambrian period contained both mutagens and early carcinogens and, combined with volcanic activity discharges, formed an atmospheric chemical background analogous to the background ionizing radiation. Carcinogenesis is concluded to be intrinsic to nature, having initiated evolution and, eventually, cancer cells.

  10. The mutagenicity of cassava (Manihot esculenta Crantz) preparations.

    PubMed

    De Meester, C; Rollmann, B; Mupenda, K; Mary, Y

    1990-01-01

    Different cassava products were found to contain mutagenic activities in the Ames test. This paper describes how the flavonol quercetin is released during the cooking of fresh cassava leaves, following a process very similar to culinary habits. The hydrolysis of the glucoside(s) and the release of free quercetin has been followed by the monitoring of mutagenic activities with a simultaneous isolation and purification by thin-layer chromatography. The fluorodensitometric method applied revealed that fresh leaves contained about 1300 mg quercetin per kg wet weight, of which 800 mg were released during a normal cooking process.

  11. Suppression on the mutagenicity of 4-nitroquinoline-N-oxide by the methanol extracts of soybean koji prepared with various filamentous fungi.

    PubMed

    Lin, Chia-Hung; Chou, Cheng-Chun

    2006-07-01

    In this study, solid fermentation of soybean with various GRAS filamentous fungi including Aspergillus sojae BCRC 30103, Aspergillus oryzae BCRC 30222, Aspergillus awamori, Actinomucor taiwanesis and Rhizopus sp. was performed to prepare various soybean kojis. Toxicity, mutagenicity and suppression on the mutagenesis induced by a direct mutagen, 4-nitroquinoline-N-oxide (4-NQO) on Salmonella typhimurium TA 100, by the various methanol extracts of the prepared soybean koji and unfermented soybean were determined and compared. Results revealed that methanol extracts of unfermented soybean and kojis show no toxicity and mutagenic activity within the dose levels examined on test organism. On the other hand, antimutagenic activity against 4-NQO was observed with the extract of unfermented soybean. Furthermore, fermentation, regardless of the starter organism employed, resulted in an enhanced antimutagenic effect on the mutagenesis of 4-NQO by the extracts of the soybean koji. Across the dose range (0.625-5.0 mg/plate) tested, a dose-dependent antimutagenic activity was observed. Antimutagenic activities of the koji extracts varied with starter organism, with A. awamori-prepared koji extract exhibiting the highest rate of suppression on the mutagenicity of 4-NQO. Further study with A. awamori also revealed that fermentation temperature affected the antimutagenic activity of the prepared koji extract. In general, the extract of the A. awamori-soybean koji prepared at 30 degrees C showed a higher antimutagenic activity than those prepared at 25 or 35 degrees C.

  12. Mutagenicity of diesel exhaust particle extracts: influence of fuel composition in two diesel engines

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Clark, C.R.; Henderson, T.R.; Royer, R.E.

    The influence of diesel fuel composition on mutagenicity of exhaust particle associated organic compounds has been investigated using nine fuels varying in aromatic content and distillation properties. The tests were conducted with Oldsmobile Delta-88 and Peugot 504 diesel cars operated according to the EPA Federal Test Procedure. The particulate exhaust from each test was collected on a filter, extracted in dichloromethane and the resulting extract evaluated for mutagenicity in Salmonella strain TA-100. Mutagenicity of extracts of particles collected from the Oldsmobile were highest in the higher aromatic content fuels (> 30%) but similar for intermediate (20%) and low (13%) aromaticmore » content fuels. No influence of aromaticity on mutagenicity was observed in samples collected from the Peugeot under the same conditions. Thus, fuel aromatic content may enhance the production of mutagenic combustion products at higher concentrations, but may be dependent upon engine type. A good correlation was observed between mutagenicity of the particle extracts and the initial boiling point of the fuel (r = 0.89). Gas chromatography/mass spectrometric analysis of the aromatic fraction of the fuels showed that the fuel producing the most mutagenic combustion products was highest in phenanthrene type compounds.« less

  13. Mutagens from the cooking of food. II. Survey by Ames/Salmonella test of mutagen formation in the major protein-rich foods of the American diet.

    PubMed

    Bjeldanes, L F; Morris, M M; Felton, J S; Healy, S; Stuermer, D; Berry, P; Timourian, H; Hatch, F T

    1982-08-01

    The formation of mutagens in the major cooked protein-rich foods in the US diet was studied in the Ames Salmonella typhimurium test. The nine protein-rich foods most commonly eaten in the USA--ground beef, beef steak, eggs, pork chops, fried chicken, pot-roasted beef, ham, roast beef and bacon--were examined for their mutagenicity towards S. typhimurium TA1538 after normal 'household' cooking (deep frying, griddle/pan frying, baking/roasting, broiling, stewing, braising or boiling of 100-475 degrees C). Well-done fried ground beef, beef steak, ham pork chops and bacon showed significant mutagen formation. For chicken and beef steak high-temperature broiling produced the most mutagenicity, followed by baking/roasting and frying. Stewing, braising and deep frying produced little mutagen. Eggs and egg products produced mutagens only after cooking at high temperatures (the yolk to a greater extent than the white). Commercially cooked hamburgers showed a wide range of mutagenic activity. We conclude that mutagen formation following cooking of protein-containing foods is a complex function of food type, cooking time and cooking temperature. It seems clear that all the major protein-rich foods if cooked to a well-done state on the griddle (eggs only at temperatures above 225 degrees C) or by broiling will contain mutagens detectable by the Ames/Salmonella assay. This survey is a step towards determining whether any human health hazard results from cooking protein-rich foods. Further testing in both short- and long-term genotoxicity bioassays and carcinogenesis assays are needed before any human risk extrapolations can be made.

  14. Physical factors affecting the mutagenicity of fly ash from a coal-fired power plant.

    PubMed

    Fisher, G L; Chrisp, C E; Raabe, O G

    1979-05-25

    The two finest, most respirable coal fly ash fractions collected from the smokestack of a power plant were more mutagenic than two coarser fractions. Mutagenicity was evaluated in the histidine-requiring bacterial strains TA 1538, TA 98, and TA 100 of Salmonella typhimurium. Ash samples collected from the hoppers of an electrostatic precipitator in the plant were not mutagenic. The mutagens in coal fly ash were resistant to x-ray or ultraviolet irradiation, possibly as a result of stabilization by fly ash surfaces. All mutagenic activity is lost with heating to 350 degrees C.

  15. Mutagenicity evaluation of metal oxide nanoparticles by the bacterial reverse mutation assay.

    PubMed

    Pan, Xiaoping; Redding, James E; Wiley, Patricia A; Wen, Lisa; McConnell, J Scott; Zhang, Baohong

    2010-03-01

    Nanomaterials have been emerging as a new group of contaminants in the environment. We reported the use of a bacterial reverse mutation assay (Ames assay) to evaluate the mutagenicity of five metal oxide nanoparticles Al(2)O(3), Co(3)O(4), CuO, TiO(2), and ZnO in this study. Results showed the mutagenicity was negative for four nanoparticles (Al(2)O(3), Co(3)O(4), TiO(2), and ZnO) up to 1000mug/plate to all three tested strains without S9 metabolic activation. Using a preincubation procedure and high S9 (9%) activation, TiO(2) and ZnO induced marginal mutagenesis to strain Escherichia coli WP2 trp uvrA. CuO displayed low mutagenic potential to Salmonella typhimurium TA97a and TA100 at specific concentrations. However, the colony inhibition effect of CuO was predominant to the strain E. coli WP2 trp uvrA. A dose-dependent inhibition of Escherichia coli WP2 colony was found under CuO exposure at concentration range of 100-1600mug/plate. No growth inhibition of tested bacterial strains by Al(2)O(3), Co(3)O(4), and ZnO was observed at the concentrations used. Published by Elsevier Ltd.

  16. Mutagenicity of food-derived carcinogens and the effect of antioxidant vitamins.

    PubMed

    Montgomery, Beverly A; Murphy, Jessica; Chen, James J; Desai, Varsha G; McGarrity, Lynda; Morris, Suzanne M; Casciano, Daniel A; Aidoo, Anane

    2002-01-01

    The food-derived heterocyclic amines (HCAs) 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are mutagenic in the Ames test and produce tumors in laboratory animals, including monkeys. These HCAs have also been shown to induce gene mutations in vivo. To assess the antimutagenic effects of dietary antioxidant vitamins, beta-carotene, ascorbic acid (vitamin C), and alpha-tocopherol (vitamin E), on food-borne mutagenes/carcinogens, we evaluated the mutagenic activity of the compounds alone or combined with antioxidant vitamins. We utilized the rat lymphocyte mutation assay at the hypoxanthine guanine phosphoribosyl transferase (Hprt) locus. Female Fischer 344 rats treated with different doses (0, 2.5, 5.0, 25.0, and 50.0 mg/kg) of the carcinogens were sacrificed 5 wk after mutagen treatment. Although IQ and MeIQ slightly increased mutation frequency (MF) at some doses, a significant (P < 0.0009) increase in MF was found in animals exposed to MeIQx at 25 mg/kg. PhIP was the most mutagenic of the HCAs, with increases (P < 0.0001) in MF detected at all dose levels compared with controls. Because PhIP was the most mutagenic, it was selected for studies using the dietary antioxidant vitamins. Addition of antioxidant vitamins, singly or in a mixture, caused a significant (P < 0.0001) decrease in PhIP-induced Hprt MF. Vitamin E was the most effective at decreasing Hprt MF. In addition, we determined whether carcinogen metabolism would be affected by ingestion of vitamins. The activities of endogenous detoxification enzymes, glutathione S-transferase and glutathione peroxidase (GPx), were thus examined. Intake of beta-carotene and vitamin C without the carcinogen resulted in an increase (P < 0.05) in GPx activity. Also a modest increase in GPx activity was seen in animals that received the antioxidant mixture alone

  17. Predictive Models for Carcinogenicity and Mutagenicity ...

    EPA Pesticide Factsheets

    Mutagenicity and carcinogenicity are endpoints of major environmental and regulatory concern. These endpoints are also important targets for development of alternative methods for screening and prediction due to the large number of chemicals of potential concern and the tremendous cost (in time, money, animals) of rodent carcinogenicity bioassays. Both mutagenicity and carcinogenicity involve complex, cellular processes that are only partially understood. Advances in technologies and generation of new data will permit a much deeper understanding. In silico methods for predicting mutagenicity and rodent carcinogenicity based on chemical structural features, along with current mutagenicity and carcinogenicity data sets, have performed well for local prediction (i.e., within specific chemical classes), but are less successful for global prediction (i.e., for a broad range of chemicals). The predictivity of in silico methods can be improved by improving the quality of the data base and endpoints used for modelling. In particular, in vitro assays for clastogenicity need to be improved to reduce false positives (relative to rodent carcinogenicity) and to detect compounds that do not interact directly with DNA or have epigenetic activities. New assays emerging to complement or replace some of the standard assays include VitotoxTM, GreenScreenGC, and RadarScreen. The needs of industry and regulators to assess thousands of compounds necessitate the development of high-t

  18. Carcinogenicity and Mutagenicity Data: New Initiatives to ...

    EPA Pesticide Factsheets

    Currents models for prediction of chemical carcinogenicity and mutagenicity rely upon a relatively small number of publicly available data resources, where the data being modeled are highly summarized and aggregated representations of the actual experimental results. A number of new initiatives are underway to improve access to existing public carcinogenicity and mutagenicity data for use in modeling, as well as to encourage new approaches to the use of data in modeling. Rodent bioassay results from the NIEHS National Toxicology Program (NTP) and the Berkeley Carcinogenic Potency Database (CPDB) have provided the largest public data resources for building carcinogenicity prediction models to date. However, relatively few and limited representations of these data have actually informed existing models. Initiatives, such as EPA's DSSTox Database Network, offer elaborated and quality reviewed presentations of the CPDB and expanded data linkages and coverage of chemical space for carcinogenicity and mutagenicity. In particular the latest published DSSTox CPDBAS structure-data file includes a number of species-specific and summary activity fields, including a species-specific normalized score for carcinogenic potency (TD50) and various weighted summary activities. These data are being incorporated into PubChem to provide broad

  19. A method for the detection of protein-bound mutagens in food.

    PubMed

    Ibe, F I; Blowers, S D; Anderson, D; Massey, R

    1994-01-01

    To investigate the possible presence of protein-bound mutagens in food an analytical procedure has been devised in which the sample is enzymically hydrolysed, fractionated by HPLC and examined by a modified liquid incubation Ames assay. To validate the method MeIQx was added, as a model compound, to beefburger and a recovery of 82% obtained. The limit of detection for protein-bound mutagens was 1 microgram/kg, expressed as equivalents of MeIQx. No detectable mutagenicity was observed when the procedure was applied to samples of well cooked beefburger, irradiated chicken or mycoprotein.

  20. The mutagenicities of safrole, estragole, eugenol, trans-anethole, and some of their known or possible metabolites for Salmonella typhimurium mutants.

    PubMed

    Swanson, A B; Chambliss, D D; Blomquist, J C; Miller, E C; Miller, J A

    1979-04-01

    Safrole, estragole, anethole, and eugenol and some of their known or possible metabolites were tested for mutagenic activity for S. typhimurium TA1535, TA100, and TA98. Highly purified 1'-hydroxyestragole and 1'-hydroxysafrole were mutagenic (approximately 15 and 10 revertants/micromole, respectively) for strain TA100 in the absence of fortified liver microsomes; trans-anethole and estragole appeared to have very weak activity. 3'-Hydroxyanethole was too toxic for an adequate test. Supplementation with NADPH-fortified rat-liver microsomes and cytosol converted 3'-hydroxyanethole to a mutagen(s) and increased the mutagenic activities for strain TA100 of 1'-hydroxyestragole, 1'-hydroxysafrole, estragole, and anethole. No mutagenicity was detected for safrole or eugenol with or without added NADPH-fortified liver preparations. The electrophilic 2',3'-oxides of safrole, 1'-hydroxysafrole, 1'-acetoxysafrole, 1'-oxosafrole, estragole, 1'-hydroxyestragole, and eugenol showed dose-dependent mutagenic activities for strain TA1535 in the absence of fortified liver microsomes. These mutagenic activities ranged from about 330 revertants/micromole for 1'-oxosafrole-2',3'-oxide to about 7000 revertants/micromole for safrole-2',3'-oxide. The arylalkenes, their hydroxylated derivatives, or their epoxides did not show mutagenic activity for strain TA98, except for 1'-oxosafrole-2',3'-oxide, which had weak activity. Since the arylalkenes are hydroxylated and/or epoxidized by hepatic microsomes, hydroxy and epoxide derivatives appear to be proximate and ultimate mutagenic metabolites, respectively, of the arylalkenes.

  1. Plant composition, pharmacological properties and mutagenic evaluation of a commercial Zulu herbal mixture: Imbiza ephuzwato.

    PubMed

    Ndhlala, A R; Finnie, J F; Van Staden, J

    2011-01-27

    9 enzyme mixture. The observed activities of some plant extracts, if supported by other confirmatory tests, may justify their inclusion in the makeup of Imbiza ephuzwato herbal mixture as well as their use in traditional medicine. Further studies aimed at investigating possible synergistic effects as a result of mixing plant extracts are necessary. The reported mutagenicity in Imbiza ephuzwato could be as a result of interaction of biomolecules in the heterogeneous mixture, yielding compounds that are converted to mutagenic agents by xenobiotic metabolizing enzymes. It is therefore important to carry out further studies aimed at identifying and eliminating the sources of the mutagenic compounds in the heterogeneous mixture. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  2. Mutagenicity of 1-nitropyrene metabolites from lung S9.

    PubMed

    King, L C; Kohan, M J; Ball, L M; Lewtas, J

    1984-04-01

    The mutagenicity of 1-nitropyrene metabolites from rabbit lung S9 incubates was evaluated using the Salmonella typhimurium plate incorporation assay with strain TA98, with and without Aroclor-induced rat liver S9. The following metabolites were isolated, identified and quantitated by HPLC: 1-nitropyrene -4,5- or -9,10-dihydrodiol (K-DHD), N-acetyl-1-aminopyrene ( NAAP ), 1-aminopyrene (1-AMP), 10-hydroxy-1-nitropyrene, 4-, 5-, 6-, 8- or 9-monohydroxy-1-nitropyrene (phenols) and 3-hydroxy-1-nitropyrene. The predominant metabolites formed by lung S9 incubates were K-DHD, 3-OH-1-nitropyrene and phenols. All of the metabolites were mutagenic in the absence of the exogenous rat liver S9 metabolic activation system, and several, including two unidentified metabolites were more potent than the parent 1-nitropyrene. The mutagenicity of 3 of the metabolites ( NAAP , 10-OH-1-nitropyrene and phenols) were enhanced by S9 while most of the other metabolites were less mutagenic in the presence of S9. These results indicate that lung tissue is capable of both oxidative and reductive metabolism which produced mutagenic metabolites, several of which were more potent than the parent compound, 1-NP.

  3. In vitro mutagenic, antimutagenic, and antioxidant activities evaluation and biotransformation of some bioactive 4-substituted 1-(2-methoxyphenyl)piperazine derivatives.

    PubMed

    Słoczyńska, Karolina; Pańczyk, Katarzyna; Waszkielewicz, Anna M; Marona, Henryk; Pękala, Elżbieta

    2016-12-01

    In vitro mutagenic, antimutagenic, and antioxidant potency evaluation and biotransformation of six novel 4-substituted 1-(2-methoxyphenyl)piperazine derivatives demonstrating antidepressant-like activity were investigated. Mutagenic and antimutagenic properties were assessed using the Ames test; free radical scavenging activity was evaluated with 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay and biotransformation was performed with liver microsomes. It was found that all tested compounds are not mutagenic in bacterial strains TA100 and TA1535 and exhibit antimutagenic effects in the Ames test. Noteworthy, compounds possessing propyl linker between phenoxyl and N-(2-methoxyphenyl)piperazine displayed more pronounced antimutagenic properties than derivatives with ethoxyethyl linker. Additionally, compounds 2 and 6 in vitro biotransformation showed that primarily their hydroxylated or O-dealkylated metabolites are formed. Some of the compounds exhibited intrinsic clearance values lower than those reported previously for antidepressant imipramine. To sum up, the results of the present study might represent a valuable step in designing and planning future studies with piperazine derivatives. © 2016 Wiley Periodicals, Inc.

  4. Mutagenicity of diesel exhaust particle extracts: influence of fuel composition in two diesel engines

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Clark, C.R.; Henderson, T.R.; Royer, R.E.

    The influence of diesel fuel composition on mutagenicity of exhaust particle associated organic compounds has been investigated using nine fuels varying in aromatic content and distillation properties. The tests were conducted with Oldsmobile Delta-88 and Peugot 504 diesel cars operated according to the EPA Federal Test Procedure. The particulate exhaust from each test was collected on a filter, extracted in dichloromethane and the resulting extract evaluated for mutagenicity in Salmonella strain TA-100. Mutagenicity of extracts of particles collected from the Oldsmobile were highest in the higher aromatic content fuels (greater than 30%) but similar for intermediate (20%) and low (13%)more » aromatic content fuels. No influence of aromaticity on mutagenicity was observed in samples collected from the Peugeot under the same conditions. Thus, fuel aromatic content may enhance the production of mutagenic combustion products at higher concentrations, but may be dependent upon engine type. A good correlation was observed between mutagenicity of the particle extracts and the initial boiling point of the fuel (r . 0.89). Gas chromatography/mass spectrometric analysis of the aromatic fraction of the fuels showed that the fuel producing the most mutagenic combustion products was highest in phenanthrene type compounds.« less

  5. Cytotoxicity and mutagenicity of Kevlar: an in vitro evaluation.

    PubMed

    Wening, J V; Marquardt, H; Katzer, A; Jungbluth, K H; Marquardt, H

    1995-03-01

    Toxicity and mutagenicity of Kevlar 49 (PPPT; poly-para-phenylene-terephthalamide) was tested in six strains of Salmonella typhimurium (Ames test; TA97, TA98, TA100, TA102, TA1535, TA1537) with and without an external metabolic activation system (S9), as well as in a mammalian cell mutagenesis assay using V79 Chinese hamster cells. For the Ames test, liquid preincubation, which is considered particularly sensitive, was used. The cells were incubated for 24 h at a temperature of 37 degrees C either directly with Kevlar49 or with ethanol- or chloroform-extracted Kevlar49. The experiments were performed at least twice. The Ames test with six different Salmonella typhimurium strains featuring either base pair substitution or frameshift mutations revealed no cytotoxic or mutagenic activity of Kevlar49. In the mammalian cell mutagenesis assay, using 8-azaguanine (AG) as a selective agent, Kevlar49 was also devoid of cytotoxic or mutagenic activity. Both tests have to be regarded as an initial exploratory screening due to the chosen testing conditions and should be supplemented by tests at different temperatures.

  6. Evaluation of mutagenic and antimutagenic activities of neem (Azadirachta indica) seed oil in the in vitro Ames Salmonella/microsome assay and in vivo mouse bone marrow micronucleus test.

    PubMed

    Vinod, V; Tiwari, P K; Meshram, G P

    2011-04-12

    The possible mutagenic and antimutagenic activity of neem oil (NO) and its DMSO extract (NDE) were, examined in the Ames Salmonella/microsome mutagenicity test and the mouse bone marrow micronucleus assay. Eight different strains of Salmonella typhimurium were, used to study the genotoxicity of neem oil both in the presence and absence of Aroclor-1254 induced rat liver homogenate (S9). Two-dose treatment protocol was, employed to study the cytogenetic activity in micronucleus assay. Similarly, the antimutagenic activity of neem oil and NDE was studied against mitomycin (MMC) and 7,12-dimethylbenz[a]anthracene (DMBA) in the above two test systems. Neem oil was non-mutagenic in all the eight tester strains of Salmonella typhimurium both in the presence and absence of S9 mix. In the present study, there was no significant increase in the frequency of micronucleated polychromatic erythrocytes (MNPCEs) in neem oil treated groups over the negative control (DMSO) group of animals, indicating the non-clastogenic activity of neem oil in the micronucleus test. Neem oil showed good antimutagenic activity against DMBA induced mutagenicity compared to its DMSO extract. However, neem oil showed comparatively less antimutagenicity against MMC in the Ames assay. In vivo anticlastogenic assays shows that neem oil exhibited better activity against DMBA induced clastogenicity. These results indicate non-mutagenic activity of neem oil and significant antimutagenic activity of neem oil suggesting its pharmacological importance for the prevention of cancer. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  7. Food mutagens: The role of cooked food in genetic changes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1995-07-01

    Of all the toxic substances producing during cooking, the most important are likely to be the heterocyclic amines. For 17 years, LLNL researchers have been identifying these food mutagens, measuring their abundance in cooked foods typical of the Western diet, working to understand how they can trigger malignant tumors in laboratory animals that have been exposed to high mutagen doses, and estimating the importance of human exposures. Our success is largely a function of the interdisciplinary approach we have taken to quantify food mutagens and to study their biological effects. LLNL investigators were the first to identify five of themore » most important mutagens in heated food, including PhIP and DiMeIQx. We have shown that fried beef may be the most important single source of heterocyclic amines in the human diet and the PhIP accounts for most of the combined mass of mutagens in fried beef cooked well-done. Most nonmeat foods contain low or undetectable levels of these types of compounds, but some cooked protein-containing foods, such as those high in wheat gluten, have significant levels of unknown aromatic amine mutagens. Cooking time and temperature significantly affect the amounts of mutagens generated. For example, reducing the frying temperature of ground beef from 250 to 200{degrees}C lowers the mutagenic activity by six- to sevenfold. Microwave pretreatment of meat and discarding the liquid that is formed also greatly reduces the formation of heterocyclic amines. Our related work on dose and risk assessment will be described in a forthcoming article.« less

  8. Influence of ozonation on the in vitro mutagenic and toxic potential of secondary effluents.

    PubMed

    Petala, M; Samaras, P; Zouboulis, A; Kungolos, A; Sakellaropoulos, G P

    2008-12-01

    Reclamation of municipal effluents by advanced treatment processes is an attractive perspective for facing certain water shortage problems. However, the application of tertiary techniques should be thoroughly examined for their potential hazardous effects. Ozonation is an efficient chemical oxidation method, often used in wastewater reclamation, which may result in by-products that may alter the toxic and mutagenic properties of effluents. In this study, Ames test and Microtox test were used for the evaluation of ozonation efficiency to upgrade secondary effluents quality. In general, the toxic response and mutagenic effect without metabolic activation of test species were influenced mainly by the ozone dose and ozonation duration, whereas the mutagenic effect with metabolic activation was influenced mainly by ozone dose, indicating that ozone conditions strongly affect the formation of by-products. In most cases, the toxicity was increased and reached up to 100% (in relation to that of secondary effluent) after ozonation with 8.0 mg O3/L for 5 min. On the contrary, in most cases the mutagenic activity towards strain TA98 without metabolic activation was reduced, when ozone dose and contact time increased. However, the mutagenicity was also increased after ozonation at low ozone doses and for contact times less than 5 min. The mutagenic activity of treated effluents towards strain TA98 with metabolic activation remained about the same or was reduced, compared to that of secondary effluent, and was even eliminated after ozonation with 8.0 mg O3/L for contact times higher than 5 min.

  9. An Integrated View of Air Mutagenicity

    EPA Science Inventory

    The mutagenic potency of ambient air particulate material (PM) in the Salmonella mutagenicity assay (revertants/mg PM) varies only ~1 order of magnitude worldwide; however, the mutagenic potency of the air itself (revertants/m3 of air) varies ~5 orders of magnitude (IARC Monograp...

  10. Mutagenicity of Cookstove Emissions

    EPA Science Inventory

    The presentation by David DeMarini will focus on emission factors, including mutagenicity, for 3 stoves. It will correlate the emission factors to assess the health safety of the stove systems and place the mutagenicity emission factor in context with that of other combustion em...

  11. Crude cacao Theobroma cacao extract reduces mutagenicity induced by benzo[a]pyrene through inhibition of CYP1A activity in vitro.

    PubMed

    Ohno, Marumi; Sakamoto, Kentaro Q; Ishizuka, Mayumi; Fujita, Shoichi

    2009-08-01

    Polyphenols have been shown to have potent antioxidant activity, and therefore, food containing polyphenols is expected to contribute to the prevention of cancer. However, food contains not only polyphenols but also various other constituents. We used the Ames test to investigate the effects of crude extracts of whole cacao products, which are known to be rich in polyphenols, on the mutagenicity of benzo[a]pyrene (B[a]P) in Salmonella typhimurium strain TA 98 and tert-butyl hydroperoxide (t-BuOOH) in S. typhimurium strain TA 102. B[a]P induces mutagenicity by metabolic activation and t-BuOOH induces it by generation of free radicals. While white chocolate did not modulate the numbers of revertant colonies produced by B[a]P treatment, milk chocolate and cacao powder extracts did. On the other hand, surprisingly, none of the cacao products tested affected the number of revertant colonies when t-BuOOH was used as the mutagen. At maximum concentration (13.25 mg cacao powder/ml), the crude cacao powder extract reduced ethoxyresorufin O-deethylase activity to 17.4% of the control, suggesting that whole cacao products inhibit cytochrome P450 (CYP) 1A activity. In conclusion, inhibition of CYP1A activity by cacao products may prevent DNA damage by reducing metabolic activation of carcinogens. Copyright 2009 John Wiley & Sons, Ltd.

  12. Separation of mutagenic components in synthetic crudes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Guerin, M. R.; Ho, C. H.; Clark, B. R.

    1978-01-01

    Mutagenic, basic constituents of a synthetic coal oil and a shale oil were isolated from the crude mixtures. In arriving at an efficient isolation procedure, several liquid chromatographic packing-eluent combinations were tried and the fractions bioassayed to determine the distributions of the mutagenic components. The most effective separation was achieved using a sequential elution scheme with first an alumina-benzene combination followed by a Sephadex LH-20 gel-isopropanol-acetone system. About 75 to 80% of an ether soluble base is eluted with benzene through alumina (activity I). Analysis of this fraction has revealed a wide range of alkyl substituted quinolines and pyridines. Materialmore » remaining on the alumina column was eluted with ethanol, dried and placed on the Sephadex column. Isopropanol (approximately 250 ml) and acetone (approximately 600 ml) were used in that order to elute the material quantitatively. About 12% of the ether-soluble base is eluted with the isopropanol while the rest (approximately 10%) is eluted with the acetone. Additional alkyl pyridine compounds are eluted with isopropanol while the acetone fractions are predominantly multi-ring nitrogen heterocyclic compounds, according to mass spectral analyses. Bioassay data show excellent isolation of the mutagenic activities into the acetone fractions. Negligible activity is found in the sum of the other (90% wt) fractions.« less

  13. Mutagenicity of silver nanoparticles in CHO cells dependent on particle surface functionalization and metabolic activation

    NASA Astrophysics Data System (ADS)

    Guigas, Claudia; Walz, Elke; Gräf, Volker; Heller, Knut J.; Greiner, Ralf

    2017-06-01

    The potential of engineered nanomaterials to induce genotoxic effects is an important aspect of hazard identification. In this study, cytotoxicity and mutagenicity as a function of metabolic activation of three silver nanoparticle (AgNP) preparations differing in surface coating were determined in Chinese hamster ovary (CHO) subclone K1 cells. Three silver nanoparticle preparations ( x 90,0 <30 nm) stabilized with polyoxyethylene glycerol trioleate and polyoxyethylene sorbitan monolaurate (AgPure™), citrate (Citrate-Ag), and polyvinylpyrrolidone (PVP-Ag) were used for the experiments. The cytotoxic effect of AgNPs was assessed with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide) test using different concentrations of nanoparticles, while the mutagenicity was evaluated using the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene mutation assay. The cytotoxicity of all three AgNPs was lower in a cell culture medium containing 10% fetal calf serum (FCS) than in medium without FCS. The HPRT test without metabolic activation system S9 revealed that compared to the other AgNP formulations, citrate-coated Ag showed a lower genotoxic effect. However, addition of S9 increased the mutation frequency of all AgNPs and especially influenced the genotoxicity of Citrate-Ag. The results showed that exogenous metabolic activation of nanosilver is crucial even if interactions of the metabolic activation system, nanosilver, and cells are not really understood up to now.

  14. Evaluation of Genotoxic and Mutagenic Activity of Organic Extracts from Drinking Water Sources

    PubMed Central

    Guan, Ying; Wang, Xiaodong; Wong, Minghung; Sun, Guoping; An, Taicheng; Guo, Jun

    2017-01-01

    An increasing number of industrial, agricultural and commercial chemicals in the aquatic environment lead to various deleterious effects on organisms, which is becoming a serious global health concern. In this study, the Ames test and SOS/umu test were conducted to investigate the potential genotoxicity and mutagenicity caused by organic extracts from drinking water sources. Organic content of source water was extracted with XAD-2 resin column and organic solvents. Four doses of the extract equivalent to 0.25, 0.5, 1 and 2L of source water were tested for toxicity. All the water samples were collected from six different locations in Guangdong province. The results of the Ames test and SOS/umu test showed that all the organic extracts from the water samples could induce different levels of DNA damage and mutagenic potentials at the dose of 2 L in the absence of S9 mix, which demonstrated the existence of genotoxicity and mutagenicity. Additionally, we found that Salmonella typhimurium strain TA98 was more sensitive for the mutagen. Correlation analysis between genotoxicity, Organochlorine Pesticides (OCPs) and Polycyclic Aromatic Hydrocarbons (PAHs) showed that most individual OCPs were frame shift toxicants in drinking water sources, and there was no correlation with total OCPs and PAHs. PMID:28125725

  15. The 10th anniversary of the publication of genes and environment: memoir of establishing the Japanese environmental mutagen society and a proposal for a new collaborative study on mutagenic hormesis.

    PubMed

    Sutou, Shizuyo

    2017-01-01

    The Japanese Environmental Mutagen Society (JEMS) was established in 1972 by 147 members, 11 of whom are still on the active list as of May 1, 2016. As one of them, I introduce some historic topics here. These include 1) establishment of JEMS, 2) the issue of 2-(2-furyl)-3-(3-nitro-2-furyl)acrylamide (AF-2), 3) the Mammalian Mutagenicity Study Group (MMS) and its achievements, and 4) the Collaborative Study Group of the Micronucleus Test (CSGMT) and its achievements. In addition to these historic matters, some of which are still ongoing, a new collaborative study is proposed on adaptive response or hormesis by mutagens. There is a close relationship between mutagens and carcinogens, the dose-response relationship of which has been thought to follow the linear no-threshold model (LNT). LNT was fabricated on the basis of Drosophila sperm experiments using high dose radiation delivered in a short period. The fallacious 60 years-old LNT is applied to cancer induction by radiation without solid data and then to cancer induction by carcinogens also without solid data. Therefore, even the smallest amount of carcinogens is postulated to be carcinogenic without thresholds now. Radiation hormesis is observed in a large variety of living organisms; radiation is beneficial at low doses, but hazardous at high doses. There is a threshold at the boundary between benefit and hazard. Hormesis denies LNT. Not a few papers report existence of chemical hormesis. If mutagens and carcinogens show hormesis, the linear dose-response relationship in mutagenesis and carcinogenesis is denied and thresholds can be introduced.

  16. Mutagenicity evaluation of forty-one metal salts by the umu test.

    PubMed

    Yamamoto, Akiko; Kohyama, Yuko; Hanawa, Takao

    2002-01-01

    Metallic biomaterials implanted in a human body may corrode and wear, releasing metal ions and debris which may induce adverse reactions such as inflammation, allergy, neoplastic formation, developmental malformation, etc. Mutagenicity is a very fundamental and important toxicity related to carcinogenicity and reproductive/developmental toxicity because the damages to genes or DNA can be a cause of carcinogenesis and developmental abnormalities. However, available mutagenic data on metallic ions and compounds are restricted to the number of elements. Therefore, to obtain the systematic data necessary for metal ion mutagenicity, 41 metal salts encompassing 36 metals and 5 metallic elements tested with different valences, were evaluated on their mutagenicity by a microbial test, the umu test. As a result, K(2)Cr(2)O(7), RhCl(3), IrCl(4), and MgCl(2) are positive without metabolic activation. Concentrations having the maximum mutagenic effect (C(max)) are 9.65 x 10(-5), 1.00 x 10(-4), 3.11 x 10(-3), 4.12 x 10(-3) mol. L(-1), respectively. CuCl(2), VCl(3), CuCl, RhCl(3), K(2)Cr(2)O(7), and IrCl(4) are positive with metabolic activation by S-9 mix with C(max) of 1.60 x 10(-5), 3.91 x 10(-5), 1.57 x 10(-4), 2.00 x 10(-4), 3.86 x 10(-4), 1.56 x 10(-2) mol. L(-1), respectively. Thirty-five metal salts were negative for tests performed both with and without metabolic activation, whereas it was impossible to evaluate the mutagenicity of MoCl(5) and ZrCl(4) by the umu test because of their colorimetric reaction to testing reagents. Copyright 2001 John Wiley & Sons, Inc.

  17. Mutagenicity of commercial hair dyes and detection of 2,7-diaminophenazine.

    PubMed

    Watanabe, T; Hirayama, T; Fukui, S

    1990-08-01

    Four commercial oxidative-type hair dye formulations, A, B, C, and D, were treated with hydrogen peroxide (H2O2) to simulate normal conditions of use, and the oxidized hair dyes were tested for their mutagenicity in Salmonella typhimurium TA98 in the presence of a mammalian metabolic activation system (S9 mix). Most of them did not show obvious mutagenicity in the range of 1-25 microliters/plate and all exhibited bactericidal activity at 10 microliters/plate. In order to evaluate the mutagenicity of hair dyes both before and after H2O2 oxidation, rayon linked to a copper-phthalocyanine derivative (blue rayon) was used as an adsorbent for the elimination of interfering bactericidal compounds. Adsorbed compounds on blue rayon were eluted with ammoniacal methanol and eluents were subjected to the Ames test. The mutagenicity of the blue-rayon extracts in TA98 with S9 mix was increased by H2O2 oxidation. The blue-rayon extracts obtained from oxidized A and B were potent mutagens and reverted 334 and 999 colonies/10 microliters of original substance, respectively. In addition, 88 and 249 ng of 2,7-diaminophenazine, which was extremely mutagenic in TA98 with S9 mix, were detected in the extracts of 40 ml of the hair dye formulations A and B, respectively. The mutagenicity in oxidized hair dye formulations was successfully detected by use of blue-rayon extraction. 2,7-Diaminophenazine was only formed in the hair dye formulations containing m-phenylenediamine by H2O2 oxidation. Therefore, attention needs to be paid to the use of m-phenylenediamine as a hair dye component, not only for its own toxicity but also for that of its oxidation products.

  18. Environmental nitration processes enhance the mutagenic potency of aromatic compounds.

    PubMed

    Bonnefoy, Aurélie; Chiron, Serge; Botta, Alain

    2012-05-01

    This work is an attempt to establish if aromatic nitration processes are always associated with an increase of genotoxicity. We determined the mutagenic and genotoxic effects of Benzene (B), Nitrobenzene (NB), Phenol (P), 2-Nitrophenol (2-NP), 2,4-Dinitrophenol (2,4-DNP), Pyrene (Py), 1-Nitropyrene (1-NPy), 1,3-Dinitropyrene (1,3-DNPy), 1,6-Dinitropyrene (1,6-DNPy), and 1,8-Dinitropyrene (1,8-DNPy). The mutagenic activities were evaluated with umuC test in presence and in absence of metabolic activation with S9 mix. Then, we used both cytokinesis-blocked micronucleus (CBMN) assay, in combination with fluorescent in situ hybridization (FISH) of human pan-centromeric DNA probes on human lymphocytes in order to evaluate the genotoxic effects. Analysis of all results shows that nitro polycyclic aromatic hydrocarbons (PAHs) are definitely environmental genotoxic/mutagenic hazards and confirms that environmental aromatic nitration reactions lead to an increase in genotoxicity and mutagenicity properties. Particularly 1-NPy and 1,8-DNPy can be considered as human potential carcinogens. They seem to be significant markers of the genotoxicity, mutagenicity, and potential carcinogenicity of complex PAHs mixtures present in traffic emission and industrial environment. In prevention of environmental carcinogenic risk 1-NPy and 1,8-DNPy must therefore be systematically analyzed in environmental complex mixtures in association with combined umuC test, CBMN assay, and FISH on cultured human lymphocytes. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012. Copyright © 2010 Wiley Periodicals, Inc.

  19. Seasonal and spatial variation of the bacterial mutagenicity of fine organic aerosol in southern california.

    PubMed Central

    Hannigan, M P; Cass, G R; Lafleur, A L; Busby, W F; Thilly, W G

    1996-01-01

    The bacterial mutagenicity of a set of 1993 urban particulate air pollution samples is examined using the Salmonella typhimurium TM677 forward mutation assay. Amibent fine particulate samples were collected for 24 hr every sixth day throughout 1993 at four urban sites, including Long Beach, central Los Angeles, Azusa, and Rubidoux, California, and at an upwind background site on San Nicolas Island. Long Beach and central Los Angeles are congested urban areas where air quality is dominated by fresh emissions from air pollution sources; Azuasa and Rubidoux are located farther downwind and receive transported air pollutants plus increased quantities of the products of atmospheric chemical reactions. Fine aerosol samples from Long Beach and Los Angeles show a pronounced seasonal variation in bacterial mutagenicity per cubic meter of- ambient air, with maximum in the winter and a minimum in the summer. The down-wind smog receptor site at Rubidoux shows peak mutagenicity (with postmitochondrial supernatant but no peak without postmitochondrial supernatant) during the September-October periods when direct transport from upwind sources can be expected. At most sites the mutagenicity per microgram of organic carbon from the aerosol is not obviously higher during the summer photochemical smog period than during the colder months. Significant spatial variation in bacterial mutagenicity is observed: mutagenicity per cubic meter of ambient air, on average, is more than an order of magnitude lower at San Nicolas Island than within the urban area. The highest mutagenicity values per microgram of organics supplied to the assay are found at the most congested urban sites at central Los Angeles and Long Beach. The highest annual average values of mutagenicity per cubic meter of air sampled occur at central Los Angeles. These findings stress the importance of proximity to sources of direct emissions of bacterial mutagens and imply that if important mutagen-forming atmospheric

  20. Toxicity and mutagenicity of hymenoxon, sequiterpene lactone.

    PubMed

    Jones, D H; Kim, H L

    1981-12-01

    The oral LD50 of hymenoxon in Swiss white mice was found to be 241 +/- 37 mg/kg. No significant sex differences were observed. Pretreatment of male mice for 3 days using doses of 50 and 100 mg/kg hymenoxon failed to alter significantly pentobarbital sleeping time. Hymenoxon was found to be a direct-acting mutagen in the Salmonella/mammalian microsome test. Urine samples obtained from hymenoxon-treated mice were found to be negative activity when tested directly and when incubated with beta-glucuronidase. Hymenoxon did not produce lethal DNA damage as measured in the Escherichia coli polA or Bacillus subtilis recombinational assays.

  1. Modulatory effects of Cassia fistula fruits against free radicals and genotoxicity of mutagens.

    PubMed

    Kaur, Sandeep; Kumar, Manish; Kaur, Paramjeet; Kaur, Varinder; Kaur, Satwinderjeet

    2016-12-01

    Cassia fistula L. (Fabaceae) fruits are highly recommended in folklore medicine for curing various ailments. In the current study, methanol (CaFM), hexane (CaFH), chloroform (CaFCl), ethyl acetate (CaFE), butanol (CaFB) and aqueous (CaFA) fractions of C. fistula fruits were investigated for their potential to inhibit the genotoxicity of mutagens and free radicals. The antimutagenicity of fractions was evaluated against the reactive carcinogenic ester generating mutagen, 2-aminofluorene (2-AF) and frame-shift mutation inducing mutagen, 4-nitro-o-phenylenediamine (NPD) in Ames Salmonella typhimurium TA98 tester strain. Among the fractions, CaFE showed strongest protective effect against the mutagenicity of both S9-dependent and direct-acting mutagen with an inhibitory percentage of 81% and 64% at the concentration of 1 × 10 3 and 2.5 × 10 3 respectively. All the fractions were analyzed for free radical scavenging activity using DPPH, nitric oxide, lipid peroxidation and superoxide anion assays. CaFE fraction showed maximum antioxidant activity in comparison to other fractions with an IC 50 of 97.01, 172.36, 144 and 264.79 μg/ml respectively. High performance liquid chromatography showed the presence of catechin, epicatechin and umbelliferone in appreciable amount which may account for its efficacy in combating free radicals and also showed protective effect against the mutagenicity of S9-dependent mutagen, 2-AF. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Mutagenicity and antimutagenicity of extracts of three spices and a medicinal plant in Thailand.

    PubMed

    Higashimoto, M; Purintrapiban, J; Kataoka, K; Kinouchi, T; Vinitketkumnuen, U; Akimoto, S; Matsumoto, H; Ohnishi, Y

    1993-11-01

    Three kinds of spices (caraway, coriander and black pepper seeds) and a medicinal plant called 'tong tak' in Thai (Baliospermum axillar, a species of the spurge family) were fractionated into hot water, methanol and hexane extracts. These extracts were not mutagenic for Salmonella typhimurium strains TA98 and TA100 by the Ames assay. However, when the extracts were treated with nitrite, samples of the water and methanol extracts were mutagenic for strain TA100 without metabolic activation. The mutagenicity of the nitrite-treated methanol and hot water extracts of black pepper was highest (8380 and 22,200 His+ per 0.1 g of spice powder, respectively), and that of the nitrite-treated hot water extracts of caraway and tong tak was moderate. The hot water extracts were examined for their antimutagenic activity against mutagenicity induced by various carcinogens by the Ames assay, using the preincubation technique. The tested samples (equivalent to 1-2 mg of spice powder) reduced the mutagenicity induced by 2.7 nmole (397 ng) of N-methyl-N'-nitro-N-nitrosoguanidine by more than 84%, and that induced by dimethylnitrosamine (1.48 mg) or ICR-170 (10 ng) by 30-60%. However, they did not inhibit the mutagenic activity of 1-nitropyrene, 3-nitrofluoranthene, AF-2, methyl methanesulfonate, N-ethyl-N'-nitro-N-nitrosoguanidine, 2-aminoanthracene, 2-acetylaminofluorene, benzo[a]pyrene or IQ.

  3. Role of Mutagenicity in Asbestos Fiber-Induced Carcinogenicity and Other Diseases

    PubMed Central

    Huang, Sarah X. L.; Jaurand, Marie-Claude; Kamp, David W.; Whysner, John; Hei, Tom K.

    2011-01-01

    The cellular and molecular mechanisms of how asbestos fibers induce cancers and other diseases are not well understood. Both serpentine and amphibole asbestos fibers have been shown to induce oxidative stress, inflammatory responses, cellular toxicity and tissue injuries, genetic changes, and epigenetic alterations in target cells in vitro and tissues in vivo. Most of these mechanisms are believe to be shared by both fiber-induced cancers and noncancerous diseases. This article summarizes the findings from existing literature with a focus on genetic changes, specifically, mutagenicity of asbestos fibers. Thus far, experimental evidence suggesting the involvement of mutagenesis in asbestos carcinogenicity is more convincing than asbestos-induced fibrotic diseases. The potential contributions of mutagenicity to asbestos-induced diseases, with an emphasis on carcinogenicity, are reviewed from five aspects: (1) whether there is a mutagenic mode of action (MOA) in fiber-induced carcinogenesis; (2) mutagenicity/carcinogenicity at low dose; (3) biological activities that contribute to mutagenicity and impact of target tissue/cell type; (4) health endpoints with or without mutagenicity as a key event; and finally, (5) determinant factors of toxicity in mutagenicity. At the end of this review, a consensus statement of what is known, what is believed to be factual but requires confirmation, and existing data gaps, as well as future research needs and directions, is provided. PMID:21534089

  4. Ozonation of mutagenic and carcinogenic polyaromatic amines and polyaromatic hydrocarbons in water

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Burleson, G.R.; Caulfield, M.J.; Pollard, M.

    1979-06-01

    The Salmonella-microsome assay for mutagenesis was used to determine the effect of ozone on the mutagenesis of selected carcinogens and mutagens in water. Short periods of ozonation were shown to completely inactivate the mutagenicity of several polyaromatic amine mutagens including acriflavine, proflavine, and beta-naphthylamine. Selected polyaromatic hydrocarbons were also sensitive to ozonation. Kinetic studies revealed that the mutagenicity of benzo(a)pyrene, 3-methylcholanthrene, and 7,12-dimethylbenz(a)anthracene was destroyed after short periods of ozonation. To correlate loss of mutagenicity with loss of carcinogenicity, two polyaromatic hydrocarbons were treated with ozone, extracted from water with hexane, and tested for carcinogenicity in mice. When 7,12-dimethyl-benz(a)anthracene andmore » 3-methyl-cholanthrene were treated with ozone, there was a substantial reduction in carcinogenicity compared to control groups treated with oxygen alone. However, a small number of tumors developed in the group of animals receiving a hexane extract of ozonated 7,12-dimethylbenz(a)anthracene. This activity may be due to breakdown products of 7,12-dimethylbenz(a)anthracene that are not mutagenic.« less

  5. Mutagenic Potential of p-Dithiane.

    DTIC Science & Technology

    1985-08-01

    UNCLASSIFIED FGO 6/29 M 01. JLt * L, mia -l En.25 .4 166 MICROCOP RESOUTION TEST CHART an INSTITUTE REPORT NO. 207 LEC 10 MA20 I--- co DTI ( MUTAGENIC...mg/plate to 0.0016 mg/plate. The test compound was not mutagenic under conditions of this assay. Key Words: Mutagenicity, Genetic Toxicology, Ames...aliquot of the test compound will be retained in the LAIR Archives. TEST SUBSTANCE: p-Dithiane (TA039) INCLUSIVE STUDY DATES: 24 September - 12 October

  6. Emission of polycyclic aromatic hydrocarbons, toxicity, and mutagenicity from domestic cooking using sawdust briquettes, wood, and kerosene.

    PubMed

    Kim, OanhNguyenThi; Nghiem, Le Hoang; Phyu, Yin Latt

    2002-03-01

    Smoke samples, in both gas and particulate matter (PM) phases, of the three domestic stoves were collected using U.S. EPA modified method 5 and were analyzed for 17 PAH (HPLC-UV), acute toxicity (Microtox test), and mutagenicity (Amestest). The gas phase of smoke contributed > or = 95% of 17 PAH, > or = 96% of toxicity, and > or = 60% of mutagenicity. The highest emission factor of 17 PAH was from sawdust briquettes (260 mg/kg), but the highest emission of 11 genotoxic PAH was from kerosene (28 mg/kg). PM samples of kerosene smoke were not toxic. The total toxicity emission factor was the highest from sawdust, followed by kerosene and wood fuel. Smoke samples from the kerosene stove were not mutagenic. TA98 indicated the presence of both direct and indirect mutagenic activities in PM samples of sawdust and wood fuel but only direct mutagenic activities in the gas phase. TA100 detected only direct mutagenic activities in both PM and gas-phase samples. The higher mutagenicity emission factor was from wood fuel, 12 x 10(6) revertants/kg (TA100-S9) and 3.5 x 10(6) (TA98-S9), and lower from sawdust, 2.9 x 10(6) (TA100-S9) and 2.8 x 10(6) (TA98-S9). The low burning rate and high efficiency of a kerosene stove have resulted in the lowest PAH, toxicity, and mutagenicity emissions from daily cooking activities. The bioassays produced toxicity and mutagenicity results in correspondence with the PAH content of samples. The tests could be used for a quick assessment of potential health risks.

  7. A comparison of mutagen production in fried ground chicken and beef: effect of supplemental creatine.

    PubMed

    Knize, M G; Shen, N H; Felton, J S

    1988-11-01

    Ground chicken breast and ground beef with either endogenous or a 10-fold increase in the concentration of creatine were fried at 220 degrees C for 10 min per side. One patty (100 g) of chicken meat yielded 120,000 Salmonella (TA1538) revertants following metabolic activation. The pan residues had 39% of the total activity. Added creatine (10-fold the endogenous level) increased mutagen yields an average of 2-fold. Beef cooked under identical conditions yielded 150,000 revertants/100 g for the meat patties and pan residues combined. Added creatine to beef prior to cooking increased mutagen yields 3-fold. The mutagenic profiles following initial HPLC separation showed that chicken samples with endogenous or added creatine were remarkably similar. Chicken and beef HPLC mutagenicity profiles were also similar to each other, but not identical. This suggests that the general mutagen-forming reactions with the two different types of muscle are qualitatively similar with only minor quantitative differences. The pan residues from both meat types with and without added creatine showed some significant differences in the mutagen peak profile. This work suggests that the types of mutagens formed in chicken are similar to those formed in beef and that creatine appears to be involved in the formation of all the mutagenic compounds produced from fried muscle tissue.

  8. Assessment of the mutagenic potential of ethanol auto engine exhaust gases by the Salmonella typhimurium microsomal mutagenesis assay, using a direct exposure method.

    PubMed

    Lotfi, C F; Brentani, M M; Böhm, G M

    1990-08-01

    The mutagenic activity of the new Brazilian fuel, ethanol, was determined by employing the Salmonella typhimurium microsomal mutagenesis assay (TA97, TA98, TA100, TA102, and TA104) and a direct exposure method. This methodology was first used to determine the mutagenic activity of gasoline, revealing mutagenic activity of base-pair substitution without any need for metabolic activation, indicating the presence of direct-action mutagens. Experiments with ethanol suggest an indirect mutagenic activity of the oxidant type. The exposure system was considered suitable for future studies of gaseous mixtures.

  9. Occurrence of mutagens in canned foods.

    PubMed

    Krone, C A; Iwaoka, W T

    1984-01-01

    Mutagens are shown to be present in a variety of commercially heat-processed foods. Since these substances are not present in the unheated raw material, it appears that they are produced during processing. Canned salmon and beef broth showed the highest mutagenicity while other canned beef and fish products yielded lower but detectable levels. These findings are significant not only because of the large proportion of the food supply which is processed by canning, but also because the mutagens in these foods exhibit chemical behaviors and Salmonella strain specificity similar to mutagens in grilled foods which have been shown to be mammalian carcinogens.

  10. EVALUATION OF NEW 2,2-DIMETHYL-5,5-DIPROPOXYBENZIDINE- AND 3,3-DIPROPOXYBENZIDINE-BASED DIRECT DYE ANALOGS FOR MUTAGENIC ACTIVITY BY USE OF THE SALMONELLA/MAMMALIAN MUTAGENICITY ASSAY

    EPA Science Inventory

    A series of new metallized and unmetallized direct dyes based on benzidine analogs, 2,2'dimethyl-5,5'-dipropoxybenzidine and 3,3'-dipropoxybenzidine, were evaluated for mutagenicity in Salmonella typhimurium strains TA98 and TA100. All of the dyes examined were judged non-mutagen...

  11. Rat liver endothelial and Kupffer cell-mediated mutagenicity and polycyclic aromatic hydrocarbons and aflatoxin B sub 1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Steinberg, P.; Schlemper, B.; Molitor, E.

    The ability of isolated rat liver endothelial and Kupffer cells to activate benzo(a)pyrene (BP), trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (DDBP), trans-1,2-dihydroxy-1,2-dihydrochrysene (DDCH), and aflatoxin B{sub 1} (AFB{sub 1}) to mutagenic metabolites was assessed by means of a cell-mediated bacterial mutagenicity assay and compared with the ability of parenchymal cells to activate these compounds. Endothelial and Kupffer cells from untreated rats were able to activate AFB{sub 1} and DDBP; DDBP was activated even in the absence of an NADPH-generating system. Pretreating the animals with Aroclor 1254 strongly enhanced the mutagenicity of the dihydrodiol, whereas the mutagenicity of AFB{sub 1} showed a slight increase. BP andmore » DDCH were only activated by endothelial and Kupffer cells isolated from Aroclor 1254-pretreated rats. Parenchymal cells form untreated animals activated all four carcinogens tested; Aroclor 1254 enhanced the parenchymal cell-mediated mutagenicity of BP and DDCH but did not affect that of DDBP and clearly reduced that of AFB{sub 1}. The reduced mutagenicity of AFB{sub 1} correlates with the decrease in the amount of 2{alpha}-hydroxytestosterone formed when testosterone was incubated with parenchymal cell microsomes from Aroclor 1254-pretreated rats (compared with microsomes from untreated animals): the formation of 2{alpha}-hydroxytestosterone is specifically catalyzed by cytochrome P-450h, a hemoprotein thought to be involved in the activation of AFB{sub 1}. These results show that not only rat liver parenchymal cells, but also endothelial and Kupffer cells, activated several carcinogens to mutagenic metabolites.« less

  12. Testing by artificial intelligence: computational alternatives to the determination of mutagenicity.

    PubMed

    Klopman, G; Rosenkranz, H S

    1992-08-01

    In order to develop methods for evaluating the predictive performance of computer-driven structure-activity methods (SAR) as well as to determine the limits of predictivity, we investigated the behavior of two Salmonella mutagenicity data bases: (a) a subset from the Genetox Program and (b) one from the U.S. National Toxicology Program (NTP). For molecules common to the two data bases, the experimental concordance was 76% when "marginals" were included and 81% when they were excluded. Three SAR methods were evaluated: CASE, MULTICASE and CASE/Graph Indices (CASE/GI). The programs "learned" the Genetox data base and used it to predict NTP molecules that were not present in the Genetox compilation. The concordances were 72, 80 and 47% respectively. Obviously, the MULTICASE version is superior and approaches the 85% interlaboratory variability observed for the Salmonella mutagenicity assays when the latter was carried out under carefully controlled conditions.

  13. Cytotoxic and mutagenic properties of shale oil byproducts. II. Comparison of mutagenic effects at five genetic markers induced by retort process water plus near ultraviolet light in Chinese hamster ovary cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, D.J.C.; Strniste, G.F.

    1982-01-01

    A Chinese hamster ovary (CHO) cell line heterozygous at the adenine phosphoribosyl transferase (APRT) locus was used for selection of induced mutants resistant to 8-azaadenine (8AA), 6-thioguanine (6TG), ouabain (OUA), emetine (EMT) and diphtheria toxin (DIP). The expression times necessary for optimizing the number of mutants recovered at the different loci have been determined using the known direct acting mutagen, far ultraviolet light (FUV), and a complex aqueous organic mixture (shale oil process water) activated with near ultraviolet light (NUV). The results indicate that optimal expression times following treatment with either mutagen was between 2 and 8 days. For CHOmore » cells treated with shale oil process water and subsequently exposed to NUV a linear dose response for mutant induction was observed for all five genetic loci. At 10% surviving fraction of cells, between 35- and 130-fold increases above backgound mutation frequencies were observed for the various markers examined.« less

  14. Dietary Exposure of Nigerians to Mutagens and Estrogen-Like Chemicals

    PubMed Central

    Omoruyi, Iyekhoetin Matthew; Ahamioje, Derek; Pohjanvirta, Raimo

    2014-01-01

    Food and drinking water are poorly delineated sources of human exposure to chemical food mutagens and endocrine-disrupting chemicals. In this study, we investigated the presence of mutagens and chemicals exhibiting estrogenic activity in the daily diet of Nigerians, using in vitro assays. Commercially processed foods or snacks and various brands of pure water sachets were extracted by solid-phase extraction and liquid-liquid extraction, respectively. Mutagenicity was determined by the conventional Ames test and two complementary assays on two strains of Salmonella (TA 100 and TA 98), while the estrogenic activity was assessed by a yeast bioluminescent assay, using two recombinant yeast strains (Saccharomyces cerevisiae BMAEREluc/ERα and S. cerevisiae BMA64/luc). A third of the food varieties investigated (chin-chin, hamburger, suya and bean cake) were mutagenic in all three assays, either in the presence or absence of S9 mix. Of the packed water samples, five out of the sixteen investigated (31%), were found to be estrogenic, with estradiol and bisphenol A equivalents ranging from 0.79 to 44.0 ng/L and 124.2 to 1,000.8 ng/L, respectively. Hence, although the current situation in Nigeria does not appear to be substantially worse than, e.g., in Europe, regular monitoring is warranted in the future. PMID:25153465

  15. TRENDS OF POLYCYCLIC AROMATIC HYDROCARBON LEVELS AND MUTAGENICITY IN SANTIAGO'S INHALABLE AIRBORNE PARTICLES IN THE PERIOD 1992-1996.

    EPA Science Inventory

    Abstract

    Trends of polycyclic aromatic hydrocarbons (PAHs) for 1992-1996 (cold season) and their mutagenic activity were investigated in organic extracts from the Santiago. Chile. inhalable particles (PM10). The highest PAH concentrations were observed in 1992 and decline...

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

    PubMed

    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.

  17. Chemical characterization and cytotoxic, genotoxic, and mutagenic properties of Baccharis trinervis (Lam, Persoon) from Colombia and Brazil.

    PubMed

    Jaramillo-García, Victoria; Trindade, Cristiano; Lima, Elisiane; Guecheva, Temenouga N; Villela, Izabel; Martinez-Lopez, Wilner; Corrêa, Dione S; Ferraz, Alexandre de B F; Moura, Sidnei; Sosa, Milton Quintana; Da Silva, Juliana; Henriques, João Antônio Pegas

    2018-03-01

    Baccharis trinervis (Lam, Persoon) leaves are used in the traditional medicine for the treatment of high fevers, edema, inflammation, sores and muscle cramps, snakebites and as antiseptic. To investigate the cytotoxic, genotoxic, and mutagenic effects of extracts and fractions of B. trinervis from Brazil and Colombia in Chinese Hamster Ovary (CHO) cells, and to examine the mutagenic activity in Salmonella typhimurium. Aqueous extracts (AE) of aerial parts of B. trinervis from Brazil (B) and Colombia (C) were fractioned in ethyl acetate fraction (EAF), butanol extract (BF), and aqueous residue fraction (ARF). Qualitative chemical screening and determination of total flavonoid content were made. Identification of chemical constituents was performed by High Performance Liquid Chromatography (HPLC) and High Resolution Mass Spectrometry (HRMS). For the in vitro tests, CHO cells were treated for 3h with extracts and fractions. The cytotoxic activity was evaluated by clonal survival and 3-(4.5-dimethylthiazole-2-yl)-2.5-biphenyl tetrazolium bromide reduction assay (MTT). Genotoxic and mutagenic effects were evaluated by the alkaline comet assay and Cytokinesis-blockage micronucleus test (CBMN), respectively. Additionally, Salmonella/microsome assay was carried out to determinate the mutagenic effects in EAF from Brazil and Colombia. Phytochemical analyses indicated the presence of saponins and flavonoids. AE and EAF were the samples with the highest quantity of total flavonoids. HPLC showed the presence of luteolin only in AEC, and caffeic acid, ellagic acid, rosmarinic acid, and rutin were identified in AEB and AEC (AEC>AEB). The HRMS in positive mode of EAFB and EAFC showed presence of two carboxylic acids, coumarin, and two terpenoids. In addition, were identified one terpenoid and two carboxylic acids in AE, BF and ARF of B. trinervis from both countries in negative mode. Dose-dependent cytotoxic effects were observed in CHO cells treated with B. trinervis extracts

  18. Interrelationships among carcinogenicity, mutagenicity, acute toxicity, and chemical structure in a genotoxicity data base

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Benigni, R.; Andreoli, C.; Giuliani, A.

    1989-01-01

    The interrelationships among carcinogenicity, mutagenicity, acute toxicity (LD50), and a number of molecular descriptors were studied by computerized data analysis methods on the data base generated by the International Program for the Evaluation of Short-Term Test for Carcinogens (IPESTTC). With the use of statistical regression methods, three main associations were evidenced: (1) the well-known correlation between carcinogenicity and mutagenicity; (2) a correlation between mutagenicity and toxicity (LD50 ip in mice); and (3) a correlation between toxicity and a recently introduced estimator of the free energy of binding of the molecules to biological receptors. As expected on the basis of themore » large variety of chemical classes represented in the IPESTTC data base, no simple relationship between mutagenicity or carcinogenicity and chemical descriptors was found. To overcome this problem, a new pattern recognition method (REPAD), developed by us for structure-activity studies of noncongeneric chemicals, has been used. This allowed us to highlight a significant difference between the whole patterns of relationships among chemicophysical variables in the two groups to active (mutagenicity and/or carcinogenic) and inactive chemicals. This approach generated a classification rule able to correctly assign about 80% of carcinogens or mutagens.« less

  19. Optimization of the Ames/salmonella mutagenicity assay for use with extracts of aquatic sediments

    USGS Publications Warehouse

    Papoulias, Diana M.; Buckler, Denny R.; Tillitt, Donald E.

    1996-01-01

    Non-mutagenic components interfered with the ability of the standard Ames/salmonella assay to detect mutagenicity in extracts of contaminated Great Lakes sediments. The use of gel permeation chromatography (GPC) to remove these macromolecules from methylene chloride extracts prior to Ames testing enhanced the likelihood of transfer of mutagenic components into dimethyl sulf oxide (the assay solvent). Therefore, to optimize the assay's sensitivity we pre-treated sediment extracts using GPC and increased metabolic activity through the use of a 30% S9 mix. Increasing the level of Aroclor 1254-induced rat liver S9, typically used to metabolically activate promutagens, had the additional beneficial effect of reducing the cytotoxicity of the extracts. As applied in this study, the Ames assay can serve as a sensitive test for screening the mutagenic potential of large numbers of uncharacterized sediment extracts.

  20. Assessment of the Mutagenicity of Sediments from Yangtze River Estuary Using Salmonella Typhimurium/Microsome Assay

    PubMed Central

    Liu, Li; Chen, Ling; Floehr, Tilman; Xiao, Hongxia; Bluhm, Kerstin; Hollert, Henner; Wu, Lingling

    2015-01-01

    Sediments in estuaries are of important environmental concern because they may act as pollution sinks and sources to the overlying water body. These sediments can be accumulated by benthic organisms. This study assessed the mutagenic potential of sediment extracts from the Yangtze River estuary by using the Ames fluctuation assay with the Salmonella typhimurium his (−) strain TA98 (frameshift mutagen indicator) and TA100 (baseshift mutagen indicator). Most of the sediment samples were mutagenic to the strain TA98, regardless of the presence or absence of exogenous metabolic activation (S9 induction by β-naphthoflavone/phenobarbital). However, none of the samples were mutagenic to the strain TA100. Thus, the mutagenicity pattern was mainly frameshift mutation, and the responsible toxicants were both direct (without S9 mix) and indirect (with S9 mix) mutagens. The mutagenicity of the sediment extracts increased when S9 was added. Chemical analysis showed a poor correlation between the content of priority polycyclic aromatic hydrocarbons and the detected mutagenicity in each sample. The concept of effect-directed analysis was used to analyze possible compounds responsible for the detected mutagenic effects. With regard to the mutagenicity of sediment fractions, non-polar compounds as well as weakly and moderately polar compounds played a main role. Further investigations should be conducted to identify the responsible components. PMID:26606056

  1. Mutagenicity of diesel exhaust particles and oil shale particles dispersed in lecithin surfactant.

    PubMed

    Wallace, W E; Keane, M J; Hill, C A; Xu, J; Ong, T M

    1987-01-01

    Diesel exhaust particulate material from exhaust pipe scrapings of two trucks, diluted automobile diesel exhaust particulate material collected on filters, and two oil shale ores were prepared for the Ames mutagenicity assay by dichloromethane (DCM) extraction, by dispersion into 0.85% saline, or by dispersion into dipalmitoyl lecithin (DPL) emulsion in saline. Salmonella typhimurium TA98 was used to detect frameshift mutagens in the samples. Samples of diesel soot gave positive mutagenic responses with both DCM extraction and DPL dispersion, with the DPL dispersion giving higher results in some cases. The results suggest that possible mutagens associated with inhaled particles may be dispersed or solubilized into the phospholipid component of pulmonary surfactant and become active in such a phase.

  2. Mutagenicity assessment of aerosols in emissions from domestic combustion processes.

    PubMed

    Canha, Nuno; Lopes, Isabel; Vicente, Estela Domingos; Vicente, Ana M; Bandowe, Benjamin A Musa; Almeida, Susana Marta; Alves, Célia A

    2016-06-01

    Domestic biofuel combustion is one of the major sources of regional and local air pollution, mainly regarding particulate matter and organic compounds, during winter periods. Mutagenic and carcinogenic activity potentials of the ambient particulate matter have been associated with the fraction of polycyclic aromatic hydrocarbons (PAH) and their oxygenated (OPAH) and nitrogenated (NPAH) derivatives. This study aimed at assessing the mutagenicity potential of the fraction of this polycyclic aromatic compound in particles (PM10) from domestic combustion by using the Ames assays with Salmonella typhimurium TA98 and TA100. Seven biofuels, including four types of pellets and three agro-fuels (olive pit, almond shell and shell of pine nuts), were tested in an automatic pellet stove, and two types of wood (Pinus pinaster, maritime pine, and Eucalyptus globulus, eucalypt) were burned in a traditional wood stove. For this latter appliance, two combustion phases-devolatilisation and flaming/smouldering-were characterised separately. A direct-acting mutagenic effect for the devolatilisation phase of pine combustion and for both phases of eucalypt combustion was found. Almond shell revealed a weak direct-acting mutagenic effect, while one type of pellets, made of recycled wastes, and pine (devolatilisation) presented a cytotoxic effect towards strain TA100. Compared to the manually fired appliance, the automatic pellet stove promoted lower polyaromatic mutagenic emissions. For this device, only two of the studied biofuels presented a weak mutagenic or cytotoxic potential.

  3. Mutagenicity of fume particles from stainless steel welding.

    PubMed

    Hedenstedt, A; Jenssen, D; Lidestein B-M; Ramel, C; Rannug, U; Stern, R M

    1977-12-01

    Welding fume particles collected from different welding procedures were tested for mutagenicity in Escherichia coli, with the inhibition zone in pol A- as compared to pol A+, and in Salmonella typhimurium, TA 100 strain. While no mutagenicity was found with mild steel welding, a mutagenic effect was established with samples from stainless steel welding. This mutagenicity was particularly associated with manual metal arc (MMA) welding, and less so with metal inert-gas welding. A decrease in or an elimination of the effect occurred with a liver microsomal metabolizing system (S-9 mix). The MMA samples produced the strongest mutagenic effect. More-detailed investigations on these samples showed that the mutagenic agent(s) is water soluble. An increased mutagenicity, which also revealed the induction of frame shift mutations, was found with TA 98. The same welding fume sample was used for a mutagenicity test (resistance to 6-thioguanine) with V 79 hamster cells. Because of the high toxicity of these welding fume particles on the cells, only very low concentrations could be tested, but the increase of mutations, when compared to the negative control, was significant. It is suggested that hexavalent chromium may be involved in the mutagenic effect of the welding fumes.

  4. COMPARATIVE MUTAGENICITY OF HALOMETHANES AND HALONITROMETHANES IN SALMONELLA TA100: STRUCTURE-ACTIVITY ANALYSIS AND MUTATION SPECTRA

    EPA Science Inventory

    Halonitromethanes (HNMs) are a recently identified class of disinfection by-products (DPBs) in drinking water that are mutagenic in Salmonella and potent inducers of DNA strand breaks in mammalian cells. Here we compared the mutagenic potencies of the HNMs to those of their halom...

  5. Extending (Q)SARs to incorporate proprietary knowledge for regulatory purposes: A case study using aromatic amine mutagenicity.

    PubMed

    Ahlberg, Ernst; Amberg, Alexander; Beilke, Lisa D; Bower, David; Cross, Kevin P; Custer, Laura; Ford, Kevin A; Van Gompel, Jacky; Harvey, James; Honma, Masamitsu; Jolly, Robert; Joossens, Elisabeth; Kemper, Raymond A; Kenyon, Michelle; Kruhlak, Naomi; Kuhnke, Lara; Leavitt, Penny; Naven, Russell; Neilan, Claire; Quigley, Donald P; Shuey, Dana; Spirkl, Hans-Peter; Stavitskaya, Lidiya; Teasdale, Andrew; White, Angela; Wichard, Joerg; Zwickl, Craig; Myatt, Glenn J

    2016-06-01

    Statistical-based and expert rule-based models built using public domain mutagenicity knowledge and data are routinely used for computational (Q)SAR assessments of pharmaceutical impurities in line with the approach recommended in the ICH M7 guideline. Knowledge from proprietary corporate mutagenicity databases could be used to increase the predictive performance for selected chemical classes as well as expand the applicability domain of these (Q)SAR models. This paper outlines a mechanism for sharing knowledge without the release of proprietary data. Primary aromatic amine mutagenicity was selected as a case study because this chemical class is often encountered in pharmaceutical impurity analysis and mutagenicity of aromatic amines is currently difficult to predict. As part of this analysis, a series of aromatic amine substructures were defined and the number of mutagenic and non-mutagenic examples for each chemical substructure calculated across a series of public and proprietary mutagenicity databases. This information was pooled across all sources to identify structural classes that activate or deactivate aromatic amine mutagenicity. This structure activity knowledge, in combination with newly released primary aromatic amine data, was incorporated into Leadscope's expert rule-based and statistical-based (Q)SAR models where increased predictive performance was demonstrated. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Bioassay-directed fractionation and salmonella mutagenicity of automobile and forklift diesel exhaust particles.

    PubMed Central

    DeMarini, David M; Brooks, Lance R; Warren, Sarah H; Kobayashi, Takahiro; Gilmour, M Ian; Singh, Pramila

    2004-01-01

    Many pulmonary toxicity studies of diesel exhaust particles (DEPs) have used an automobile-generated sample (A-DEPs) whose mutagenicity has not been reported. In contrast, many mutagenicity studies of DEPs have used a forklift-generated sample (SRM 2975) that has been evaluated in only a few pulmonary toxicity studies. Therefore, we evaluated the mutagenicity of both DEPs in Salmonella coupled to a bioassay-directed fractionation. The percentage of extractable organic material (EOM) was 26.3% for A-DEPs and 2% for SRM 2975. Most of the A-EOM (~55%) eluted in the hexane fraction, reflecting the presence of alkanes and alkenes, typical of uncombusted fuel. In contrast, most of the SRM 2975 EOM (~58%) eluted in the polar methanol fraction, indicative of oxygenated and/or nitrated organics derived from combustion. Most of the direct-acting, base-substitution activity of the A-EOM eluted in the hexane/dichloromethane (DCM) fraction, but this activity eluted in the polar methanol fraction for the SRM 2975 EOM. The direct-acting frameshift mutagenicity eluted across fractions of A-EOM, whereas > 80% eluted only in the DCM fraction of SRM 2975 EOM. The A-DEPs were more mutagenic than SRM 2975 per mass of particle, having 227 times more polycyclic aromatic hydrocarbon-type and 8-45 more nitroarene-type mutagenic activity. These differences were associated with the different conditions under which the two DEP samples were generated and collected. A comprehensive understanding of the mechanisms responsible for the health effects of DEPs requires the evaluation of DEP standards for a variety of end points, and our results highlight the need for multidisciplinary studies on a variety of representative samples of DEPs. PMID:15175166

  7. THE MUTAGENICITY OF METALLIZED AND UNMETALLIZED AZO AND FORMAZAN DYES IN THE SALMONELLA MUTAGENICITY ASSAY

    EPA Science Inventory

    The mutagenicity of metallized and unmetallized azo and formazan dyes in the Salmonella mutagenicity
    Laura. C. Edwards', Harold S. Freeman'*, and Larry D. Claxton2

    Abstract
    In previous papers, the synthesis and chemical properties of iron complexed azo and formazan d...

  8. Pharmaceutical wastewater being composite mixture of environmental pollutants may be associated with mutagenicity and genotoxicity.

    PubMed

    Sharif, Ali; Ashraf, Muhammad; Anjum, Aftab Ahmed; Javeed, Aqeel; Altaf, Imran; Akhtar, Muhammad Furqan; Abbas, Mateen; Akhtar, Bushra; Saleem, Ammara

    2016-02-01

    Pharmaceutical industries are amongst the foremost contributor to industrial waste. Ecological well-being is endangered owing to its facile discharge. In the present study, heavy metals and organic contaminants in waste water were characterized using atomic absorption spectrophotometer and GC-MS, respectively. Mutagenicity and genotoxic potential of pharmaceutical waste water were investigated through bacterial reverse mutation assay and in vitro comet assay, respectively. Ames test and comet assay of first sample were carried out at concentrations of 100, 50, 25, 12.5, 6.25 % v/v effluent with distilled water. Chromium (Cr), lead (Pb), arsenic (As), and cadmium (Cd) were found in high concentrations as compared to WHO- and EPA-recommended maximum limits. Arsenic was found to be the most abundant metal and its maximum concentration was 0.8 mg.L(-1). GC-MS revealed the presence of lignocaine, digitoxin, trimethoprim, caffeine, and vitamin E in waste water. Dose-dependent decrease in mutagenic index was observed in both strains. Substantial increase in mutagenicity was observed for TA-100, when assay was done by incorporating an enzyme activation system, whereas a slight increase was detected for TA-102. In vitro comet assay of waste water exhibited decrease in damage index and percentage fragmentation with the increase in dilution of waste water. Tail length also decreased with an increase in the dilution factor of waste water. These findings suggest that pharmaceutical waste water being a mix of different heavy metals and organic contaminants may have a potent mutagenic and genotoxic effect on exposed living organisms.

  9. A Novel Antifungal Is Active against Candida albicans Biofilms and Inhibits Mutagenic Acetaldehyde Production In Vitro

    PubMed Central

    Nieminen, Mikko T.; Novak-Frazer, Lily; Rautemaa, Vilma; Rajendran, Ranjith; Sorsa, Timo; Ramage, Gordon; Bowyer, Paul; Rautemaa, Riina

    2014-01-01

    The ability of C. albicans to form biofilms is a major virulence factor and a challenge for management. This is evident in biofilm-associated chronic oral-oesophageal candidosis, which has been shown to be potentially carcinogenic in vivo. We have previously shown that most Candida spp. can produce significant levels of mutagenic acetaldehyde (ACH). ACH is also an important mediator of candidal biofilm formation. We have also reported that D,L-2-hydroxyisocaproic acid (HICA) significantly inhibits planktonic growth of C. albicans. The aim of the present study was to investigate the effect of HICA on C. albicans biofilm formation and ACH production in vitro. Inhibition of biofilm formation by HICA, analogous control compounds or caspofungin was measured using XTT to measure biofilm metabolic activity and PicoGreen as a marker of biomass. Biofilms were visualised by scanning electron microscopy (SEM). ACH levels were measured by gas chromatography. Transcriptional changes in the genes involved in ACH metabolism were measured using RT-qPCR. The mean metabolic activity and biomass of all pre-grown (4, 24, 48 h) biofilms were significantly reduced after exposure to HICA (p<0.05) with the largest reductions seen at acidic pH. Caspofungin was mainly active against biofilms pre-grown for 4 h at neutral pH. Mutagenic levels (>40 µM) of ACH were detected in 24 and 48 h biofilms at both pHs. Interestingly, no ACH production was detected from D-glucose in the presence of HICA at acidic pH (p<0.05). Expression of genes responsible for ACH catabolism was up-regulated by HICA but down-regulated by caspofungin. SEM showed aberrant hyphae and collapsed hyphal structures during incubation with HICA at acidic pH. We conclude that HICA has potential as an antifungal agent with ability to inhibit C. albicans cell growth and biofilm formation. HICA also significantly reduces the mutagenic potential of C. albicans biofilms, which may be important when treating bacterial-fungal biofilm

  10. [The chiral mutagens: cytogenetic effects on higher plants].

    PubMed

    Morgun, V V; Larchenko, E A; Kostianovskiĭ, R G; Keterinchuk, A M

    2011-01-01

    The paper covers investigation of cytogenetic activity of chiral mutagens and their specific effects on the plant cells chromosomes of soft winter wheat (Triticum aestivum L.). Comparative analysis of cytogenetic activity of chiral NEU: S(+)1-N-nitroso- 1-N-methyl-3-N-sec-buthylureas (S(+)NMsBU) and R(-)1-N-nitroso- 1N-methyl-3-Nsec-buthylureas (R(-)NMsBU) on winter wheat was performed. As it was shown by the frequency of chromosomal aberrations the S(+) stereoisomer was twice more active than R(-). In addition to typical anaphase aberrations (fragments, bridges, lagging chromosomes) the numerous mitosis pathologies were revealed - K-mitoses, hyperspiralization and despiralization of chromosomes, unequal allocation of chromosomes between the daughter nuclei, mass fragmentation, nondisjunction and chromosome adhesion, three-pole mitoses, etc. Neither of the mentioned pathologies was observed under the action of NEU and gamma-rays.

  11. The enhancing effect of ethanol on the mutagenic activation of N-nitrosomethylbenzylamine by cytochrome P450 2A in the rat oesophagus.

    PubMed

    Tatematsu, Kenjiro; Koide, Akihiro; Morimura, Keiichirou; Fukushima, Shoji; Mori, Yukio

    2013-03-01

    Alcohol consumption is frequently associated with various cancers and the enhancement of the metabolic activation of carcinogens has been proposed as a mechanism underlying this relationship. The ethanol-induced enhancement of N-nitrosodiethylamine (DEN)-mediated carcinogenesis can be attributed to an increase in hepatic activity. However, the mechanism of elevation of N-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis remains unclear. To elucidate the mechanism underlying the role of ethanol in the enhancement of NMBA-induced oesophageal carcinogenesis, we evaluated the hepatic and extrahepatic levels of the cytochrome P450 (CYP) and mutagenic activation of environmental carcinogens by immunoblot analyses and Ames preincubation test, respectively, in F344 rats treated with ethanol. Five weeks of treatment with 10% ethanol added to the drinking water or two intragastric treatments with 50% ethanol, both resulted in elevated levels of CYP2E1 (1.5- to 2.3-fold) and mutagenic activities of DEN, N-nitrosodimethylamine and N-nitrosopyrrolidine in the presence of rat liver S9 (1.5- to 2.4-fold). This was not the case with CYP1A1/2, CYP2A1/2, CYP2B1/2 or CYP3A2, nor with the activities of 2-amino-3-methylimidazo[4,5-f]quinoline, 3-amino-1-methyl-5H-pyrido[4,3-b]indole, aflatoxin B(1) or other N-nitroso compounds (NOCs), including NMBA. Ethanol-induced elevations of CYP2A and CYP2E1 were observed in the oesophagus (up to 1.7- and 2.3-fold) and kidney (up to 1.5- and 1.8-fold), but not in the lung or colon. In oesophagus and kidney, the mutagenic activities of NMBA and four NOCs were markedly increased (1.3- to 2.4-fold) in treated rats. The application of several CYP inhibitors revealed that CYP2A were likely to contribute to the enhancing effect of ethanol on NMBA activation in the rat oesophagus and kidney, but that CYP2E1 failed to do so. These results showed that the enhancing effect of ethanol on NMBA-induced oesophageal carcinogenesis could be attributed to an

  12. Mutagenicity of automobile workshop soil leachate and tobacco industry wastewater using the Ames Salmonella fluctuation and the SOS chromotests.

    PubMed

    Okunola, Alabi A; Babatunde, Esan E; Chinwe, Duru; Pelumi, Oyedele; Ramatu, Salihu G

    2016-06-01

    Environmental management of industrial solid wastes and wastewater is an important economic and environmental health problem globally. This study evaluated the mutagenic potential of automobile workshop soil-simulated leachate and tobacco wastewater using the SOS chromotest on Escherichia coli PQ37 and the Ames Salmonella fluctuation test on Salmonella typhimurium strains TA98 and TA100 without metabolic activation. Physicochemical parameters of the samples were also analyzed. The result of the Ames test showed mutagenicity of the test samples. However, the TA100 was the more responsive strain for both the simulated leachate and tobacco wastewater in terms of mutagenic index in the absence of metabolic activation. The SOS chromotest results were in agreement with those of the Ames Salmonella fluctuation test. Nevertheless, the E. coli PQ37 system was slightly more sensitive than the Salmonella assay for detecting genotoxins in the tested samples. Iron, cadmium, manganese, copper, nickel, chromium, arsenic, zinc, and lead contents analyzed in the samples were believed to play significant role in the observed mutagenicity in the microbial assays. The results of this study showed that the simulated leachate and tobacco wastewater showed strong indication of a genotoxic risk. Further studies would be required in the analytical field in order to identify and quantify other compounds not analyzed for in this study, some of which could be responsible for the observed genotoxicity. This will be necessary in order to identify the sources of toxicants and thus to take preventive and/or curative measures to limit the toxicity of these types of wastes. © The Author(s) 2014.

  13. Mutagenic and genotoxic effects of Guelma's urban wastewater, Algeria.

    PubMed

    Tabet, Mouna; Abda, Ahlem; Benouareth, Djamel E; Liman, Recep; Konuk, Muhsin; Khallef, Messaouda; Taher, Ali

    2015-02-01

    Assessment of water pollution and its effect upon river biotic communities and human health is indispensable to develop control and management strategies. In this study, the mutagenicity and genotoxicity of urban wastewater of the city of Guelma in Algeria were examined between April 2012 and April 2013. For this, two biological tests, namely Amesand chromosomal aberrations (CA) test in Allium cepa root tips were employed on the samples collected from five different sampling stages (S1-S5). In Ames test, two strains of Salmonella typhimurium TA98 and TA100 with or without metabolic activation (S9-mix) were used. All water samples were found to be mutagenic to S. typhimurium TA98 with or without S9-mix. A significant decrease in mitotic index (MI) was observed with a decrease in the percentage of cells in the prophase and an increase in the telophase. Main aberrations observed were anaphase bridges, disturbed anaphase-telophase cells, vagrants and stickiness in anaphase-telophase cells. All treatments of wastewater in April 2012, at S5 in July 2012, at S1 and S5 in November 2012, at S5 in February 2013, and at S1 in April 2013 induced CA when compared to the negative control. Some physicochemical parameters and heavy metals (Cd, Pb, and Cu) were also recorded in the samples examined.

  14. Oxygen radical-mediated mutagenic effect of asbestos on human lymphocytes: suppression by oxygen radical scavengers.

    PubMed

    Korkina, L G; Durnev, A D; Suslova, T B; Cheremisina, Z P; Daugel-Dauge, N O; Afanas'ev, I B

    1992-02-01

    The mutagenic effect of chrysotile asbestos fibers and zeolite and latex particles on human lymphocytes in whole blood has been studied. It was concluded that their mutagenic activities were mediated by oxygen radicals because they were inhibited by antioxidant enzymes (SOD and catalase) and oxygen radical scavengers (rutin, ascorbic acid, and bemitil). It was proposed that oxygen radicals were released by phagocytes activated upon exposure to mineral dusts and fibers. The study of lucigenin- and luminol-amplified chemiluminescence of peritoneal macrophages stimulated by chrysotile fibers and zeolite and latex particles has shown that their mutagenic action is probably mediated by different oxygen species, namely, by the iron-oxygen complexes (perferryl ions) plus hydrogen peroxide, hydrogen peroxide, and superoxide ion, respectively. From the oxygen radical scavengers studied, rutin was the most effective inhibitor of the mutagenic effect of mineral fibers and dusts.

  15. Genotoxic and mutagenic properties of Bauhinia platypetala extract, a traditional Brazilian medicinal plant.

    PubMed

    Santos, Francisco José Borges Dos; Moura, Dinara Jaqueline; Péres, Valéria Flores; Sperotto, Angelo Regis de Moura; Caramão, Elina Bastos; Cavalcante, Ana Amélia de Carvalho Melo; Saffi, Jenifer

    2012-12-18

    Bauhinia platypetala Burch. is a traditionally used Brazilian medicinal plant, although no evidence in the literature substantiates the safety of its use. The aim of this study was to investigate the safety of the ethanolic extract and the ethereal fraction of B. platypetala leaves. The identification of chemical compounds from the B. platypetala ethanolic extract and its ethereal fraction was performed by GC/MS and ESI-MS/MS. The plant's toxicological, cytotoxic, mutagenic and genotoxic properties were determined in Saccharomyces cerevisiae strains and V79 cell culture by survival assays and comet assay. The major compound identified in the B. platypetala ethanolic extract is palmitic acid, kaempferitirin and quercitrin, while the B. platypetala ethereal fraction was found to be rich in phytol, gamma-sitosterol and vitamin E. Moreover, the results indicated that the B. platypetala ethanolic extract has an anti-oxidative effect against H(2)O(2) in yeast. In addition, the B. platypetala ethanolic extract did not induce mutagenic effects on the S. cerevisiae N123 strain, but the ethereal fraction of B. platypetala at higher concentrations (250-500 μg/mL) induced cytotoxicity and mutagenicity. A slight cytotoxic effect was observed in mammalian V79 cells; however, both the B. platypetala ethanolic extract and its ethereal fraction were able to induce DNA strand breaks in V79 cells, as detected by the alkaline comet assay. The B. platypetala ethanolic extract has antioxidant action and showed absence of mutagenic effects in yeast S. cerevisiae. On the other hand B. platypetala ethereal fraction is mutagenic and does not show antioxidant activity in yeast. In mammalian cells B. platypetala ethanolic extract and it's ethereal fraction induce cyotoxic and genotoxic action. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. The effect of green tea and olive oil on the mutagenic activity of heterocyclic amines extracted from common food consumed in Saudi Arabia.

    PubMed

    Awney, Hala

    2011-05-01

    The effect of green tea (GT) and green tea with olive oil (GT+OL) as antioxidants on the formation and mutagenic activity of heterocyclic aromatic amines (HCAs) extracted from beef shawerma, grilled chicken and fried beef liver was examined. HCAs were extracted by blue rayon, analyzed as spiked and unspiked samples with high-performance liquid chromatography and its mutagenic response was assessed by Sallmonela typhimurium 100 in the Ames test. Surprisingly, GT and GT+OL augmented HCAs measured in beef shawerma and grilled chicken but total HCAs measured in GT+OL were less than GT treatment. Both treatments altered the HCA profile as imidazoquinoline type became the most abundant. In control and GT+OL fried beef liver no HCAs were detected, but Trp-P1 was detected in GT treatment. Generally, the mutagenic response of HCAs measured in GT+OL was less than GT in beef shawerma and grilled chicken. However, the mutagenic response of control and 2% GT+OL fried liver was negative. These data suggest that GT concentrations used in this study may induce free radical formation during the Millared reaction due to its pro-oxidative effect, which augmented the HCAs formed and its mutagenic response. In order to optimize both safety and quality of our diets, more need to be done to fully understand the risk of HCAs in food.

  17. Characterization of mutagen-activated cellular oncogenes that confer anchorage independence to human fibroblasts and tumorigenicity to NIH 3T3 cells: Sequence analysis of an enzymatically amplified mutant HRAS allele

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stevens, C.W.; Manoharan, T.H.; Fahl, W.E.

    1988-06-01

    Treatment of diploid human fibroblasts with an alkylating mutagen has been shown to induce stable, anchorage-independent cell populations at frequencies consistent with an activating mutation. After treatment of human foreskin fibroblasts with the mutagen benzo({alpha})pyrene ({plus minus})anti-7,8-dihydrodiol 9,10-epoxide and selection in soft agar, 17 anchorage-independent clones were isolated and expanded, and their cellular DNA was used to cotransfect NIH 3T3 cells along with pSV2neo. DNA from 11 of the 17 clones induced multiple NIH 3T3 cell tumors in recipient nude mice. Southern blot analyses showed the presence of human Alu repetitive sequences in all of the NIH 3T3 tumor cellmore » DNAs. Intact, human HRAS sequences were observed in 2 of the 11 tumor groups, whereas no hybridization was detected when human KRAS or NRAS probes were used. Slow-migrating ras p21 proteins, consistent with codon 12 mutations, were observed in the same two NIH 3T3 tumor cell groups that contained the human HRAS bands. Genomic DNA from one of these two human anchorage-independent cell populations (clone 21A) was used to enzymatically amplify a portion of exon 1 of the HRAS gene. The results demonstrate that exposure of normal human cells to a common environmental mutagen yields HRAS GC {yields} TA codon 12 transversions that have been commonly observed in human tumors.« less

  18. Survey of the mutagenicity of surface water, sediments, and drinking water from the Penobscot Indian Nation.

    PubMed

    Warren, Sarah H; Claxton, Larry D; Diliberto, Janet; Hughes, Thomas J; Swank, Adam; Kusnierz, Daniel H; Marshall, Valerie; DeMarini, David M

    2015-02-01

    U.S. Environmental Protection Agency (US EPA) Regional Applied Research Effort (RARE) projects address the effects of environmental pollutants in a particular region on the health of the population in that region. This report is part of a RARE project that addresses this for the Penobscot Indian Nation (PIN), Penobscot Island, Maine, U.S., where the Penobscot River has had fish advisories for many years due to high levels of mercury. We used the Salmonella mutagenicity assay with strains TA100, TA98, YG1041, and YG1042 with and without metabolic activation to assess the mutagenic potencies of organic extracts of the Penobscot River water and sediment, as well as drinking-water samples, all collected by the PIN Department of Natural Resources. The source water for the PIN drinking water is gravel-packed groundwater wells adjacent to the Penobscot River. Most samples of all extracts were either not mutagenic or had low to moderate mutagenic potencies. The average mutagenic potencies (revertants/L-equivalent) were 337 for the drinking-water extracts and 177 for the river-water extracts; the average mutagenic potency for the river-sediment extracts was 244 revertants(g-equivalent)(-1). This part of the RARE project showed that extracts of the Penobscot River water and sediments and Penobscot drinking water have little to no mutagenic activity that might be due to the classes of compounds that the Salmonella mutagenicity assay detects, such as polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs (nitroarenes), and aromatic amines. This study is the first to examine the mutagenicity of environmental samples from a tribal nation in the U.S. Published by Elsevier Ltd.

  19. Photodegradation of environmental mutagens by visible irradiation in the presence of xanthene dyes as photosensitizers.

    PubMed

    Odo, Junichi; Torimoto, Sei-ichi; Nakanishi, Suguru; Niitani, Tomoya; Aoki, Hiroyuki; Inoguchi, Masahiko; Yamasaki, Yu

    2012-01-01

    The photodegradation of environmental mutagens, such as 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAαC), and 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ), was investigated by visible irradiation in the presence of xanthene dyes as photosensitizers. Although the environmental mutagens themselves were very stable during visible irradiation under the conditions in this study, they were effectively photodegraded in the presence of the xanthene dyes (erythrosine, rose bengal, and phloxine). Moreover, photodegradation of the mutagens was further enhanced for xanthene dyes loaded onto a water-soluble diethylaminoethyl (DEAE)-dextran anion-exchanger via ionic interactions (xanthene-dyeDEX). Photodegradation was inhibited by O2 removal from the reaction solution. In ESR spin-trapping experiments using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a trapping reagent, signals characteristic of DMPO-•OH (hydroxyl radical) were observed in the presence of xanthene-dyeDEX. These results suggest that reactive oxygen species derived from O2, such as singlet molecular oxygen (•1O2) and/or •OH, were active participants in photodegradation of the mutagens in the presence of xanthene dyes or xanthene-dyeDEX.

  20. Application of effect-directed analysis to identify mutagenic nitrogenous disinfection by-products of advanced oxidation drinking water treatment.

    PubMed

    Vughs, D; Baken, K A; Kolkman, A; Martijn, A J; de Voogt, P

    2018-02-01

    Advanced oxidation processes are important barriers for organic micropollutants in (drinking) water treatment. It is however known that medium pressure UV/H 2 O 2 treatment may lead to mutagenicity in the Ames test, which is no longer present after granulated activated carbon (GAC) filtration. Many nitrogen-containing disinfection by-products (N-DBPs) result from the reaction of photolysis products of nitrate with (photolysis products of) natural organic material (NOM) during medium pressure UV treatment of water. Identification of the N-DBPs and the application of effect-directed analysis to combine chemical screening results with biological activity would provide more insight into the relation of specific N-DBPs with the observed mutagenicity and was the subject of this study. To this end, fractions of medium pressure UV-treated and untreated water extracts were prepared using preparative HPLC and tested using the Ames fluctuation test. In addition, high-resolution mass spectrometry was performed on all fractions to assess the presence of N-DBPs. Based on toxicity data and read across analysis, we could identify five N-DBPs that are potentially genotoxic and were present in relatively high concentrations in the fractions in which mutagenicity was observed. The results of this study offer opportunities to further evaluate the identity and potential health concern of N-DBPs formed during advanced oxidation UV drinking water treatment.

  1. Correlations of water quality parameters with mutagenicity of chlorinated drinking water samples.

    PubMed

    Schenck, Kathleen M; Sivaganesan, Mano; Rice, Glenn E

    2009-01-01

    Adverse health effects that may result from chronic exposure to mixtures of disinfection by-products (DBPs) present in drinking waters may be linked to both the types and concentrations of DBPs present. Depending on the characteristics of the source water and treatment processes used, both types and concentrations of DBPs found in drinking waters vary substantially. The composition of a drinking-water mixture also may change during distribution. This study evaluated the relationships between mutagenicity, using the Ames assay, and water quality parameters. The study included information on treatment, mutagenicity data, and water quality data for source waters, finished waters, and distribution samples collected from five full-scale drinking water treatment plants, which used chlorine exclusively for disinfection. Four of the plants used surface water sources and the fifth plant used groundwater. Correlations between mutagenicity and water quality parameters are presented. The highest correlation was observed between mutagenicity and the total organic halide concentrations in the treated samples.

  2. ASCORBIC ACID REDUCTION OF ACTIVE CHLORINE PRIOR TO DETERMINING AMES MUTAGENICITY OF CHLORINATED NATURAL ORGANIC MATTER (NOM)

    EPA Science Inventory

    Many potable water disinfection byproducts (DBPs) that result from the reaction of natural organic matter (NOM) with oxidizing chlorine are known or suspected to be carcinogenic and mutagenic. The Ames assay is routinely used to assess an overall level of mutagenicity for all com...

  3. COMPARATIVE MUTAGENICITY OF HALOMETHANES AND HALONITROMETHANES IN SALMONELLA TA100: STRUCTURE-ACTIVITY ANALYSIS AND MUTATION SPECTRA. (ERD)

    EPA Science Inventory

    Halonitromethanes (HNMs) are a recently identified class of disinfection by-products (DPBs) in drinking water that are mutagenic in Salmonella and potent inducers of DNA strand breaks in mammalian cells. Here we compared the mutagenic potencies of the HNMs to those of their halo...

  4. Urinary mutagenicity and N-acetylation phenotype in textile industry workers exposed to arylamines

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sinues, B.; Perez, J.; Bernal, M.L.

    1992-09-15

    Primary aromatic amines have been identified epidemiologically as human carcinogens. It has been suggested that the target organ affected by aromatic amines is dependent on the rate of metabolic activation. Epidemiological studies have shown an association between low acetyl transferase activity and bladder cancer risk. On this basis, our working hypothesis was that the slow acetylators could follow in a higher extent the metabolic pathway independent of N-acetylation, leading to the excretion of conjugates of electrophyles with glucuronic acid. The instability of these glucuronides could be responsible for the association between arylamine-induced bladder cancer and slow acetylator phenotype. A totalmore » of 153 individuals were included in this study: 70 exposed to arylamines (working in textile industry) and 83 nonexposed. The following parameters were determined in urine: mutagenic index in the absence of metabolic activation, S9; mutagenic index in the presence of S9; and the mutagenic index after incubation of the urine with beta-glucuronidase. All individuals were phenotyped according to their capacity of N-acetylation by using isoniazid as drug test. The results show that the mutagenic index after incubation of the urine with beta-glucuronidase is statistically higher in exposed subjects when compared with nonexposed individuals (P less than 0.001), this parameter being statistically higher among exposed subjects who were slow acetylators than among rapid metabolizers, independent of the fact that they were smokers or nonsmokers. There were no significant differences between groups for the mutagenicity in urine not incubated with beta-glucuronidase.« less

  5. Mutagens in urine of non-smoking and smoking workers in an aircraft tyre retreading plant. Skin exposure as a causal factor?

    PubMed

    Bos, R P; Kromhout, H; Ikink, H; de Haan, W; Koppejan, J; Theuws, J L

    1989-05-01

    In an aircraft type retreading plant environmental samples taken at several departments showed mutagenic properties. Thursday urine samples of non-smoking and smoking workers showed higher urinary mutagenicity than urine samples collected on Sundays, thus suggesting occupational exposure to mutagenic substances. A relation between urinary mutagenicity on Thursdays and skin contamination measured on Wednesdays was observed. The data suggest that intake through the skin plays an important role in the occupational exposure to mutagenic compounds of rubber workers.

  6. QSAR models to predict mutagenicity of acrylates, methacrylates and alpha,beta-unsaturated carbonyl compounds.

    PubMed

    Pérez-Garrido, Alfonso; Helguera, Aliuska Morales; Rodríguez, Francisco Girón; Cordeiro, M Natália D S

    2010-05-01

    The purpose of this study is to develop a quantitative structure-activity relationship (QSAR) model that can distinguish mutagenic from non-mutagenic species with alpha,beta-unsaturated carbonyl moiety using two endpoints for this activity - Ames test and mammalian cell gene mutation test - and also to gather information about the molecular features that most contribute to eliminate the mutagenic effects of these chemicals. Two data sets were used for modeling the two mutagenicity endpoints: (1) Ames test and (2) mammalian cells mutagenesis. The first one comprised 220 molecules, while the second one 48 substances, ranging from acrylates, methacrylates to alpha,beta-unsaturated carbonyl compounds. The QSAR models were developed by applying linear discriminant analysis (LDA) along with different sets of descriptors computed using the DRAGON software. For both endpoints, there was a concordance of 89% in the prediction and 97% confidentiality by combining the three models for the Ames test mutagenicity. We have also identified several structural alerts to assist the design of new monomers. These individual models and especially their combination are attractive from the point of view of molecular modeling and could be used for the prediction and design of new monomers that do not pose a human health risk. 2010 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  7. A reaction mechanism-based prediction of mutagenicity: α-halo carbonyl compounds adduct with DNA by SN2 reaction.

    PubMed

    Haranosono, Yu; Ueoka, Hiroki; Kito, Gakushi; Nemoto, Shingo; Kurata, Masaaki; Sakaki, Hideyuki

    2018-01-01

    Most of the α-halo carbonyl (AHC) compounds tend to be predicted as mutagenic by structure-activity relationship based on structural category only, because they have an alkyl halide structure as a structural alert of mutagenicity. However, some AHC compounds are not mutagenic. We hypothesized that AHC reacts with DNA by S N 2 reaction, and the reactivity relates to mutagenicity. As an index of S N 2 reactivity, we focused on molecular orbitals (MOs), as the direction and position of two molecules in collision are important in the S N 2 reaction. The MOs suitable for S N 2 reaction (SN2MOs) were selected by chemical-visual inspection based on the shape of the MO. We used the level gap and the energy gap between SN2MO and the lowest unoccupied molecular orbital as the descriptors of S N 2 reactivity. As the results, S N 2 reactivity related to mutagenicity and we were able to predict mutagenicity of 20 AHC compounds with 95.0% concordance. It was suggested that S N 2 reaction is a reaction mechanism of AHC compounds and DNA in the mutagenic process. The method allows for discrimination among structurally similar compounds by combination with quantitative structure-activity relationships. The combination approach is expected to be useful for the mutagenic assessment of pharmaceutical impurities.

  8. Mutagenic interactions between X-rays and two promutagens, o-phenylenediamine and N-nitrosodimethylamine, in the stamen hairs of Tradescantia clone BNL 4430.

    PubMed

    Xiao, L Z; Ichikawa, S

    1998-03-16

    Mutagenic interactions between X-rays and two promutagens, o-phenylenediamine (PDA) and N-nitrosodimethylamine (DMN), were studied in the stamen hairs of Tradescantia clone BNL 4430, a blue/pink heterozygote. The young inflorescence-bearing shoots with roots of this clone cultivated in a nutrient solution circulating growth chamber were used as tester plants. After determining dose-response curves for X-rays. PDA and DMN, combined treatments with PDA or DMN and X-rays were conducted, exposing acutely to X-rays 20 h before starting, at the midpoint of, or 20 h after completing the PDA or DMN treatments for 4 h. Clear synergistic effects in inducing somatic pink mutations were detected when X-rays were irradiated before the PDA or DMN treatments, resembling those confirmed earlier between maleic hydrazide (MH) and X-rays. On the contrary, clear antagonistic effects were observed when X-rays were given after the PDA or DMN treatments, also resembling those between MH and X-rays. When X-rayed at the midpoint of the PDA or DMN treatments, merely additive and synergistic effects were observed, respectively, differing from the antagonistic effects between MH and X-rays. The mutagenic synergisms detected were considered to be the results of interactions between DNA strand breaks (and the resultant chromosome breaks) induced by X-rays and those by PDA or DMN, whereas the mutagenic antagonisms observed were presumed to be due to X-ray-caused inhibition of the activation of PDA and DMN in the stamen-hair cells. The time periods required for penetrations into floral tissues and/or activations into mutagens seem different among PDA, DMN and MH. Copyright 1998 Elsevier Science B.V.

  9. Urinary 1-hydroxypyrene and mutagenicity in bus drivers and mail carriers exposed to urban air pollution in Denmark.

    PubMed

    Hansen, Ase Marie; Wallin, Håkan; Binderup, Mona Lise; Dybdahl, Marianne; Autrup, Herman; Loft, Steffen; Knudsen, Lisbeth Ehlert

    2004-01-10

    Previous studies in Denmark have shown that bus drivers and tramway employees were at an increased risk for developing several types of cancer and that bus drives from central Copenhagen have high levels of biomarkers of DNA damage. The present study evaluates 1-hydroxypyrene concentrations and mutagenic activity in urine as biomarkers of exposure in non-smoking bus drivers in city and rural areas on a work day and a day off and in non-smoking mail carriers working outdoors (in the streets) and indoors (in the office). Twenty-four hour urine samples were collected on a working day and a day off from 60 non-smoking bus drivers in city and rural areas and from 88 non-smoking mail carriers working outdoors (in the streets) and indoors (in the office). The concentration of 1-hydroxypyrene was measured by means of HPLC and the mutagenic activity was assessed by the Ames assay with Salmonella tester strain YG1021 and S9 mix. The N-acetyltransferase (NAT2) phenotype was used as a biomarker for susceptibility to mutagenic/carcinogenic compounds. Bus drivers excreted more 1-hydroxypyrene in urine than did mail carriers. The differences were slightly smaller when NAT2 phenotype, cooking at home, exposure to vehicle exhaust, and performing physical exercise after work were included. The NAT2 slow acetylators had 29% (1.29 [CI: 1.15-1.98]) higher 1-hydroxypyrene concentrations in urine than the fast acetylators. Male bus drivers had 0.92 revertants/mol creatinine [CI: 0.37-1.47] and female bus drivers 1.90 revertants/mol creatinine [CI: 1.01-2.79] higher mutagenic activity in urine than mail carriers. The present study indicates that bus drivers are more exposed to polycyclic aromatic hydrocarbons (PAH) and mutagens than mail carriers. Mail carriers who worked outdoors had higher urinary concentration of 1-hydroxypyrene, a marker of exposure to PAH, than those working indoors. The individual levels of urinary mutagenic activity were not correlated to excretion of 1

  10. Mutagenicity of aerosols from the oxidative thermal decomposition of rigid polyurethane foam.

    PubMed

    Zitting, A; Falck, K; Skyttä, E

    1980-01-01

    The aerosol fraction of the oxidative thermal decomposition products (700 degrees C) of rigid polyurethane foam was collected on glass fiber filters and fractionated into either-soluble neutral, acidic, and basic fractions and water-soluble compounds. The fractions showed mutagenic activity in a bacterial fluctuation test with Salmonella typhimurium TA98 or Escherichia coli CM891 as the tester strains. All the fractions induced mutations in both strains after metabolic activation with rat liver S-9 mix. The basic and the water-soluble fractions were mutagenic for S. typhimurium TA 98 even without activation. Thin-layer chromatography showed the presence of several primary aromatic amines in the aerosol. Polycyclic aromatic hydrocarbons were not detected by glass capillary gas chromatogaphy.

  11. Excretion of 3-hydroxy-benzo(a)pyrene and mutagenicity in rat urine after exposure to benzo(a)pyrene.

    PubMed

    Jongeneelen, F J; Leijdekkers, C M; Bos, R P; Theuws, J L; Henderson, P T

    1985-10-01

    3-hydroxy-benzo(a)pyrene (3-OH-B(a)P) and mutagenic activity in rat urine were determined after the oral administration of benzo(a)pyrene given in three repeated doses of 10, 20 and 50 mumol kg-1. The procedure for the determination of 3-OH-B(a)P consisted of enzymic hydrolysis, separation and HPLC-analysis. The mutagenic activity of concentrated urine samples was assayed with the Salmonella typhimurium strain TA98 in the presence of S9 mix and beta-glucuronidase. The urinary excretion of 3-OH-B(a)P and mutagens showed a correlation and both increased dose-dependently during the sampling period of 6 days. Data indicated that 3-OH-B(a)P can be regarded as a reliable representative of all urinary (pre)-mutagens derived from benzo(a)pyrene and exposure of rats to benzo(a)pyrene could be detected with greater sensitivity by the HPLC assay of 3-OH-B(a)P than with the non-specific mutagenicity assay.

  12. Bacterial and human cell mutagenicity study of some C18H10 cyclopenta-fused polycyclic aromatic hydrocarbons associated with fossil fuels combustion.

    PubMed Central

    Lafleur, A L; Longwell, J P; Marr, J A; Monchamp, P A; Plummer, E F; Thilly, W G; Mulder, P P; Boere, B B; Cornelisse, J; Lugtenburg, J

    1993-01-01

    A number of isomeric C18H10 polycyclic aromatic hydrocarbons (PAHs), thought to be primarily cyclopenta-fused PAHs, are produced during the combustion and pyrolysis of fossil fuels. To determine the importance of their contributions to the total mutagenic activity of combustion and pyrolysis samples in which they are found, we characterized reference quantities of four C18H10 CP-PAHs: benzo[ghi]fluoranthene (BF), cyclopenta[cd]pyrene (CPP), cyclopent[hi]acephenanthrylene (CPAP), and cyclopent[hi]aceanthrylene (CPAA). Synthesis of CPAA and CPAP is described. The availability of reference samples of these isomers also proved to be an essential aid in the identification of the C18H10 species often found in combustion and pyrolysis samples. Chemical analysis of selected combustion and pyrolysis samples showed that CPP was generally the most abundant C18H10 isomer, followed by CPAP and BF. CPAA was detected only in pyrolysis products from pure PAHs. We tested the four C18H10 PAHs for mutagenicity in a forward mutation assay using S. typhimurium. CPP, BF, and CPAA were roughly twice as mutagenic as benzo[a]pyrene (BaP), whereas CPAP was only slightly active. These PAHs were also tested for mutagenic activity in human cells. In this assay, CPP and CPAA were strongly mutagenic but less active than BaP, whereas CPAP and BF were inactive at the dose levels tested. Also, the bacterial and human cell mutagenicity of CPAA and CPAP were compared with the mutagenicity of their monocyclopenta-fused analogs, aceanthrylene and acephenanthyrlene. Although the mutagenicities of CPAP and acephenanthrylene are similar, the mutagenic activity of CPAA is an order of magnitude greater than that of aceanthyrlene. PMID:8354201

  13. Effect aquadest-extracted Gloriosa superba seed as mutagen on morphology of Artemisia annua

    NASA Astrophysics Data System (ADS)

    Rahmawati, S. I.; Susilowati, A.; Yunus, A.; Widyastuti, Y.

    2018-03-01

    Gloriosa superba is a plant that contains colchicine in all parts of organs, especially in the seeds. Its extract is as a mutagen to produce plants with polyploid cells. Artemisia annua is a plant that produces active ingredients artemisinin as malarial drugs, hemorrhoids therapy, aromatherapy, antiviral, anticancer, and anti-bacterial. The aims of this research was to determine the effect aquadest-extracted Gloriosa superba seed as a mutagen to Artemisia annua morphology. Extraction of Gloriosa superba seeds obtained from Sukoharjo using maceration method with aquadest solvent (1: 1). The extracts were diluted (0, 25, 50, 75 and 100%) for Artemisia annua sprinkling with different times (0, 30, 60 and 90 minutes). Observations of morphology Artemisia annua included height, stem circumference, number of branches, number of leaves, leaf width and leaf length. The treatments did not affect plant morphology observation included height, stem circumference, number of branches, number of leaves, leaf width, and leaf length. The EB treatment (100%, 30 minutes) was higher (120 cm) than other. In all treatments stem circumference about 2.5 cm, number of branches ranged between 40-50, leaves width ranged 9-16c m, and leaf length ranged 8-15 cm.

  14. Composition, toxicity, and mutagenicity of particulate and semivolatile emissions from heavy-duty compressed natural gas-powered vehicles.

    PubMed

    Seagrave, JeanClare; Gigliotti, Andrew; McDonald, Jacob D; Seilkop, Steven K; Whitney, Kevin A; Zielinska, Barbara; Mauderly, Joe L

    2005-09-01

    Particulate matter (PM) and vapor-phase semivolatile organic compounds (SVOC) were collected from three buses fueled by compressed natural gas. The bus engines included a well-functioning, conventional engine; a "high emitter" engine; and a new technology engine with an oxidation catalyst. Chemical analysis of the emissions showed differences among these samples, with the high emitter sample containing markers of engine oil constituents. PM + SVOC samples were also collected for mutagenicity and toxicity testing. Extraction efficiencies from the collection media were lower than for similarly collected samples from gasoline or diesel vehicles. Responses to the recovered samples were compared on the basis of exhaust volume, to incorporate the emission rates into the potency factors. Mutagenicity was assessed by Salmonella reverse mutation assay. Mutagenicity was greatest for the high emitter sample and lowest for the new technology sample. Metabolic activation reduced mutagenicity in strain TA100, but not TA98. Toxicity, including inflammation, cytotoxicity, and parenchymal changes, was assessed 24 h after intratracheal instillation into rat lungs. Lung responses were generally mild, with little difference between the responses to equivalent volumes of emissions from the normal emitter and the new technology, but greater responses for the high emitter. These emission sample potencies are further compared on the basis of recovered mass with previously reported samples from normal and high-emitter gasoline and diesel vehicles. While mutagenic potencies for the CNG emission samples were similar to the range observed in the gasoline and diesel emission samples, lung toxicity potency factors were generally lower than those for the gasoline and diesel samples.

  15. On the mutagenicity of homologous recombination and double-strand break repair in bacteriophage.

    PubMed

    Shcherbakov, Victor P; Plugina, Lidiya; Shcherbakova, Tamara; Sizova, Svetlana; Kudryashova, Elena

    2011-01-02

    The double-strand break (DSB) repair via homologous recombination is generally construed as a high-fidelity process. However, some molecular genetic observations show that the recombination and the recombinational DSB repair may be mutagenic and even highly mutagenic. Here we developed an effective and precise method for studying the fidelity of DSB repair in vivo by combining DSBs produced site-specifically by the SegC endonuclease with the famous advantages of the recombination analysis of bacteriophage T4 rII mutants. The method is based on the comparison of the rate of reversion of rII mutation in the presence and in the absence of a DSB repair event initiated in the proximity of the mutation. We observed that DSB repair may moderately (up to 6-fold) increase the apparent reversion frequency, the effect of being dependent on the mutation structure. We also studied the effect of the T4 recombinase deficiency (amber mutation in the uvsX gene) on the fidelity of DSB repair. We observed that DSBs are still repaired via homologous recombination in the uvsX mutants, and the apparent fidelity of this repair is higher than that seen in the wild-type background. The mutator effect of the DSB repair may look unexpected given that most of the normal DNA synthesis in bacteriophage T4 is performed via a recombination-dependent replication (RDR) pathway, which is thought to be indistinguishable from DSB repair. There are three possible explanations for the observed mutagenicity of DSB repair: (1) the origin-dependent (early) DNA replication may be more accurate than the RDR; (2) the step of replication initiation may be more mutagenic than the process of elongation; and (3) the apparent mutagenicity may just reflect some non-randomness in the pool of replicating DNA, i.e., preferential replication of the sequences already involved in replication. We discuss the DSB repair pathway in the absence of UvsX recombinase. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. 2,3,7,8 tetrachlorodibenzodioxin in fish from the Pigeon river of Eastern Tennessee: Its toxicity and mutagenicity as revealed by the Ames Salmonella Assay

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Blevins, R.D.

    1990-04-01

    Levels of 2,3,7,8 tetrachlorodibenzodioxin (TCDD)were determined in both striated muscle (fillets) and whole body extracts of fish specimens harvested during a two year period (1987-1989) from the Pigeon River (between Hartford and Newport) of Eastern Tennessee. Whole body (wet weight) fish extract levels as high as 117 {mu}g/kg body weight and composite fish fillet (wet weight) extract levels as high 87 {mu}g/kg fillet weight were observed. Pure TCDD was found to be highly toxic to the Salmonella typhimurium strains TA97, TA98, TA100, TA102 and TA1535 at TCDD dosages which exceeded 825 ng/ml in the top agar of the Ames Salmonellamore » assay. An 825 ng/ml TCDD dosage was not mutagenic to any of the tested Salmonella strains, (both with and without metabolic activation (S9) mix). However, when both acidic and alcohol fish extracts from the Pigeon River were tested for mutagenicity, several of the fish extracts were found to be mutagenic to Salmonella strains TA97, TA98, and TA100 (having mutagenic ratios which greatly exceeded the 2.5 {times} spontaneous ratio). These mutagenic extracts also demonstrated mutagenic dose-response curves. Other chemicals within the extracts as well as synergistic effects may account for the mutagenicity.« less

  17. Atypical Role for PhoU in Mutagenic Break Repair under Stress in Escherichia coli

    PubMed Central

    Aponyi, Ildiko; Vera Cruz, Diana; Ray, Mellanie P.; Rosenberg, Susan M.

    2015-01-01

    Mechanisms of mutagenesis activated by stress responses drive pathogen/host adaptation, antibiotic and anti-fungal-drug resistance, and perhaps much of evolution generally. In Escherichia coli, repair of double-strand breaks (DSBs) by homologous recombination is high fidelity in unstressed cells, but switches to a mutagenic mode using error-prone DNA polymerases when the both the SOS and general (σS) stress responses are activated. Additionally, the σE response promotes spontaneous DNA breakage that leads to mutagenic break repair (MBR). We identified the regulatory protein PhoU in a genetic screen for functions required for MBR. PhoU negatively regulates the phosphate-transport and utilization (Pho) regulon when phosphate is in excess, including the PstB and PstC subunits of the phosphate-specific ABC transporter PstSCAB. Here, we characterize the PhoU mutation-promoting role. First, some mutations that affect phosphate transport and Pho transcriptional regulation decrease mutagenesis. Second, the mutagenesis and regulon-expression phenotypes do not correspond, revealing an apparent new function(s) for PhoU. Third, the PhoU mutagenic role is not via activation of the σS, SOS or σE responses, because mutations (or DSBs) that restore mutagenesis to cells defective in these stress responses do not restore mutagenesis to phoU cells. Fourth, the mutagenesis defect in phoU-mutant cells is partially restored by deletion of arcA, a gene normally repressed by PhoU, implying that a gene(s) repressed by ArcA promotes mutagenic break repair. The data show a new role for PhoU in regulation, and a new regulatory branch of the stress-response signaling web that activates mutagenic break repair in E. coli. PMID:25961709

  18. Nonmutagenicity of betel leaf and its antimutagenic action against environmental mutagens.

    PubMed

    Nagabhushan, M; Amonkar, A J; D'Souza, A V; Bhide, S V

    1987-01-01

    Betel leaf (Piper betel) water and acetone extract are nonmutagenic in S. typhimurium strains with and without S9 mix. Both the extracts suppress the mutagenicity of betel quid mutagens in a dose dependent manner. Moreover both the extracts of betel leaf reduce the mutagenicity of benzo(a)pyrene and dimethylbenzanthracene. Acetone extract is more potent than water extract in inhibiting mutagenicity of environmental mutagens.

  19. DNA replication after mutagenic treatment in Hordeum vulgare.

    PubMed

    Kwasniewska, Jolanta; Kus, Arita; Swoboda, Monika; Braszewska-Zalewska, Agnieszka

    2016-12-01

    The temporal and spatial properties of DNA replication in plants related to DNA damage and mutagenesis is poorly understood. Experiments were carried out to explore the relationships between DNA replication, chromatin structure and DNA damage in nuclei from barley root tips. We quantitavely analysed the topological organisation of replication foci using pulse EdU labelling during the S phase and its relationship with the DNA damage induced by mutagenic treatment with maleic hydrazide (MH), nitroso-N-methyl-urea (MNU) and gamma ray. Treatment with mutagens did not change the characteristic S-phase patterns in the nuclei; however, the frequencies of the S-phase-labelled cells after treatment differed from those observed in the control cells. The analyses of DNA replication in barley nuclei were extended to the micronuclei induced by mutagens. Replication in the chromatin of the micronuclei was rare. The results of simultanous TUNEL reaction to identify cells with DNA strand breaks and the labelling of the S-phase cells with EdU revealed the possibility of DNA replication occurring in damaged nuclei. For the first time, the intensity of EdU fluorescence to study the rate of DNA replication was analysed. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Genotoxic potentials of lifestyles assessed by urinary mutagenicity.

    PubMed

    Mure, K; Morimoto, K

    1994-09-01

    The relationships between lifestyles and urinary mutagenicity were investigated by using blue rayon extraction from 33 healthy male workers' urine. Subjects were classified into three groups, as "good", "moderate", and "poor" according to their responses on a questionnaire regarding eight health practices (cigarette smoking, alcohol consumption, eating breakfast, hours of sleep, hours of work, physical exercise, caring about nutritional balance, mental stress). The better lifestyle groups exhibited the lower mutagenicity. Subjects in a "good" group showed significantly lower urinary mutagenicity than those both in a "moderate" (p < 0.05) and a "poor" (p < 0.05) groups at fraction number 1 to 3 that were given after ingesting fried beef. These tendencies also found at fraction number 8 to 9 that were given after smoking, although not significant. The lifestyles were significantly associated with the urinary mutagenicity, and the results suggested that not only particular lifestyle factor but also some combinations with smoking significantly enhanced with the urinary mutagenicity.

  1. REPRODUCTIVE EFFECTS ASSESSMENT GROUP'S REVIEW OF THE MUTAGENICITY OF VINYLIDENE CHLORIDE

    EPA Science Inventory

    A large number of studies indicate that vinylidene chloride is mutagenic to bacteria and that this activity is largely dependent on microsomal activation. Vinylidene chloride was reported to produce positive results for gene reversion and conversion in yeast, which was also depen...

  2. The effects of pre-incubation period and norharman on the mutagenic potency of 4-dimethylaminoazobenzene and 3'-methyl-4-dimethylaminoazobenzene in S. typhimurium.

    PubMed

    Lefevre, P A; Ashby, J

    1981-01-01

    The effects of the co-mutagen norharman on the mutagenicity of the rodent liver carcinogens 4-dimethyl-aminoazobenzene (DAB) and 3'-methyl-4-dimethyl-aminoazobenzene (3'-MeDAB) have been evaluated using the Ames Salmonella mutation assay. A period of pre-incubation was found to be necessary in order to detect DAB as a mutagen and to increase the initially weak response observed for 3'MeDAB; maximum responses were seen after 1 h pre-incubation in each case. The co-mutagenic properties of norharman were at their maximum for both azo-dyes in the direct plate-incorporation assay. Pre-incubation of either compound with norharman for increasing periods of time resulted in a decrease in potentiation, until after 1 h, an inhibition of mutagenicity was observed.

  3. Mutagen Synergy: Hypermutability Generated by Specific Pairs of Base Analogs

    PubMed Central

    Ang, Jocelyn; Song, Lisa Yun; D'Souza, Sara; Hong, Irene L.; Luhar, Rohan; Yung, Madeline

    2016-01-01

    ABSTRACT We tested pairwise combinations of classical base analog mutagens in Escherichia coli to study possible mutagen synergies. We examined the cytidine analogs zebularine (ZEB) and 5-azacytidine (5AZ), the adenine analog 2-aminopurine (2AP), and the uridine/thymidine analog 5-bromodeoxyuridine (5BrdU). We detected a striking synergy with the 2AP plus ZEB combination, resulting in hypermutability, a 35-fold increase in mutation frequency (to 53,000 × 10−8) in the rpoB gene over that with either mutagen alone. A weak synergy was also detected with 2AP plus 5AZ and with 5BrdU plus ZEB. The pairing of 2AP and 5BrdU resulted in suppression, lowering the mutation frequency of 5BrdU alone by 6.5-fold. Sequencing the mutations from the 2AP plus ZEB combination showed the predominance of two new hot spots for A·T→G·C transitions that are not well represented in either single mutagen spectrum, and one of which is not found even in the spectrum of a mismatch repair-deficient strain. The strong synergy between 2AP and ZEB could be explained by changes in the dinucleoside triphosphate (dNTP) pools. IMPORTANCE Although mutagens have been widely studied, the mutagenic effects of combinations of mutagens have not been fully researched. Here, we show that certain pairwise combinations of base analog mutagens display synergy or suppression. In particular, the combination of 2-aminopurine and zebularine, analogs of adenine and cytidine, respectively, shows a 35-fold increased mutation frequency compared with that of either mutagen alone. Understanding the mechanism of synergy can lead to increased understanding of mutagenic processes. As combinations of base analogs are used in certain chemotherapy regimens, including those involving ZEB and 5AZ, these results indicate that testing the mutagenicity of all drug combinations is prudent. PMID:27457718

  4. Mutagenicity of urine from individuals exposed to LPG combustion products.

    PubMed

    Yin, X J; Liu, J Z; Kong, X H; Chu, J H; Wang, H; Xiao, Z X

    1998-09-01

    The mutagenicity of urine from individuals exposed to the combustion products of liquefied petroleum gas (LPG) was detected with Salmonella typhimurium TA98 and its newly developed derivatives YG1021 (nitroreductase overproducing) and YG1024 (O-acetyltransferase overproducing). The detection showed significantly increased mutagenicity for the two YG strains and increased positive rates for all three strains in the presence of both rat liver S9 and beta-glucuronidase. Further analysis demonstrated that urine samples taken from smoking and non-smoking exposed individuals exhibited significantly higher mutagenic potency (revertants/10 microliters urine concentrate) than their corresponding controls. These results indicate that the increased urine mutagenicity is caused by the exposure to LPG combustion products or smoking. The mutagenic potency of urine samples of all exposed individuals tested with YG1024 was found to be about 7 times higher than with TA98. The difference in mutagenic potency was smaller for the same samples when comparison was made between YG1021 and TA98. This suggests that the mutagenic compounds present in the urine samples contain mainly aromatic compounds as glucuronide conjugates. Our results demonstrate that YG1024 is more sensitive than TA98 in detecting the mutagenicity of these samples. In addition, no significant difference in the mutagenic potency between the 'pure' exposed (non-smokers') and the 'pure' smokers' (unexposed) samples was found in all three tester strains. This might mean that the exposure extent of mutagens/carcinogens in LPG combustion products for exposed individuals roughly corresponds to the smoking level of smokers who smoke 20-40 cigarettes per day. Furthermore, the results also suggest that synergism might exist in the mutagenic effects of exposure to LPG combustion products and cigarette smoking.

  5. Metabolism and mutagenicity of halogenated olefins--a comparison of structure and activity.

    PubMed Central

    Henschler, D

    1977-01-01

    Chlorinated ethylenes are metabolized in mammals, as a first step, to epoxides. The fate of these electrophilic intermediates may be reaction with nucleophiles (alkylation), hydrolysis, or intramolecular rearrangement. The latter reaction has been studied in the whole series of chlorinated epoxiethanes. The rearrangement products found were: acyl chlorides (tetrachloro-, trichloro-, and 1,1-dichloroethylenes), or chlorinated aldehydes (1,2-dichloroethylenes, cis- and trans-, vinyl chloride). The metabolities found in vivo are identical with, or further derivatives of these rearrangment products, with one important exception: trichloroethylene. With this compound, in vivo rearrangement yields chloral exclusively. The mechanism of the different rearrangement has been identified as a Lewis acid catalysis. All chlorinated ethylenes have been investigated in a tissue-mediated mutagenicity testing system. The prominent molecular feature of those with mutagenic effects (trichloro-, 1,1-dichloro-, and monochloroethylene) is unsymmetric chlorine substitution which renders the epoxides unstable, whereas symmetric substitution confers relative stability and nonmutagenic property. PMID:348459

  6. Mutagenicity testing of the antiparasitic drug entizol (polfa) in the detection system of Salmonella typhimurium mutants.

    PubMed

    Dobiás, L

    1980-02-01

    The mutagenic activity was tested of a clinically used drug Entizol (Polfa) which contains metronidazole as an active substance. The mutagenicity of the compound was detected for Salmonella typhimurium indicator strains TA100, TA1535, TA1950, and TA1538 in tests in vitro without metabolic activation at the concentration range of 180 to 1600 microgram per plate. Metabolic conversion of the preparation studied in vivo gave rise to mutagenic metabolites detectable in the blood of mice after both intraperitoneal and per-oral application. The presence of the products of drug metabolism in the blood of experimental animals was tested at 1-40 h intervals after application. Blood samples of mice treated intraperitoneally with single doses of 1470 and 35 mg/kg were tested in strains TA100 and TA98. There were differences in the times of occurrence of mutagenic metabolites. The development of two mutagenicity maxima, detected in the blood withdrawn within the interval of 60-120 min (Rt/Rc 3.1) and 19 h (Rt/Rc 24.8) after the application of a dose of 1470 mg/kg in the strain TA100, is characteristic. The mutagenic effect of the blood of animals treated with a dose of 35 mg/kg, which approximately corresponds to standard therapeutic values, also had an analogous character. The highest mutagenic effect was detected in blood samples withdrawn 19 h after application (Rt/Rc 15.8). The frameshift mutation-detecting strain TA98 reverted at a lower frequency (about 5 times) under the above conditions, but only during analysis of the blood samples of animals treated with a dose of 1470 mg/kg. These results indicate that, for assessing the mutagenicity of 5-nitroimidazole compounds and their metabolites in blood, it is necessary to analyse blood samples withdrawn at least up to 24 h after application of the compound. This relationship was not proved to exist between the frequencies of induced revertants during the testing of blood withdrawn within 1-24 h after single per

  7. Is Tobacco Smoke a Germ-Cell Mutagen?

    EPA Science Inventory

    Although no international organization exists to declare whether an agent is a germ-cell mutagen, tobacco smoke may be a human germ-cell mutagen. In the mouse, tobacco smoke induces a significant increase in the mutation frequency at an expanded simple tandem repeat (ESTR) locus....

  8. Carcinogenicity and mutagenicity of chromium.

    PubMed

    Léonard, A; Lauwerys, R R

    1980-11-01

    Occupational exposure represents the main source of human contamination by chromium. For non-occupationally exposed people the major environmental exposure to chromium occurs as a consequence of its presence in food. Chromium must be considered as an essential element. Its deficiency impairs glucose metabolism. Trivalent chromium salts are poorly absorbed through the gastro-intestinal and respiratory tracts because they do not cross membranes easily. Hexavalent chromium can be absorbed by the oral and pulmonary routes and probably also through the skin. After its absorption, hexavalent chromium is rapidly reduced to the trivalent form which is probably the only form to be found in biological material. Epidemiological studies have shown that some chromium salts (mainly the slightly soluble hexavalent salts) are carcinogens. Lung cancers have, indeed, often been reported among workers in chromate-producing industry and, to a lesser extent, in workers from the chrome-pigment industry. The first attempts to produce cancers in experimental animals by inhalation or parenteral introduction gave negative or equivocal results but, from 1960, positive results have been obtained with various chromium compounds. As for the carcinogenic activity, the mutagenicity of chromium has mainly been found with hexavalent salts. In the majority of assay systems used, trivalent chromium appears inactive. It can be considered as evident, however, that the ultimate mutagen which binds to the genetic material is the trivalent form produced intracellularly from hexavalent chromium, the apparent lack of activity of the trivalent form being due to its poor cellular uptake.

  9. Evaluation of Anti-HIV-1 Mutagenic Nucleoside Analogues*

    PubMed Central

    Vivet-Boudou, Valérie; Isel, Catherine; El Safadi, Yazan; Smyth, Redmond P.; Laumond, Géraldine; Moog, Christiane; Paillart, Jean-Christophe; Marquet, Roland

    2015-01-01

    Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold of viability. Their existence as quasi-species has pioneered the concept of “lethal mutagenesis” that prompted us to synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent with an accumulation of deleterious mutations in the HIV-1 genome. However, testing all potentially mutagenic compounds in cell-based assays is tedious and costly. Here, we describe two simple in vitro biophysical/biochemical assays that allow prediction of the mutagenic potential of deoxyribonucleoside analogues. The first assay compares the thermal stabilities of matched and mismatched base pairs in DNA duplexes containing or not the nucleoside analogues as follows. A promising candidate should display a small destabilization of the matched base pair compared with the natural nucleoside and the smallest gap possible between the stabilities of the matched and mismatched base pairs. From this assay, we predicted that two of our compounds, 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine, should be mutagenic. The second in vitro reverse transcription assay assesses DNA synthesis opposite nucleoside analogues inserted into a template strand and subsequent extension of the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine are predicted to be efficient mutagens. The predictive potential of our fast and easy first line screens was confirmed by detailed analysis of the mutation spectrum induced by the compounds in cell culture because only compounds 5-hydroxymethyl-2′-deoxyuridine and 5-hydroxymethyl-2′-deoxycytidine were found to increase the mutation frequency by 3.1- and 3.4-fold, respectively. PMID:25398876

  10. Evaluation of anti-HIV-1 mutagenic nucleoside analogues.

    PubMed

    Vivet-Boudou, Valérie; Isel, Catherine; El Safadi, Yazan; Smyth, Redmond P; Laumond, Géraldine; Moog, Christiane; Paillart, Jean-Christophe; Marquet, Roland

    2015-01-02

    Because of their high mutation rates, RNA viruses and retroviruses replicate close to the threshold of viability. Their existence as quasi-species has pioneered the concept of "lethal mutagenesis" that prompted us to synthesize pyrimidine nucleoside analogues with antiviral activity in cell culture consistent with an accumulation of deleterious mutations in the HIV-1 genome. However, testing all potentially mutagenic compounds in cell-based assays is tedious and costly. Here, we describe two simple in vitro biophysical/biochemical assays that allow prediction of the mutagenic potential of deoxyribonucleoside analogues. The first assay compares the thermal stabilities of matched and mismatched base pairs in DNA duplexes containing or not the nucleoside analogues as follows. A promising candidate should display a small destabilization of the matched base pair compared with the natural nucleoside and the smallest gap possible between the stabilities of the matched and mismatched base pairs. From this assay, we predicted that two of our compounds, 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine, should be mutagenic. The second in vitro reverse transcription assay assesses DNA synthesis opposite nucleoside analogues inserted into a template strand and subsequent extension of the newly synthesized base pairs. Once again, only 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine are predicted to be efficient mutagens. The predictive potential of our fast and easy first line screens was confirmed by detailed analysis of the mutation spectrum induced by the compounds in cell culture because only compounds 5-hydroxymethyl-2'-deoxyuridine and 5-hydroxymethyl-2'-deoxycytidine were found to increase the mutation frequency by 3.1- and 3.4-fold, respectively. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Evaluation of the cytotoxicity, mutagenicity and antimutagenicity of emerging edible plants.

    PubMed

    Yen, G C; Chen, H Y; Peng, H H

    2001-11-01

    This study evaluates the toxic, mutagenic and antimutagenic effects of emerging edible plants that are consumed as new leafy vegetables in Taiwan. Among eight plant extracts, only the extracts of Sol (Solanum nigrum L.) showed cytotoxicity to Salmonella typhimurium TA100 in the absence of S9 mix. The toxicity of extracts from different parts of the Sol plant, such as leaf and stem, immature fruit and mature fruit, towards S. typhimurium TA100 and human lymphocytes was also assayed. The immature fruit extracts of Sol exhibited strong cytotoxicity with dose dependence and induced significant DNA damage in human lymphocytes based on the comet assay. However, no mutagenicity was found in eight plant extracts to TA98 or TA100 either with or without the S9 mixture. Sol and Sec [Sechium edule (Jacq.) Swartz] extracts showed the strongest inhibitory effect towards the mutagenicity of 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) in S. typhimurium TA98 and TA100; the ID(50) was less then 1 mg/plate. Cra [Crassocephalum creidioides (Benth.) S. Moore] extracts also expressed moderate antimutagenic activities towards IQ and benzo[a]pyrene (B[a]P) either in TA98 or in TA100; the ID(50) was 1.63-2.41 mg/plate. The extracts from Bas (Basella alba L.), Bou (Boussingaultia gracilis Miers var. pseudobaselloides Bailey), Cen (Centella asiatica L. Urban), Cor (Corchorus olitorius L.) and Por (Portulaca oleracea L.) showed weak to moderate inhibition of mutagenicity of IQ. However, the potential antimutagenicity of these plant extracts towards B[a]P was weaker than that towards IQ. For a direct mutagen, 4-nitroquinoline-N-oxide (NQNO), only the Sol extracts showed strong inhibitory effects in the TA100 system. The antimutagenic activity of water extracts of Sec was partly reduced by heating at 100 degrees C for 20 min. The heat-stable antimutagens in Sec extracts could be produced in the plant extract preparation process. Fractions with molecular weights above 30,000 showed the

  12. TOPICAL REVIEW: MUTAGENICITY AND CARCINOGENICITY OF AIR

    EPA Science Inventory

    Although both outdoor and indoor airs provide exposure to mutagens and carcinogens, this review shows that the level of hazard is highly variable. Outdoor air was first shown to be carcinogenic in 1942 and mutagenic in 1975; and studies examining the genotoxicity of indoor air so...

  13. Toxicological and mutagenic analysis of Artemisia dracunculus (tarragon) extract.

    PubMed

    Kalantari, Heibatullah; Galehdari, Hamid; Zaree, Zahra; Gesztelyi, Rudolf; Varga, Balazs; Haines, David; Bombicz, Mariann; Tosaki, Arpad; Juhasz, Bela

    2013-01-01

    Mutagenicity and liver toxicity of the herb tarragon (Artemisia dracunculus) were evaluated using single cell gel (comet) electrophoresis. Ten microlitres aliquots of peripheral venous human blood were incubated with tarragon extract, saline, or the mutagen sodium dichromate. Cell suspensions dispersed in low-melting agarose were electrophoresed in ethidium bromide. The resulting DNA migration trails were obtained using fluorescent microscopy at 400× magnification, and graded according to the mutagenicity index (MI) for each cell incubation condition. The in vivo liver toxicity of Artemisia dracunculus was assessed in the blood of mice treated orally with the extract of the herb, using alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as liver function indicators. Liver morphology was assessed using hematoxylin and eosin (HE) staining of liver tissue. The present study demonstrated a direct correlation between tarragon extract dosage and three major outcome variables: MI; serum liver enzyme activity; and liver histopathology. These outcomes are possibly due to the presence in tarragon of methylchavicol and other genotoxic compounds. These findings provide a preliminary guide for risk assessment of tarragon in diet and in possible therapeutic applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. PUBLIC SOURCES OF MUTAGENICITY AND CARCINOGENICITY DATA: USE IN STRUCTURE-ACTIVITY RELATIONSHIP MODELS

    EPA Science Inventory

    No Abstract - first paragraph of INTRODUCTION

    Publicly supported compilations of mutagenicity and carcinogenicity data are available
    for a significant number and variety of environmental and industrial chemicals and, to a lesser
    extent, pharmaceutical chemicals. T...

  15. Cytotoxic, mutagenicity, and genotoxicity effects of guanylhydrazone derivatives.

    PubMed

    Pinhatti, Valéria Rodrigues; da Silva, Juliana; Martins, Tales Leandro Costa; Moura, Dinara Jaqueline; Rosa, Renato Moreira; Villela, Izabel; Stopiglia, Cheila Denise Ottonelli; da Silva Santos, Selma; Scroferneker, Maria Lúcia; Machado, Carlos Renato; Saffi, Jenifer; Henriques, João Antonio Pêgas

    2016-08-01

    Several studies have reported that guanylhydrazones display a variety of desirable biological properties, such as antihypertensive, antibacterial, and antimalarial behaviour. They furthermore promote anti-pneumocystosis and anti-trypanosomiasis, exhibit antitumor activity, and show significant cytotoxicity against cancer cell lines. In this work, we have evaluated the cytotoxicity, mutagenicity, and genotoxicity of two guanylhydrazones derivatives, (E)-2-[(2,3-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (2,3-DMeB) and (E)-2-[(3,4-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (3,4-DMeB), in different biological models. Both 2,3-DMeB and 3,4-DMeB induce weak cytotoxic and mutagenic effects in bacteria and yeast. The genotoxicity of these compounds was determined in a fibroblast cell line (V79) using alkaline comet assay, as well as a modified comet assay with bacterial enzymes formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (EndoIII). Both guanylhydrazone derivatives induced DNA damage. Treatment of V79 cells with EndoIII and FPG proteins demonstrated a significant effect of 2,3-DMeB and 3,4-DMeB with respect to oxidized bases. In addition, the derivatives induced a significant increase in the frequency of micronucleated cells at high doses. The antifungal and anti-trypanosomal properties of these guanylhydrazone derivatives were also evaluated, and the obtained results suggest that 2,3-DMeB is more effective than 3,4-DMeB. The biological activity of 2,3-DMeB and 3,4-DMeB may thus be related, at least in part, to their oxidative potential, as well as to their ability to interact with DNA. Considering the previously reported in vitro antitumor activity of guanylhydrazone derivatives in combination with the lack of acute toxicity and the fact that DNA damage is only observed at high doses should render both compounds good candidates for in vivo studies on antitumor activity. Copyright © 2016 Elsevier B

  16. Mutagens from the cooking of food. III. Survey by Ames/Salmonella test of mutagen formation in secondary sources of cooked dietary protein.

    PubMed

    Bjeldanes, L F; Morris, M M; Felton, J S; Healy, S; Stuermer, D; Berry, P; Timourian, H; Hatch, F T

    1982-08-01

    A survey of mutagen formation during the cooking of a variety of protein-rich foods that are minor sources of protein intake in the American diet is reported (see Bjeldanes, Morris, Felton et al. (1982) for survey of major protein foods). Milk, cheese, tofu and organ meats showed negligible mutagen formation except following high-temperature cooking for long periods of time. Even under the most extreme conditions, tofu, cheese and milk exhibited fewer than 500 Ames/Salmonella typhimurium revertants/100 g equivalents (wet weight of uncooked food), and organ meats only double that amount. Beans showed low mutagen formation after boiling and boiling followed by frying (with and without oil). Only boiling of beans followed by baking for 1 hr gave appreciable mutagenicity (3650 revertants/100g equivalents). Seafood samples gave a variety of results: red snapper, salmon, trout, halibut and rock cod all gave more than 1000 revertants/100 g wet weight equivalents when pan-fried or griddle-fried for about 6 min/side. Baked or poached rock and deep-fried shrimp showed no significant mutagen formation. Broiled lamb chops showed mutagen formation similar to that in red meats tested in the preceding paper: 16,000 revertants/100 g equivalents. These findings show that as measured by bioassay in S. typhimurium, most of the foods that are minor sources of protein in the American diet are also minor sources of cooking-induced mutagens.

  17. Safety Evaluation of Turmeric Polysaccharide Extract: Assessment of Mutagenicity and Acute Oral Toxicity

    PubMed Central

    Velusami, Chandrasekaran Chinampudur; Boddapati, Srinivasa Rao; Hongasandra Srinivasa, Srikanth; Richard, Edwin Jothie; Balasubramanian, Murali

    2013-01-01

    Curcuma longa Linn. (Zingiberaceae) commonly known as turmeric has long been used for centuries as a spice and household remedy. The present study was carried out to assess the possible mutagenic potential and acute oral toxicity of polysaccharide extract of turmeric rhizome (NR-INF-02) using standard tests. The standard battery of in vitro genotoxicity tests, bacterial reverse mutation test (BRMT), chromosome aberration (CA), and micronucleus (MN) tests were employed to assess the possible mutagenic activity of NR-INF-02 (Turmacin). The results showed no mutagenic effect with NR-INF-02 up to a dose of 5000 µg/mL in BRMT. The results on CA and MN tests revealed the non clastogenic activity of NR-INF-02 in a dose range of 250.36 to 2500 µg/mL with and without metabolic activation (S9). In acute oral toxicity study, NR-INF-02 was found to be safe up to 5 g/kg body weight in Wistar rats. Overall, results indicated that polysaccharide extract of C. longa was found to be genotoxically safe and also exhibited maximum tolerable dose of more than 5 g/kg rat body weight. PMID:24455673

  18. Mutagenicity and genotoxicity of drinking water in Guelma region, Algeria.

    PubMed

    Abda, Ahlem; Benouareth, Djamel E; Tabet, Mouna; Liman, Recep; Konuk, Muhsin; Khallef, Messaouda; Taher, Ali

    2015-02-01

    In this study, a battery of genotoxicity assays for monitoring drinking water was performed to assess the quality of the water resulting from the treatment plants. Five different types of samples were collected: raw water (P1), treated after pre-chlorination (P2), treated after decantation (P3), treated post-chlorination (P4), and consumers' taps (P5-P12). This study aims to evaluate the formation/occurrence of mutagenic and/or genotoxic compounds in surface drinking waters treated with chlorine disinfectant, during four seasonal experiments: summer, autumn, winter, and spring between 2012 and 2013 by bacterial reverse mutation assay in both Salmonella typhimurium TA98 and TA100 strains with or without metabolic activation system (S9 mix) and Allium cepa root meristematic cells, respectively. All of water samples, except at P1, P2, and P5 in summer; P1 in autumn; and P1 and P3-P12 in spring without S9 mix, and at P1 and P2 in summer and P6 and P8-P12 in spring with S9 mix, were found to be mutagenic in S. typhimurium TA98. However, only P11 and P12 in winter were found to be mutagenic for TA100 without S9 mix. The tested preparations in Allium anaphase-telophase test revealed a significant decrease in mitotic index (MI) and a simultaneous increase in chromosome aberrations (CAs) compared to the control. The bridge, stickiness, vagrant chromosomes, and disturbed chromosome aberrations were observed in anaphase-telophase cells. Physicochemical analysis, trihalomethanes (THMs), romoform (CHBr3), chloroform (CHCl3), bromodichloromethane (CHBrCl2), and dibromochloromethane (CHBr2Cl) levels in water samples were also determined. The results show also that this short-term battery tests are applicable in the routine monitoring of drinking water quality before and after distribution.

  19. THE CONTRIBUTION OF AZO DYES TO THE MUTAGENIC ACTIVITY OF THE CRISTAIS RIVER

    EPA Science Inventory

    To verify if compounds within the discharge of a dye processing plant were contributing to the mutagenicity repeatedly found in the Cristais River, Sao Paulo, Brazil, we chemically characterized the treated industrial effluent, raw and treated water, and the sludge produced by a ...

  20. Structure-mutagenicity relationship of kaurenoic acid from Xylopia sericeae (Annonaceae).

    PubMed

    Cavalcanti, B C; Ferreira, J R O; Moura, D J; Rosa, R M; Furtado, G V; Burbano, R R; Silveira, E R; Lima, M A S; Camara, C A G; Saffi, J; Henriques, J A P; Rao, V S N; Costa-Lotufo, L V; Moraes, M O; Pessoa, C

    2010-08-30

    Kaurane diterpenes are considered important compounds in the development of new highly effective anticancer chemotherapeutic agents. Genotoxic effects of anticancer drugs in non-tumour cells are of special significance due to the possibility that they induce secondary tumours in cancer patients. In this context, we evaluated the genotoxic and mutagenic potential of the natural diterpenoid kaurenoic acid (KA), i.e. (-)-kaur-16-en-19-oic acid, isolated from Xylopia sericeae St. Hill, using several standard in vitro and in vivo protocols (comet, chromosomal aberration, micronucleus and Saccharomyces cerevisiae assays). Also, an analysis of structure-activity relationships was performed with two natural diterpenoid compounds, 14-hydroxy-kaurane (1) and xylopic acid (2), isolated from X. sericeae, and three semi-synthetic derivatives of KA (3-5). In addition, considering the importance of the exocyclic double bond (C16) moiety as an active pharmacophore of KA cytotoxicity, we also evaluated the hydrogenated derivative of KA, (-)-kauran-19-oic acid (KAH), to determine the role of the exocyclic bond (C16) in the genotoxic activity of KA. In summary, the present study shows that KA is genotoxic and mutagenic in human peripheral blood leukocytes (PBLs), yeast (S. cerevisiae) and mice (bone marrow, liver and kidney) probably due to the generation of DNA double-strand breaks (DSB) and/or inhibition of topoisomerase I. Unlike KA, compounds 1-5 and KAH are completely devoid of genotoxic and mutagenic effects under the experimental conditions used in this study, suggesting that the exocyclic double bond (C16) moiety may be the active pharmacophore of the genetic toxicity of KA. 2010 Elsevier B.V. All rights reserved.

  1. Microbial mutagenic effects of the DNA minor groove binder pibenzimol (Hoechst 33258) and a series of mustard analogues.

    PubMed

    Ferguson, L R; Denny, W A

    1995-06-01

    A series of aniline mustards and half-mustards targeted to DNA by linkage (through a polymethylene chain) to the bisbenzimidazole chromophore of pibenzimol (Hoechst 33258) have been evaluated for their mutagenic properties, as estimated in three strains of Salmonella typhimurium, and for their mitotic crossing-over and petite mutagenesis activities in Saccharomyces cerevisiae strain D5. Agarose gel electrophoresis studies showed that only the derivative with the longest linker chain cross-linked DNA, with the remaining compounds being monoalkylators. The parent (non-alkylator) minor groove binding ligand (Hoechst 33258) was inactive in the bacterial strains TA98 or TA100 but weakly mutagenic in TA102, and caused neither mitotic crossing-over nor 'petite' mutagenesis in yeast. Aniline half-mustard itself (monoalkylator) was an effective base-pair substitution mutagen (events in S. typhimurium strain TA100) with some frameshift mutagenesis activity in TA98, but showed only weak effects in the yeast assays, whereas aniline mustard (cross-linker) was inactive in these bacterial systems but caused substantial amounts of mitotic crossing-over in yeast. The composite molecules studied here showed effects more characteristic of the minor groove binding chromophore than of alkylating moieties. All showed weak mutagenic activity in TA102 and none in TA98. The only compound to show significant mitotic crossing-over ability was the long-chain derivative which cross-linked DNA. For most of the compounds, the mutagenicity data provided no supportive evidence for DNA alkylation. Since other evidence suggests this does occur readily, it is likely to have a different target to that seen with untargeted aniline mustards. The significant antitumor activity and low mutagenic potential shown by these compounds make them worthy of further study.

  2. Evaluation of toxic, cytotoxic, mutagenic, and antimutagenic activities of natural and technical cashew nut shell liquids using the Allium cepa and Artemia salina bioassays.

    PubMed

    Leite, Aracelli de Sousa; Dantas, Alisson Ferreira; Oliveira, George Laylson da Silva; Gomes Júnior, Antonio L; de Lima, Sidney Gonçalo; Citó, Antônia Maria das Graças Lopes; de Freitas, Rivelilson M; Melo-Cavalcante, Ana Amélia de C; Dantas Lopes, José Arimateia

    2015-01-01

    The cashew nut releases a substance that is known as cashew nut shell liquid (CNSL). There are both natural (iCNSL) and technical (tCNSL) cashew nut shell liquids. This study used an Artemia salina bioassay to evaluate the toxic effects of iCNSL and tCNSL cashew nut shell liquids. It also evaluated the toxicity, cytotoxicity, and mutagenicity of CNSL and its effects on the damage induced by copper sulfate (CuSO4·5H2O) on the meristems' root of Allium cepa. Effects of the damage induced by CuSO4·5H2O were evaluated before (pre-), during (co-), and after (post-) treatments. The iCNSL contained 94.5% anacardic acid, and the tCNSL contained 91.3% cardanol. The liquids were toxic to A. salina. Toxicity, cytotoxicity, and mutagenicity were observed with iCNSL compared with the negative control. Similarly, iCNSL failed to inhibit the toxicity and cytotoxicity of CuSO4·5H2O. The tCNSL was not toxic, cytotoxic, or mutagenic in any of the concentrations. However, the lowest iCNSL concentrations and all of the tCNSL concentrations had preventive, antimutagenic, and reparative effects on micronuclei and on chromosomal aberrations in the A. cepa. Therefore, protective, modulating, and reparative effects may be observed in the A. cepa, depending on the concentration and type of CNSL used.

  3. ACTION OF MUTAGENIC AGENTS ON AUXOTROPHIC STRAINS OF STREPTOMYCES

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jarai, M.

    1962-01-01

    The mutagenic effect on Streptomyces auxotrophs of uv and x irradiation and of some chemical agerts was studied. From the observed reverse mutations it was concluded that uv and probably x irradiation have an optimal mutagenic dose. With nine auxotrophic strains it was shown that under the same conditions different gene loci reacted differently to the same mutagenic agent. With uy radiation, mutations occurred most frequently at doses falling within the range of 3500 to 4000 erg/mm/sup 2/. With such doses, the average mutation frequency for singly deficient mutants was 0.8 x 10/sup -6/, for doubly deficient mutants 8.4 xmore » 10/sup -8/. An analysis of the number of mutations as compared to the number of survivors in two biochemical mutants (N-4 and N-11) showed that with N- 4 the highest number of mutations was obtained at doses of 3500 to 4500 erg/mm/ sup 2/, namely, 12 to 15 per 10 surviving conidia, and with strain N-11, the highest frequency was obtained in the same dose range, namely, three to four mutations per 10/sup 6/ surviving conidia. The optimal dose of irradiation corresponds to 90 to 97% lethality. It was shown that, unlike the results with uv irradiation, with x rays no such definite relation existed between optimal dose and frequency of mutations. The highest mutation frequency occurred at doses of 20,000 to 25,000 r, which corresponded to 85 to 91% lethality. Of the chemical substances examined, a definite mutagenic action was exerted by acridine orange, streptomycin, hydroxylamine, phenyl, isocyannte, and 8-quinolinol. The maximum mutagenic frequency for survivors was 41.4 x 10/sup -6/ after uv irradiation (biochemical mutant arg 3-; frequency of sportaneous back mutation, 0.041 x 10/sup -6/). With x irradiation the maximum mutagenic frequency was 3.42 x 10/sup -6/ (biochemical mutant meth 1-; frequency of spontaneous back mutation, 0.28 X 10/sup -6/). With chemical agents the maximum mutation frequencies for the initial conidia number were as

  4. Circular dichroism study of the interaction between mutagens and bilirubin bound to different binding sites of serum albumins

    NASA Astrophysics Data System (ADS)

    Orlov, Sergey; Goncharova, Iryna; Urbanová, Marie

    Although recent investigations have shown that bilirubin not only has a negative role in the organism but also exhibits significant antimutagenic properties, the mechanisms of interactions between bilirubin and mutagens are not clear. In this study, interaction between bilirubin bound to different binding sites of mammalian serum albumins with structural analogues of the mutagens 2-aminofluorene, 2,7-diaminofluorene and mutagen 2,4,7-trinitrofluorenone were investigated by circular dichroism and absorption spectroscopy. Homological human and bovine serum albumins were used as chiral matrices, which preferentially bind different conformers of bilirubin in the primary binding sites and make it observable by circular dichroism. These molecular systems approximated a real system for the study of mutagens in blood serum. Differences between the interaction of bilirubin bound to primary and to secondary binding sites of serum albumins with mutagens were shown. For bilirubin bound to secondary binding sites with low affinity, partial displacement and the formation of self-associates were observed in all studied mutagens. The associates of bilirubin bound to primary binding sites of serum albumins are formed with 2-aminofluorene and 2,4,7-trinitrofluorenone. It was proposed that 2,7-diaminofluorene does not interact with bilirubin bound to primary sites of human and bovine serum albumins due to the spatial hindrance of the albumins binding domains. The spatial arrangement of the bilirubin bound to serum albumin along with the studied mutagens was modelled using ligand docking, which revealed a possibility of an arrangement of the both bilirubin and 2-aminofluorene and 2,4,7-trinitrofluorenone in the primary binding site of human serum albumin.

  5. Mutagenicity in drug development: interpretation and significance of test results.

    PubMed

    Clive, D

    1985-03-01

    The use of mutagenicity data has been proposed and widely accepted as a relatively fast and inexpensive means of predicting long-term risk to man (i.e., cancer in somatic cells, heritable mutations in germ cells). This view is based on the universal nature of the genetic material, the somatic mutation model of carcinogenesis, and a number of studies showing correlations between mutagenicity and carcinogenicity. An uncritical acceptance of this approach by some regulatory and industrial concerns is over-conservative, naive, and scientifically unjustifiable on a number of grounds: Human cancers are largely life-style related (e.g., cigarettes, diet, tanning). Mutagens (both natural and man-made) are far more prevalent in the environment than was originally assumed (e.g., the natural bases and nucleosides, protein pyrolysates, fluorescent lights, typewriter ribbon, red wine, diesel fuel exhausts, viruses, our own leukocytes). "False-positive" (relative to carcinogenicity) and "false-negative" mutagenicity results occur, often with rational explanations (e.g., high threshold, inappropriate metabolism, inadequate genetic endpoint), and thereby confound any straightforward interpretation of mutagenicity test results. Test battery composition affects both the proper identification of mutagens and, in many instances, the ability to make preliminary risk assessments. In vitro mutagenicity assays ignore whole animal protective mechanisms, may provide unphysiological metabolism, and may be either too sensitive (e.g., testing at orders-of-magnitude higher doses than can be ingested) or not sensitive enough (e.g., short-term treatments inadequately model chronic exposure in bioassay). Bacterial systems, particularly the Ames assay, cannot in principle detect chromosomal events which are involved in both carcinogenesis and germ line mutations in man. Some compounds induce only chromosomal events and little or no detectable single-gene events (e.g., acyclovir, caffeine

  6. Mutagenicity of pan residues and gravy from fried meat.

    PubMed

    Overvik, E; Nilsson, L; Fredholm, L; Levin, O; Nord, C E; Gustafsson, J A

    1987-02-01

    Lean pork meat was fried with or without the addition of frying-fat at 200 or 250 degrees C. The pan residues were collected by washing the hot pan with boiling water. When producing thickened gravy the water was substituted by a mixture of water and flour, milk and flour or cream and flour. The basic extracts were tested for mutagenicity in Ames' Salmonella test on strain TA98 with the addition of S9 mix. High amounts of mutagenicity were found in all samples. The amounts of mutagenicity in the pan residues were at a comparable level of the amounts found in the meat crusts. Thickening of the gravy caused only small changes in the mutagenicity.

  7. Flavonoid detection in hydroethanolic extract of Pouteria torta (Sapotaceae) leaves by HPLC-DAD and the determination of its mutagenic activity.

    PubMed

    Costa, Daryne L M G; Rinaldo, Daniel; Varanda, Eliana A; de Sousa, Juliana F; Nasser, Ana L M; Silva, Ana C Z; Baldoqui, Débora C; Vilegas, Wagner; dos Santos, Lourdes Campaner

    2014-10-01

    It is well known that phytotherapy has grown in popularity in recent years. Because a drug cannot be administered without ensuring its effectiveness and safety, the standardization and regulation of phytotherapeutic drugs are required by the global market and governmental authorities. This article describes a simple and reliable high-performance liquid chromatography-diode array detection analysis method for the simultaneous detection of myricetin-3-O-β-D-galactopyranoside, myricetin-3-O-α-L-arabinopyranoside, and myricetin-3-O-α-L-rhaminopyranoside present in the hydroethanolic extract (ethanol/H2O, 7:3, v/v) of Pouteria torta. The mutagenic activity of the extract was evaluated on Salmonella typhimurium and by an in vivo micronucleus test on the peripheral blood cells of Swiss mice. The linearity, sensitivity, selectivity, repeatability, accuracy, and precision of the assay were evaluated. The analytical curves were linear and exhibited good repeatability (with a deviation of less than 5%) and demonstrated good recovery (within the 83-107% range). The results demonstrate that the hydroethanolic extract exhibited a mutagenic activity in both assays, suggesting caution in the use of this plant in folk medicine.

  8. Flavonoid Detection in Hydroethanolic Extract of Pouteria torta (Sapotaceae) Leaves by HPLC-DAD and the Determination of Its Mutagenic Activity

    PubMed Central

    Costa, Daryne L.M.G.; Rinaldo, Daniel; Varanda, Eliana A.; de Sousa, Juliana F.; Nasser, Ana L.M.; Silva, Ana C.Z.; Baldoqui, Débora C.; Vilegas, Wagner

    2014-01-01

    Abstract It is well known that phytotherapy has grown in popularity in recent years. Because a drug cannot be administered without ensuring its effectiveness and safety, the standardization and regulation of phytotherapeutic drugs are required by the global market and governmental authorities. This article describes a simple and reliable high-performance liquid chromatography–diode array detection analysis method for the simultaneous detection of myricetin-3-O-β-D-galactopyranoside, myricetin-3-O-α-L-arabinopyranoside, and myricetin-3-O-α-L-rhaminopyranoside present in the hydroethanolic extract (ethanol/H2O, 7:3, v/v) of Pouteria torta. The mutagenic activity of the extract was evaluated on Salmonella typhimurium and by an in vivo micronucleus test on the peripheral blood cells of Swiss mice. The linearity, sensitivity, selectivity, repeatability, accuracy, and precision of the assay were evaluated. The analytical curves were linear and exhibited good repeatability (with a deviation of less than 5%) and demonstrated good recovery (within the 83–107% range). The results demonstrate that the hydroethanolic extract exhibited a mutagenic activity in both assays, suggesting caution in the use of this plant in folk medicine. PMID:25055245

  9. Biochemical mutagens affect the preservation of fungi and biodiversity estimations.

    PubMed

    Paterson, R Russell M; Lima, Nelson

    2013-01-01

    Many fungi have significant industrial applications or biosafety concerns and maintaining the original characteristics is essential. The preserved fungi have to represent the situation in nature for posterity, biodiversity estimations, and taxonomic research. However, spontaneous fungal mutations and secondary metabolites affecting producing fungi are well known. There is increasing interest in the preservation of microbes in Biological Resource Centers (BRC) to ensure that the organisms remain viable and stable genetically. It would be anathema if they contacted mutagens routinely. However, for the purpose of this discussion, there are three potential sources of biochemical mutagens when obtaining individual fungi from the environment: (a) mixtures of microorganisms are plated routinely onto growth media containing mutagenic antibiotics to control overgrowth by contaminants, (b) the microbial mixtures may contain microorganisms capable of producing mutagenic secondary metabolites, and (c) target fungi for isolation may produce "self" mutagens in pure culture. The probability that these compounds could interact with fungi undermines confidence in the preservation process and the potential effects of these biochemical mutagens are considered for the first time on strains held in BRC in this review.

  10. Environmental tobacco smoking, mutagen sensitivity, and head and neck squamous cell carcinoma.

    PubMed

    Zhang, Z F; Morgenstern, H; Spitz, M R; Tashkin, D P; Yu, G P; Hsu, T C; Schantz, S P

    2000-10-01

    Although active tobacco smoking has been considered a major risk factor for head and neck cancer, few studies have evaluated environmental tobacco smoke (ETS) and its interaction with mutagen sensitivity on the risk of head and neck cancer. We investigated the relationship between ETS and head and neck cancer in a case-control study of 173 previously untreated cases with pathologically confirmed diagnoses of squamous cell carcinoma of the head and neck and 176 cancer-free controls at Memorial Sloan-Kettering Cancer Center between 1992 and 1994. A structured questionnaire was used to collect ETS exposure and other covariates including a history of active tobacco smoking and alcohol use. ETS measures include a history of ETS exposure at home and at workplace. The associations between passive smoking and head and neck cancer were analyzed by Mantel-Haenszel methods and logistic regression models. Additive and multiplicative models were used to evaluate effect modifications between ETS and mutagen sensitivity. The crude odds ratio (OR) for ETS exposure was 2.8 [95% confidence intervals (CI), 1.3-6.0]. Controlling for age, sex, race, education, alcohol consumption, pack-years of cigarette smoking, and marijuana use, the risk of squamous cell carcinoma of the head and neck was increased with ETS (adjusted OR, 2.4; 95% CI, 0.9-6.8). Dose-response relationships were observed for the degree of ETS exposure; the adjusted ORs were 2.1 (95% CI, 0.7-6.1) for those with moderate exposure and 3.6 (95% CI, 1.1-11.5) for individuals with heavy exposure (P for trend = 0.025), in comparison with those who never had ETS exposures. These associations and the dose-response relationships were still present when the analysis was restricted to nonactive smoking cases and controls (crude OR, 2.2; 95% CI, 0.6-8.4). Crude odds ratios were 1.8 for those with moderate ETS exposure and 4.3 for individuals with heavy ETS exposure among nonsmoking cases and controls (P for trend = 0.008). More

  11. Antimutagenic effects of betel leaf extract against the mutagenicity of two tobacco-specific N-nitrosamines.

    PubMed

    Padma, P R; Amonkar, A J; Bhide, S V

    1989-03-01

    Epidemiological studies have implicated chewing tobacco alone to be more hazardous than chewing tobacco with betel quid. Experimental studies have shown that betel leaf is antimutagenic against standard mutagens like benzo[a]pyrene and dimethylbenz[a]anthracene. Since the tobacco-specific N-nitrosamines (TSNA) are the only carcinogens present in unburnt forms of tobacco, including chewing tobacco, we tested the effect of an extract of betel leaf against the mutagenicity of the two important TSNA, viz., N'-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, using the Ames Salmonella/microsome assay with TA100 +S9 and the in vivo micronucleus test. In both the test systems it was observed that betel leaf extract suppressed the mutagenic effects of both the nitrosamines to a significant extent.

  12. Evaluation of photo-mutagenicity and photo-cytotoxicity of food coloring agents.

    PubMed

    Arimoto-Kobayashi, Sakae; Machida, Masaki; Okamoto, Keinosuke; Yamaguchi, Akie

    2005-05-01

    Pigments extracted from natural products are widely used for food coloration in Japan. An investigation concerning the photo-mutagenicity and photo-carcinogenicity of frequently used colorants in Japan was performed. Colorants examined were from Laccifer lacca (lac-color), Coccus cacti (cochineal-color), Carthamus tinctorius (carthamus yellow), Gardenia augusta (gardenia yellow and gardenia blue), Monascus anka and Monascus purpureus (monascus red), the skin of Vitis vinifera and Vitis labrusca (grape-skin color), Tamarindus indica (tamarind brown) and Beta vulgaris (beet red). No significant increase in bacterial mutation was found when Salmonella typhimurium TA98, TA100 and TA102 were simultaneously treated with colorants and subjected to UVA irradiation for 30 min. When colorant solutions were subjected to UVA irradiation for 4 h, irradiated solutions containing lac-color became slightly mutagenic toward S.typhimurium TA98 without metabolic activation. A decrease in cell survival resulted when WTK-1 cells were subjected to UVA irradiation for 60 min in the presence of purpurin at 1 mg/ml. Delayed cytotoxicity was also observed following 24 h incubation in fresh medium of samples that were subjected to UVA irradiation for 60 min in the presence of colorant (carthamus yellow, grape-skin color, gardenia blue, cochineal-color, monascus red or purpurin).

  13. Mutagenicity and Acute Oral Toxicity Test for Herbal Poultry Feed Supplements.

    PubMed

    Srinivasa Rao, Boddapati; Chandrasekaran, C V; Srikanth, H S; Sasikumar, Murugan; Edwin Jothie, R; Haseena, Begum; Bharathi, Bethapudi; Selvam, Ramasamy; Prashanth, D'Souza

    2018-01-01

    Herbal products are being used and trusted globally for thousands of years for their health benefits and limited side effects. Globally, a general belief amongst the consumers is that herbal supplements are always safe because they are "natural." But later, research reveals that they may not be safe. This raises concern on their safety and implications for their use as feed supplement or medicine. Toxicity testing can reveal some of the risks that may be associated with use of herbs, therefore avoiding potential harmful effects. The present study was designed to investigate five poultry feed supplements (PFS), EGMAX® (to revitalize ovarian activity), FEED-X ™ (feed efficiency enhancer), KOLIN PLUS ™ (natural replacer of synthetic choline chloride), PHYTOCEE® (natural defence enhancer), and STODI® (to prevent and control loose droppings), for their possible mutagenicity and toxicity. Bacterial reverse mutation (BRMT) and acute oral toxicity tests were employed to assess the PFS for their possible mutagenicity and toxicity. Results indicated that the PFS were devoid of mutagenic effects in BRMT and showed higher safety profile in rodent acute oral toxicity test.

  14. [Hygienic evaluation of the total mutagenic activity of snow samples from Magnitogorsk].

    PubMed

    Legostaeva, T B; Ingel', F I; Antipanova, N A; Iurchenko, V V; Iuretseva, N A; Kotliar, N N

    2010-01-01

    The paper gives the results of 4-year monitoring of the total mutagenic activity of snow samples from different Magnitogork areas in a test for induction of dominant lethal mutations (DLM) in the gametes of Drosophila melanogaster. An association was first found between the rate of DLM and the content of some chemical compounds in the ambient air and snow samples; moreover all the substances present in the samples, which had found genotoxic effects, showed a positive correlation with the rate of DLM. Furthermore, direct correlations were first established between the rate of DLM and the air pollution index and morbidity rates in 5-7-year-old children residing in the areas under study. The findings allow the test for induction of dominant lethal mutations (DLM) in the gametes of Drosophila melanogaster to be recommended due to its unique informative and prognostic value for monitoring ambient air pollution and for extensive use in the risk assessment system.

  15. In vivo evaluation of mutagenic and recombinagenic activities of Brazilian propolis.

    PubMed

    Rodrigues, Carmem Regine Faleiro; Plentz, Luciana Ciarelli; Marcucci, Maria Cristina; Dihl, Rafael Rodrigues; Lehmann, Mauricio

    2016-10-01

    Propolis is a resinous, complex mixture of compounds collected by the bee species Apis mellifera. This study investigated the genotoxicity of green and brown propolis collected in southeast Brazil using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. The effect of five concentrations (0.5, 1.0, 2.0, 4.0, and 7.5 mg/mL) of both propolis types was analyzed in standard (ST) and high-bioactivation (HB) crosses, which have normal and high levels of cytochrome P450 enzymes, respectively. The results show that the types of propolis evaluated have no mutagenic action, in either cross. Moreover, chromatography findings revealed that the propolis types analyzed have different chemical compositions. Brown propolis had lower levels of polyphenols (∼7.2 mg/mL), compared to the green type (34.9 mg/g). Taken together, the findings of the present study and literature reports point to the safety in consuming low amounts of propolis, considering the risk of genetic damage, and confirm the absence of mutagenic and recombinagenic actions of the propolis types investigated. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Radiation and chemical mutagen induced somaclonal variations through in vitro organogenesis of cotton (Gossypium hirsutum L.).

    PubMed

    Muthusamy, Annamalai; Jayabalan, Narayanasamy

    2014-12-01

    The purpose of the investigation was to induce somaclonal variations by gamma rays (GR), ethylmethane sulphonate (EMS) and sodium azide (SA) during in vitro organogenesis of cotton. The shoot tip explants were irradiated with 5-50 Gray (Gy) GR (Cobalt 60), 0.5-5.0 mM EMS and SA separately, and inoculated on Murashige and Skoog (MS) medium fortified with plant growth regulator (PGR) for organogenesis. The plantlets with well-developed root systems were acclimatized and transferred into the experimental field to screen the somaclonal variations during growth and development. The number of somaclonal variations was observed in growth of irradiated/treated shoot tips, multiplication, plantlet regeneration and growth in vitro and ex vitro. The lower doses/concentrations of mutagenic treatments showed significant enhancement in selected agronomical characters and they showed decreased trends with increasing doses/concentrations of mutagenic agents. The results of the present study revealed the influence of lower doses/concentrations of mutagenic treatments on in vitro and ex vitro growth of cotton plantlets and their significant improvement in agronomical characters which needs further imperative stability analysis. The present observations showed the platform to use lower doses/concentrations of mutagenic agents to induce variability for enhanced agronomical characters, resistant and tolerant cotton varieties.

  17. Nitroreductase-dependent mutagenicity of p-nitrophenylhydroxylamine and its N-acetyl and N-formyl hydroxamic acids.

    PubMed

    Corbett, M D; Wei, C; Corbett, B R

    1985-05-01

    p-Nitrophenylhydroxylamine (NPH) and two hydroxamic acids derived from it were synthesized and subjected to mutagenicity testing in Salmonella typhimurium strains TA98, TA98NR, TA1538 and TA1538NR. In addition, p-dinitrobenzene (DNB), p-nitroaniline (NA) and p-nitroacetanilide (AcNA) were simultaneously examined for mutagenic action against these four tester strains. NPH, its N-acetyl (AcNPH) and N-formyl (FoNPH) derivatives, and also DNB displayed strong mutagenic action to the nitroreductase-containing strains, TA98 and TA1538. NPH was the most potent chemical in this series against both of these strains, while the two hydroxamic acids AcNPH and FoNPH, and also DNB displayed approximately the same degree of mutagenicity. In the nitroreductase-deficient strains, TA98NR and TA1538NR, the mutagenicity of these four compounds was markedly reduced. The necessity for nitroreduction in order to activate these promutagens is fairly certain; however, the lack of mutagenicity of NA and AcNA towards all four tester strains made the interpretation of these data somewhat more complicated. Several possible bioactivation pathways were presented, with one mechanism in particular being proposed. This mechanism requires only that the strong electron-withdrawing nitro group be converted to an electron-donating group by bacterial nitroreductase. Such a mechanism is unique for the bioactivation of nitro aromatics by nitroreductase, since the enzymatic reduction need not produce the intermediary hydroxylamine metabolite.

  18. Evaluation of Toxic, Cytotoxic, Mutagenic, and Antimutagenic Activities of Natural and Technical Cashew Nut Shell Liquids Using the Allium cepa and Artemia salina Bioassays

    PubMed Central

    Leite, Aracelli de Sousa; Oliveira, George Laylson da Silva; Gomes Júnior, Antonio L.; de Lima, Sidney Gonçalo; Citó, Antônia Maria das Graças Lopes; de Freitas, Rivelilson M.; Melo-Cavalcante, Ana Amélia de C.; Dantas Lopes, José Arimateia

    2015-01-01

    The cashew nut releases a substance that is known as cashew nut shell liquid (CNSL). There are both natural (iCNSL) and technical (tCNSL) cashew nut shell liquids. This study used an Artemia salina bioassay to evaluate the toxic effects of iCNSL and tCNSL cashew nut shell liquids. It also evaluated the toxicity, cytotoxicity, and mutagenicity of CNSL and its effects on the damage induced by copper sulfate (CuSO4·5H2O) on the meristems' root of Allium cepa. Effects of the damage induced by CuSO4·5H2O were evaluated before (pre-), during (co-), and after (post-) treatments. The iCNSL contained 94.5% anacardic acid, and the tCNSL contained 91.3% cardanol. The liquids were toxic to A. salina. Toxicity, cytotoxicity, and mutagenicity were observed with iCNSL compared with the negative control. Similarly, iCNSL failed to inhibit the toxicity and cytotoxicity of CuSO4·5H2O. The tCNSL was not toxic, cytotoxic, or mutagenic in any of the concentrations. However, the lowest iCNSL concentrations and all of the tCNSL concentrations had preventive, antimutagenic, and reparative effects on micronuclei and on chromosomal aberrations in the A. cepa. Therefore, protective, modulating, and reparative effects may be observed in the A. cepa, depending on the concentration and type of CNSL used. PMID:25861638

  19. Mutagenic potential assessment associated with human exposure to natural radioactivity.

    PubMed

    Marcon, Alexandre Endres; Navoni, Julio Alejandro; de Oliveira Galvão, Marcos Felipe; Garcia, Anuska Conde Fagundes Soares; do Amaral, Viviane Souza; Petta, Reinaldo Antônio; Campos, Thomas Ferreira da Costa; Panosso, Renata; Quinelato, Antônio Luiz; de Medeiros, Sílvia Regina Batistuzzo

    2017-01-01

    Lucrécia city, known to harbor a high cancer rate, is located in a semiarid region characterized by the presence of mineral reservoirs, facing a high exposure to metal and natural radioactivity. The present study aimed to assess the environmental scenario at a semiarid region located in Northeastern Brazil. Metal concentration, alpha and beta radiation, and cyanobacteria content in tap water along with indoor radon and gamma emitters (U, K and Th) concentrations were measured. In addition, mutagenic and nuclear instability effects were assessed using buccal micronucleus cytome assay. The study included five samplings corresponding to a period between 2007 and 2009. Drinking water from Lucrécia city presented levels of Mn, Ni and Cr along with cyanobacteria in concentrations one to four times higher than regulatory guidelines considered. Furthermore, high levels of all the tested radionuclides were found. A high percentage of the houses included in this study presented indoor radon concentrations over 100 Bq m -3 . The mean annual effective dose from Lucrécia houses was six times higher than observed in a control region. The levels of exposure in most of the Lucrécia houses were classified as middle to high. A significant mutagenic effect, represented as an increase of micronuclei (MN) frequency and nuclear abnormalities as nuclear buds (NB), binucleated cells (BN), and pyknotic cells (PYC) were found. The results obtained highlight the role of high background radioactivity on the observed mutagenic effect and could help to explain the exacerbated cancer rate reported in this locality. Copyright © 2016. Published by Elsevier Ltd.

  20. Cooking with Fire: The Mutagenicity- and PAH-Emission ...

    EPA Pesticide Factsheets

    Emissions from solid fuels used for cooking cause ~4 million premature deaths per year. Advanced solid-fuel cookstoves are a potential solution, but they should be assessed by appropriate performance indicators, including biological effects. We evaluated two categories of solid-fuel cookstoves for 8 pollutant- and 4 mutagenicity-emission factors, correlated the mutagenicity-emission factors, and compared them to those of other combustion emissions. We burned red oak in a 3-stone fire (TSF), a natural-draft stove (NDS), and a forced-draft stove (FDS); we combusted propane as a liquified petroleum gas control fuel. We determined emission factors based on useful energy (megajoules delivered, MJd) for carbon monoxide, nitrogen oxides (NOx), black carbon, methane, total hydrocarbons, 32 polycyclic aromatic hydrocarbons, PM2.5, levoglucosan (a wood-smoke marker), and mutagenicity in Salmonella. Other than NOx the emission factors per MJd correlated highly among each other (r2 ≥ 0.92); NOx correlated 0.58-0.76 with the other emission factors. Excluding NOx, the NDS and FDS reduced the emission factors on average 68 and 92%, respectively, relative to the TSF. Nonetheless, the mutagenicity-emission factor based on fuel energy used (MJthermal) for the most efficient stove (FDS) was intermediate to that of a large diesel bus engine and a small diesel generator. Both mutagenicity- and pollutant-emission factors may be informative for characterizing cookstove

  1. Ethanol- or acetone-pretreatment of mice strongly enhances the bacterial mutagenicity of dimethylnitrosamine in assays mediated by liver subcellular fraction, but not in host-mediated assays.

    PubMed

    Glatt, H; de Balle, L; Oesch, F

    1981-01-01

    The activation of dimethylnitrosamine (DMN) to a bacterial mutagen in liver subcellular fraction and in intrasanguinous host-mediated assays was studied, in particular the effect of pretreatment of the animals with ethanol or acetone. Salmonella typhimurium TA 92 was much more sensitive to DMN mutagenicity than TA 100 and TA 1535 or Escherichia coli WP2uvrA and was used for the main part of the study. Noteworthy, in part already known, features of the in vitro activation are the relatively low pH optimum (pH 6-6.4), the non-linear dose-mutagenic response-relationship and the relatively high doses of DMN required for activation with control preparations. Pretreatment of mice with ethanol or acetone greatly reduced the minimal mutagenically effective concentration of DMN in the in vitro assay. Pretreatment with Aroclor 1254, an inducer frequently used in mutagenicity research, showed little effect when used alone, but reduced the potentiation by acetone. The results of the host-mediated assays substantially differed from those of the in vitro activation assays (a) in the relatively low dose of DMN required for mutagenicity to occur and (b) in the lack of potentiation by acetone-or ethanol-pretreatment. Acetone even led to a marginal decrease in mutagenicity. As a possible explantation for this apparent discrepancy were assume that with the in vitro system the activity of the dilute metabolizing system is limiting for the activation of DMN and induction therefore will increase the mutagenicity, whereas in vivo DMN is quantitatively metabolized in both induced and non-induced animals. The results show that caution has to be taken in the interpretation from in vitro results to the in vivo situation. In particular our in vivo experiments do not support the hypothesis that the induction by ethanol of an activating system with a low Km (which would strongly activate traces of DMN ingested with many foods) is one of the reasons for the increased risk of liver tumors in

  2. Kaempferol, a mutagenic flavonol from Helichrysum simillimum.

    PubMed

    Elgorashi, Ee; van Heerden, Fr; van Staden, J

    2008-11-01

    Helichrysum simillimum is native to South Africa. It is used for the treatment of coughs, colds, fever, infections, headache, and menstrual pain. Extracts of this species showed mutagenic effects in the Salmonella/microsome assay. The aim of this study was to isolate and determine the mutagenic constituents of H. simillimum. Bioassay-guided fractionation of 90% aqueous methanol extracts, using Salmonella typhimurium TA98, led to the isolation of the flavonol kaempferol.

  3. Mutagenic and antimutagenic effects of aqueous extract of rosemary (Rosmarinus officinalis L.) on meristematic cells of Allium cepa.

    PubMed

    Felicidade, I; Lima, J D; Pesarini, J R; Monreal, A C D; Mantovani, M S; Ribeiro, L R; Oliveira, R J

    2014-11-28

    Polyphenolic compounds present in rosemary were found to have antioxidant properties, anticarcinogenic activity, and to increase the detoxification of pro-carcinogens. The aim of the study was to determine the effect the aqueous extract of rosemary (AER) on mutagenicity induced by methylmethane sulfonate in meristematic cells of Allium cepa, as well as to describe its mode of action. Anti-mutagenicity experiments were carried out with 3 different concentrations of AER, which alone showed no mutagenic effects. In antimutagenicity experiments, AER showed chemopreventive activity in cultured meristematic cells of A. cepa against exposure to methylmethane sulfonate. Additionally, post-treatment and simultaneous treatment using pre-incubation protocols were the most effective. Evaluation of different protocols and the percent reduction in DNA indicated bioantimutagenic as well desmutagenic modes of action for AER. AER may be chemopreventive and antimutagenic.

  4. Determination of mutagenicity of the precipitate formed by sodium hypochlorite and chlorhexidine using the Ames test.

    PubMed

    Patil, Pranali; Aminoshariae, Anita; Harding, Jarrod; Montagnese, Thomas A; Mickel, Andre

    2016-04-01

    The aim of this study was to determine the direct mutagenic potential of any precipitate formed by combining sodium hypochlorite (NaOCl) and chlorhexidine (CHX). The precipitates formed by NaOCl and CHX were dissolved in 100% dimethyl sulfoxide and cultured with mutant Salmonella Typhimurium strains. The cells were observed for reverse mutation. The numbers of positive/mutated wells were statistically compared with those in the background plates using the two-sample proportion independent t-test. The precipitates were not found to be significantly more mutagenic than the background plates. Within the limitations of this study, the results suggest that the precipitates formed when sodium hypochlorite and chlorhexidine contact did not show mutagenic (and are therefore carcinogenic) potential. © 2015 Australian Society of Endodontology.

  5. Mutagenic, cytotoxic, and teratogenic effects of 2-acetylaminofluorene and reactive metabolites in vitro.

    PubMed

    Faustman-Watts, E M; Yang, H Y; Namkung, M J; Greenaway, J C; Fantel, A G; Juchau, M R

    1984-01-01

    The embryotoxic, mutagenic, and cytotoxic properties of 2-acetylaminofluorene (AAF) and two of its reactive metabolites, N-acetoxy-2-acetylaminofluorene (AAAF) and 2-nitrosofluorene (NF) were assessed in vitro. A combined embryo culture/biotransformation system was used to determine the ability of these compounds to produce embryonic malformations, growth retardation, and/or embryolethality. Salmonella typhimurium auxotrophs (his-) were utilized to measure the mutagenic and cytotoxic potentials of these compounds. The parent compound, AAF, did not produce embryonic malformations or mutagenicity in the absence of an added cytochrome P-450-dependent monooxygenase system. Both metabolites produced each of the measured toxic effects without supplementation of a bioactivation system. However, the three chemicals each elicited a different spectrum of malformations. Bioactivated AAF produced neural tube abnormalities, whereas embryos treated with AAAF primarily exhibited prosencephalic malformations, and NF produced abnormalities of axial rotation or flexure. NF was approximately ten times more potent than AAAF as a direct-acting mutagen but only slightly more active in producing embryonic malformations in vitro. The results indicated that differential effects on the various measured parameters could be produced by these chemicals. The results indicated further that neither NF nor AAAF appeared to be individually responsible for the neural tube abnormalities generated by biotransformed AAF.

  6. Influence of particulate trap oxidizers on emission of mutagenic compounds by diesel automobiles.

    PubMed

    Rasmussen, R E; Devillez, G; Smith, L R

    1989-06-01

    Diesel exhaust particles are known to contain mutagenic and carcinogenic chemicals. The aim of this study was to determine whether, and to what extent, catalytic particulate trap oxidizers on light-duty diesel engines may reduce the emission of particle-associated mutagenic chemicals into the environment. Exhaust particles were collected from Mercedes Benz and Volkswagen diesel automobiles, equipped with or without the manufacturer's exhaust traps, while running on a chassis dynamometer under specified load conditions. Exhaust particles were collected from a dilution tunnel onto 20" X 20" Teflon-coated fiberglass filters. Mutagenesis tests of dichloromethane (DCM) extracts of the particles were conducted using the Ames Salmonella bacterial test system. The mutation rate was calculated in terms of histidine revertants per mile of travel during a set of standard test cycles. With both vehicles the traps produced an 87-92% reduction in the total amount of particulate material collected by the filters. There was no significant change in the specific mutagenic activity (revertants per microgram of DCM particle extract) with or without the traps. These studies support the notion that installation of exhaust traps which reduce particulate emission on diesel-powered vehicles will also reduce the emission of particle-associated mutagenic and carcinogenic materials into the environment.

  7. Evaluation of the mutagenicity and carcinogenicity of motor vehicle emissions in short-term bioassays.

    PubMed Central

    Lewtas, J

    1983-01-01

    Incomplete combustion of fuel in motor vehicles results in the emission of submicron carbonaceous particles which, after cooling and dilution, contain varying quantities of extractable organic constituents. These organics are mutagenic in bacteria. Confirmatory bioassays in mammalian cells provide the capability of detecting chromosomal and DNA damage in addition to gene mutations. In order to evaluate the mutagenicity of these organics in mammalian cells, extractable organics from particle emissions from several diesel and gasoline vehicles were compared in a battery of microbial, mammalian cell and in vivo bioassays. The mammalian cell mutagenicity bioassays were selected to detect gene mutations, DNA damage, and chromosomal effects. Carcinogenesis bioassays conducted included short-term assays for oncogenic transformation and skin tumorigenesis. The results in different assay systems are compared both qualitatively and quantitatively. Good quantitative correlations were observed between several mutagenesis and carcinogenesis bioassays for this series of diesel and gasoline emissions. PMID:6186475

  8. Computational identification of structural factors affecting the mutagenic potential of aromatic amines: study design and experimental validation.

    PubMed

    Slavov, Svetoslav H; Stoyanova-Slavova, Iva; Mattes, William; Beger, Richard D; Brüschweiler, Beat J

    2018-07-01

    A grid-based, alignment-independent 3D-SDAR (three-dimensional spectral data-activity relationship) approach based on simulated 13 C and 15 N NMR chemical shifts augmented with through-space interatomic distances was used to model the mutagenicity of 554 primary and 419 secondary aromatic amines. A robust modeling strategy supported by extensive validation including randomized training/hold-out test set pairs, validation sets, "blind" external test sets as well as experimental validation was applied to avoid over-parameterization and build Organization for Economic Cooperation and Development (OECD 2004) compliant models. Based on an experimental validation set of 23 chemicals tested in a two-strain Salmonella typhimurium Ames assay, 3D-SDAR was able to achieve performance comparable to 5-strain (Ames) predictions by Lhasa Limited's Derek and Sarah Nexus for the same set. Furthermore, mapping of the most frequently occurring bins on the primary and secondary aromatic amine structures allowed the identification of molecular features that were associated either positively or negatively with mutagenicity. Prominent structural features found to enhance the mutagenic potential included: nitrobenzene moieties, conjugated π-systems, nitrothiophene groups, and aromatic hydroxylamine moieties. 3D-SDAR was also able to capture "true" negative contributions that are particularly difficult to detect through alternative methods. These include sulphonamide, acetamide, and other functional groups, which not only lack contributions to the overall mutagenic potential, but are known to actively lower it, if present in the chemical structures of what otherwise would be potential mutagens.

  9. MUTAGENICITY OF TEFLON-COATED GLASS FIBER FILTERS: A POTENTIAL PROBLEM AND SOLUTIONS

    EPA Science Inventory

    Teflon-coated glass fiber filters, used in studies of airborne particulate matter, were tested for mutagenic activity using the Salmonella/mammalian-microsome (Ames) assay. For each sample, eight blank filters were simultaneously extracted with dichloromethane (DCM), and the extr...

  10. dbAMEPNI: a database of alanine mutagenic effects for protein–nucleic acid interactions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Ling; Xiong, Yi; Gao, Hongyun

    Protein–nucleic acid interactions play essential roles in various biological activities such as gene regulation, transcription, DNA repair and DNA packaging. Understanding the effects of amino acid substitutions on protein–nucleic acid binding affinities can help elucidate the molecular mechanism of protein–nucleic acid recognition. Until now, no comprehensive and updated database of quantitative binding data on alanine mutagenic effects for protein–nucleic acid interactions is publicly accessible. Thus, we developed a new database of Alanine Mutagenic Effects for Protein-Nucleic Acid Interactions (dbAMEPNI). dbAMEPNI is a manually curated, literature-derived database, comprising over 577 alanine mutagenic data with experimentally determined binding affinities for protein–nucleic acidmore » complexes. Here, it contains several important parameters, such as dissociation constant (Kd), Gibbs free energy change (ΔΔG), experimental conditions and structural parameters of mutant residues. In addition, the database provides an extended dataset of 282 single alanine mutations with only qualitative data (or descriptive effects) of thermodynamic information.« less

  11. dbAMEPNI: a database of alanine mutagenic effects for protein–nucleic acid interactions

    DOE PAGES

    Liu, Ling; Xiong, Yi; Gao, Hongyun; ...

    2018-04-02

    Protein–nucleic acid interactions play essential roles in various biological activities such as gene regulation, transcription, DNA repair and DNA packaging. Understanding the effects of amino acid substitutions on protein–nucleic acid binding affinities can help elucidate the molecular mechanism of protein–nucleic acid recognition. Until now, no comprehensive and updated database of quantitative binding data on alanine mutagenic effects for protein–nucleic acid interactions is publicly accessible. Thus, we developed a new database of Alanine Mutagenic Effects for Protein-Nucleic Acid Interactions (dbAMEPNI). dbAMEPNI is a manually curated, literature-derived database, comprising over 577 alanine mutagenic data with experimentally determined binding affinities for protein–nucleic acidmore » complexes. Here, it contains several important parameters, such as dissociation constant (Kd), Gibbs free energy change (ΔΔG), experimental conditions and structural parameters of mutant residues. In addition, the database provides an extended dataset of 282 single alanine mutations with only qualitative data (or descriptive effects) of thermodynamic information.« less

  12. Mutagenicity testing in the Salmonella typhimurium assay of phenolic compounds and phenolic fractions obtained from smokehouse smoke condensates.

    PubMed

    Pool, B L; Lin, P Z

    1982-08-01

    Smokehouse smoke, which is used for flavouring meat products, was investigated for its mutagenic activity in the Salmonella typhimurium assay. We were chiefly concerned with the fractions free of polycyclic aromatic hydrocarbons but containing phenol compounds, which are responsible for the preservative and aromatizing properties of the smoke. The most abundantly occurring phenol compounds (phenol, cresols, 2,4-dimethylphenol, brenzcatechine, syringol, eugenol, vanilline and guaiacol) gave negative results when they were tested for mutagenicity at five concentrations up to 5000 micrograms/plate, with and without S-9 mix, using five strains of S. typhimurium. Even when phenol was further investigated in a variety of test conditions, no induction of his+ revertants was observed. When smokehouse smoke was condensed and fractionated the majority of the various phenolic fractions also gave negative results when tested at five concentrations using five strains of S. typhimurium. However there was a slight increase in the number of revertants in a few cases. The presence in the phenolic fractions of very small amounts of mutagenic impurities, the nature of which needs further investigation, cannot be excluded. These results support the further development of non-hazardous smoke-aroma preparations, based on the phenolic components of smokehouse smoke.

  13. Interactive lethal and mutagenic effects of ultraviolet light and bleomycin in yeast: synergism or antagonism?

    PubMed

    Lillo, O L; Severgnini, A A; Nunes, E M

    1997-11-01

    The mutagenic interactions of ultraviolet light and bleomycin in haploid populations of Saccharomyces cerevisiae were analyzed. Survival and mutation frequency as a function of different bleomycin concentrations after one conditioning dose of UV radiation were determined. Furthermore, corresponding interaction functions and sensitization factors were calculated. A synergistic interaction between UV light and bleomycin was shown for both lethal and mutagenic events when the cells were in nutrient broth during the treatments. Conversely, the interaction between UV light and bleomycin was antagonistic when the cells were in deionized water during the treatment. The magnitude of lethal and mutagenic interactions depends on dose, and thus presumably on the number of lesions. The observed interactions between UV light and bleomycin suggest that the mechanism that is most likely involved is the induction of repair systems with different error probabilities during the delay of cell division.

  14. [Mutagenic evaluation of the urine of rats treated with oils implicated in the toxic oil syndrome using bacterial tests].

    PubMed

    Barrueco, C; Sladek, F; Canga, C; Valcarce, E; de la Peña, E; Alia, M; Laborda, E

    1983-01-01

    The mutagenic activity of the urine of pregnant rats treated with toxic oil syndrome-related rape seed oil or with edible oil was evaluated by means of the Ames and Green tests. It was found that the urine of the pregnant rats treated with "Jen" oil, that was related to the toxic oil syndrome, was mutagenic.

  15. Long-range transport of mutagens and other air pollutants from mainland East Asia to western Japan.

    PubMed

    Coulibaly, Souleymane; Minami, Hiroki; Abe, Maho; Hasei, Tomohiro; Oro, Tadashi; Funasaka, Kunihiro; Asakawa, Daichi; Watanabe, Masanari; Honda, Naoko; Wakabayashi, Keiji; Watanabe, Tetsushi

    2015-01-01

    Asian dust events, transport of dust particles from arid and semi-arid areas in China and Mongolia to the east by prevailing westerlies, are often observed in Japan in spring. In recent decades, consumption of fossil fuels has markedly increased in mainland East Asia with rapid economic growth, and severe air pollution has occurred. A part of air pollutants including mutagens, such as polycyclic aromatic hydrocarbons (PAHs), generated in mainland East Asia are thought to be transported to Japan by the prevailing westerlies, like Asian dust, and winter monsoon. The objective of this study was to clarify the long-range transport of mutagens and other air pollutants in East Asia. Thus, we collected total suspended particles (TSP) at a rural town in western Japan, namely, Yurihama in Tottori Prefecture, for 1 year (June 2012-May 2013), and investigated their chemical constituents and mutagenicity. Many TSP collected from January to March showed high mutagenicity toward Salmonella typhimurium YG1024 with and without S9 mix, and high levels of lead (Pb) and sulfate ions (SO4 (2-)), which are indicators of transboundary air pollutions from mainland East Asia, were detected in those TSP. A large amount of iron, which is an indicator of sand, was found in highly mutagenic TSP collected in March, but not in TSP collected in January and February. High levels of PAHs were detected in highly mutagenic TSP collected from January to March. The ratios of the concentration of fluoranthene to those of fluoranthene and pyrene suggested that the main source of PAHs in TSP collected in winter and spring was coal and biomass combustion. Backward trajectories of air masses on days when high levels of mutagenicity were found indicated that these air masses had traveled from eastern or northern China to Yurihama. These results suggest that high levels of mutagens were transported from mainland East Asia to western Japan, and this transportation accompanied Asian dust in March, but not in

  16. Mutagenic effect of freezing on nuclear DNA of Saccharomyces cerevisiae.

    PubMed

    Todorova, T; Pesheva, M; Stamenova, R; Dimitrov, M; Venkov, P

    2012-05-01

    Although fragmentation of DNA has been observed in cells undergoing freezing procedures, a mutagenic effect of sub-zero temperature treatment has not been proved by induction and isolation of mutants in nuclear DNA (nDNA). In this communication we supply evidence for mutagenicity of freezing on nDNA of Saccharomyces cerevisiae cells. In the absence of cryoprotectors, cooling for 2 h at +4°C and freezing for 1 h at -10°C and 16 h at -20°C, with a cooling rate of 3°C/min, resulted in induction of frame-shift and reverse mutations in microsatellite and coding regions of nDNA. The sub-zero temperature exposure also has a strong recombinogenic effect, evidenced by induction of gene-conversion and crossing-over events. Freezing induces mutations and enhances recombination with a frequency equal to or higher than that of methylmethanesulphonate at comparable survival rates. The signals for the appearance of nDNA lesions induced by freezing are detected and transduced by the DNA damage pathway. Extracellular cryoprotectors did not prevent the mutagenic effect of freezing, while accumulation of trehalose inside cells reduced nDNA cryodamage. Freezing of cells is accompanied by generation of high ROS levels, and the oxidative stress raised during the freeze-thaw process is the most likely reason for the DNA damaging effect. Experiments with mitochondrial rho⁻ mutants or scavengers of ROS indicated that mutagenic and recombinogenic effects of sub-zero temperatures can be decreased but not eliminated by reduction of ROS level. The complete protection against cryodamage in nDNA required simultaneous usage of intracellular cryoprotector and ROS scavenger during the freeze-thaw process. Copyright © 2012 John Wiley & Sons, Ltd.

  17. Effects of human placental S9 and induced rat liver S9 on the mutagenicity of drinking waters processed from humus-rich surface waters

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vartiainen, T.; Lampelo, S.

    The mutagenicity of chlorinated drinking waters processed from humus-rich surface waters has been shown to be very high. The effect of placental S9 on the mutagenicity of drinking waters has not been studied previously. The purpose of this study was to compare the effects of human placental and rat liver microsomal fractions on the mutagenicity of drinking waters processed from humus-rich surface waters. The samples of 34 drinking and two raw waters from 26 localities in Finland were tested for mutagenicity in Ames Salmonella typhimurium tester strain TA100 with and without metabolic activations. Between the drinking water samples, clear differencesmore » were recorded in the presence of placental and rat liver S9, suggesting different mutagens in the drinking waters. Rat liver S9 decreased the mutagenicities of drinking water concentrates, but placental S9 increased, decreased, or had no effect. It is not known if placental mutagenicity enhancing system might cause any health hazard to a developing fetus.« less

  18. Biodegradability, toxicity and mutagenicity of detergents: Integrated experimental evaluations.

    PubMed

    Pedrazzani, Roberta; Ceretti, Elisabetta; Zerbini, Ilaria; Casale, Rosario; Gozio, Eleonora; Bertanza, Giorgio; Gelatti, Umberto; Donato, Francesco; Feretti, Donatella

    2012-10-01

    The widespread use of detergents has raised concern with regard to the environmental pollution caused by their active ingredients, which are biorefractory, toxic and persistent. Since detergents are complex mixtures of different substances, in which synergistic effects may occur, we aimed to assess the mutagenicity of different detergent formulations, taking into account aquatic toxicity and ready biodegradability. We performed a ready biodegradability test (OECD 301 F), Daphnia magna and Vibrio fischeri toxicity tests, and mutagenicity tests (Salmonella/microsome test, Allium cepa test and comet assay). Six detergent formulations were examined, 3 pre-manufacture and 3 commercially available. All detergents presented ready biodegradability. EC50 values varied for all products, according to the marker organism used, but were always higher than the more stringent value considered for aquatic toxicity assessment (V. fischeri 10-60 mg/L; D. magna 25-300 mg/L; A. cepa 250-2000 mg/L). None of the detergents caused mutations in bacteria. However, one commercial ecolabelled product induced an increase in micronucleus frequency in A. cepa root cells. All pre-manufacture detergents and one commercial one, which gave negative results in the Ames and A. cepa tests, induced DNA damage in human leukocytes. A more accurate evaluation of the environmental impact of complex mixtures such as detergents requires a battery of tests to describe degradation, as well as toxicological and mutagenic features. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Mutagenicity and Lung Toxicity of Smoldering vs. Flaming Emissions from Various Biomass Fuels: Implications for Health Effects from Wildland Fires.

    PubMed

    Kim, Yong Ho; Warren, Sarah H; Krantz, Q Todd; King, Charly; Jaskot, Richard; Preston, William T; George, Barbara J; Hays, Michael D; Landis, Matthew S; Higuchi, Mark; DeMarini, David M; Gilmour, M Ian

    2018-01-24

    The increasing size and frequency of wildland fires are leading to greater potential for cardiopulmonary disease and cancer in exposed populations; however, little is known about how the types of fuel and combustion phases affect these adverse outcomes. We evaluated the mutagenicity and lung toxicity of particulate matter (PM) from flaming vs. smoldering phases of five biomass fuels, and compared results by equal mass or emission factors (EFs) derived from amount of fuel consumed. A quartz-tube furnace coupled to a multistage cryotrap was employed to collect smoke condensate from flaming and smoldering combustion of red oak, peat, pine needles, pine, and eucalyptus. Samples were analyzed chemically and assessed for acute lung toxicity in mice and mutagenicity in Salmonella . The average combustion efficiency was 73 and 98% for the smoldering and flaming phases, respectively. On an equal mass basis, PM from eucalyptus and peat burned under flaming conditions induced significant lung toxicity potencies (neutrophil/mass of PM) compared to smoldering PM, whereas high levels of mutagenicity potencies were observed for flaming pine and peat PM compared to smoldering PM. When effects were adjusted for EF, the smoldering eucalyptus PM had the highest lung toxicity EF (neutrophil/mass of fuel burned), whereas smoldering pine and pine needles had the highest mutagenicity EF. These latter values were approximately 5, 10, and 30 times greater than those reported for open burning of agricultural plastic, woodburning cookstoves, and some municipal waste combustors, respectively. PM from different fuels and combustion phases have appreciable differences in lung toxic and mutagenic potency, and on a mass basis, flaming samples are more active, whereas smoldering samples have greater effect when EFs are taken into account. Knowledge of the differential toxicity of biomass emissions will contribute to more accurate hazard assessment of biomass smoke exposures. https://doi.org/10

  20. MUTAGENIC AND CLASTOGENIC PROPERTIES OF 3-CHLORO-4-(DICHLOROMETHYL)-5-HYDROXY-2(5H)-FURANONE: A POTENT BACTERIAL MUTAGEN IN DRINKING WATER

    EPA Science Inventory

    3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) was found to be a direct-acting mutagen in the Ames test for strains TA1535, TA1538, TA92, TA97, TA98, TA100 and TA102. The highest mutagenic response (approximately 13,000 revertants/nmol) was seen in strain TA100. The TA...

  1. AZO DYES ARE MAJOR CONTRIBUTORS TO THE MUTAGENIC ACTIVITY DETECTED IN THE CRISTAIS RIVER WATERS

    EPA Science Inventory

    To determine if compounds from a dye processing plant were contributing to the mutagenicity repeatedly found in the Cristais River, Sao Paulo, Brazil, we chemically characterized the treated industrial effluent, raw and treated water, and the sludge produced by a Drinking Water T...

  2. Improved method for mutagenicity testing of gaseous compounds by using a gas sampling bag.

    PubMed

    Araki, A; Noguchi, T; Kato, F; Matsushima, T

    1994-05-01

    A simple and safety gas exposure method was developed using a gas sampling bag as an exposure vessel and a preparation vessel of diluted gas. The gas exposure conditions such as amount of S9 in the plate, volume of gas for the plate, amount of top agar, exposure period and exposure temperature were examined by mutagenicity testing of 1,3-butadiene using the gas sampling bag. Mutagenicity tests of 14 compounds and 1,3-butadiene on S. typhimurium TA98, TA100, TA1535 and TA1537, and E. coli WP2 uvrA were also examined by the developed gas exposure method. 1,3-Butadiene, propyne (methyl acetylene), monochlorodifluoromethane, ethylchloride, diborane and silane were mutagenic. 1-Butene, 2-butene, 2-methylpropene, methyl vinyl ether, trichlorofluoromethane, dichlorodifluoromethane, 1,2-dichloro-1,1,2,2-tetrafluoroethane, 1,1-difluoroethane and phosphine were not mutagenic on S. typhimurium TA98, TA100, TA1535 and TA1537, and E. coli WP2 uvrA with or without metabolic activation. These results were compatible with a previous report, and this developed method has the advantage that it can be tested easily and safely for combustible and self-combustible substances such as 1,3-butadiene and silane.

  3. Investigation of toxicity and mutagenicity of cold atmospheric argon plasma.

    PubMed

    Maisch, T; Bosserhoff, A K; Unger, P; Heider, J; Shimizu, T; Zimmermann, J L; Morfill, G E; Landthaler, M; Karrer, S

    2017-04-01

    Cold atmospheric argon plasma is recognized as a new contact free approach for the decrease of bacterial load on chronic wounds in patients. So far very limited data are available on its toxicity and mutagenicity on eukaryotic cells. Thus, the toxic/mutagenic potential of cold atmospheric argon plasma using the MicroPlaSter β ® , which has been used efficiently in humans treating chronic and acute wounds, was investigated using the XTT assay in keratinocytes and fibroblasts and the HGPRT (hypoxanthine guanine phosphoribosyl transferase) assay with V79 Chinese hamster cells. The tested clinical parameter of a 2 min cold atmospheric argon plasma treatment revealed no relevant toxicity on keratinocytes (viability: 76% ± 0.17%) and on fibroblasts (viability: 81.8 ± 0.10) after 72 hr as compared to the untreated controls. No mutagenicity was detected in the HGPRT assay with V79 cells even after repetitive CAP treatments of 2-10 min every 24 hr for up to 5 days. In contrast, UV-C irradiation of V79 cells, used as a positive control in the HGPRT test, led to DNA damage and mutagenic effects. Our findings indicate that cold atmospheric plasma using the MicroPlaSter β ® shows negligible effects on keratinocytes and fibroblasts but no mutagenic potential in the HGPRT assay, indicating a new contact free safe technology. Environ. Mol. Mutagen. 58:172-177, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. Cytotoxicity and mutagenicity of fluoxetine hydrochloride (Prozac), with or without vitamins A and C, in plant and animal model systems.

    PubMed

    Düsman, E; Almeida, I V; Mariucci, R G; Mantovani, M S; Vicentini, V E P

    2014-01-28

    Fluoxetine, commonly known as Prozac, is the first representative of the so-called new generation of antidepressants that promise efficacy, with few side effects, against deep depression, nervous bulimia, and anxiety. As there is a growing number of people suffering from anxiety and depression; consequently, the use of fluoxetine is also increasing. Verifying absence of drug effects such as cytotoxicity or mutagenicity is of great importance. Certain vitamins, such as vitamin A (retinol, retinoids) and vitamin C (ascorbic acid) protect and are extremely active against mutagens. We evaluated the cytotoxic and mutagenic activity of fluoxetine, with and without concomitant administration of vitamin A or C, in Allium cepa meristem cells and Wistar rat bone marrow cells. The A. cepa meristem cells showed fluoxetine cytotoxicity; concomitant treatment with vitamin A or C proved non-protective. Treatment of Wistar rats with fluoxetine intraperitoneally or via gavage did not affect cell division or cause clastogenic effects. Vitamin A and C did not affect the cytotoxicity or mutagenicity of fluoxetine in the rat cells.

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

    EPA Science Inventory

    The genotoxicity of ambient outdoor air, a review: Salmonella mutagenicity

    Abstract
    Mutagens
    in urban air pollution come from anthropogenic sources (especially combustion sources) and are products of airborne chemical reactions. Bacterial mutation tests have been used ...

  6. Merging Applicability Domains for in Silico Assessment of Chemical Mutagenicity

    DTIC Science & Technology

    2014-02-04

    molecular fingerprints as descriptors for developing quantitative structure−activity relationship ( QSAR ) models and defining applicability domains with...used to define and quantify an applicability domain for either method. The importance of using applicability domains in QSAR modeling cannot be...domain from roughly 80% to 90%. These results indicated that the proposed QSAR protocol constituted a highly robust chemical mutagenicity prediction

  7. METHODS FOR THE SPIRAL SALMONELLA MUTAGENICITY ASSAY INCLUDING SPECIALIZED APPLICATIONS

    EPA Science Inventory

    ABSTRACT

    An automated approach to bacterial mutagenicity testing--the spiral Salmonella assay--was developed to simplify testing and to reduce the labor and materials required to generate dose-responsive mutagenicity information. This document provides the reader with an ...

  8. Mouse mutants from chemically mutagenized embryonic stem cells

    PubMed Central

    Munroe, Robert J.; Bergstrom, Rebecca A.; Zheng, Qing Yin; Libby, Brian; Smith, Richard; John, Simon W.M.; Schimenti, Kerry J.; Browning, Victoria L.; Schimenti, John C.

    2010-01-01

    The drive to characterize functions of human genes on a global scale has stimulated interest in large-scale generation of mouse mutants. Conventional germ-cell mutagenesis with N-ethyl-N-nitrosourea (ENU) is compromised by an inability to monitor mutation efficiency, strain1 and interlocus2 variation in mutation induction, and extensive husbandry requirements. To overcome these obstacles and develop new methods for generating mouse mutants, we devised protocols to generate germline chi-maeric mice from embryonic stem (ES) cells heavily mutagenized with ethylmethanesulphonate (EMS). Germline chimaeras were derived from cultures that underwent a mutation rate of up to 1 in 1,200 at the Hprt locus (encoding hypoxanthine guanine phosphoribosyl transferase). The spectrum of mutations induced by EMS and the frameshift mutagen ICR191 was consistent with that observed in other mammalian cells. Chimaeras derived from ES cells treated with EMS transmitted mutations affecting several processes, including limb development, hair growth, hearing and gametogenesis. This technology affords several advantages over traditional mutagenesis, including the ability to conduct shortened breeding schemes and to screen for mutant phenotypes directly in ES cells or their differentiated derivatives. PMID:10700192

  9. Antimicrobial and mutagenic activity of some carbono- and thiocarbonohydrazone ligands and their copper(II), iron(II) and zinc(II) complexes.

    PubMed

    Bacchi, A; Carcelli, M; Pelagatti, P; Pelizzi, C; Pelizzi, G; Zani, F

    1999-06-15

    Several mono- and bis- carbono- and thiocarbonohydrazone ligands have been synthesised and characterised; the X-ray diffraction analysis of bis(phenyl 2-pyridyl ketone) thiocarbonohydrazone is reported. The coordinating properties of the ligands have been studied towards Cu(II), Fe(II), and Zn(II) salts. The ligands and the metal complexes were tested in vitro against Gram positive and Gram negative bacteria, yeasts and moulds. In general, the bisthiocarbonohydrazones possess the best antimicrobial properties and Gram positive bacteria are the most sensitive microorganisms. Bis(ethyl 2-pyridyl ketone) thiocarbonohydrazone, bis(butyl 2-pyridyl ketone)thiocarbonohydrazone and Cu(H2nft)Cl2 (H2nft, bis(5-nitrofuraldehyde)thiocarbonohydrazone) reveal a strong activity with minimum inhibitory concentrations of 0.7 microgram ml-1 against Bacillus subtilis and of 3 micrograms ml-1 against Staphylococcus aureus. Cu(II) complexes are more effective than Fe(II) and Zn(II) ones. All bisthiocarbono- and carbonohydrazones are devoid of mutagenic properties, with the exception of the compounds derived from 5-nitrofuraldehyde. On the contrary a weak mutagenicity, that disappears in the copper complexes, is exhibited by monosubstituted thiocarbonohydrazones.

  10. Pointing to potential reference areas to assess soil mutagenicity.

    PubMed

    Meyer, D D; Da Silva, F M R; Souza, J W M; Pohren, R S; Rocha, J A V; Vargas, V M F

    2015-04-01

    Several have been performed to evaluate the mutagenicity of soil samples in urban and industrial areas. The use of uncontaminated reference areas has been an obstacle to the study of environmental mutagenesis. The study aimed to indicate a methodology to define reference areas in studies of environmental contamination based on "Ambient Background Concentration" of metallic elements associated with the Salmonella/microsome assay. We looked at three potential reference areas, two of them close by the industrial sources of contamination (São Jerônimo reference, near the coal-fired power plant, and Triunfo reference, near the wood preservative plant), but not directly influenced by them and an area located inside a protected area (Itapuã reference). We also carried out chemical analyses of some metals to plot the metal profile of these potential reference areas and define basal levels of these metals in the soils. After examining the mutagenicity of the inorganic extracts using strains TA98, TA97a, and TA100, in the presence and absence of S9 mix, we indicated the São Jerônimo reference and the Itapuã reference as two sites that could be used in future studies of mutagenicity of soils in southern Brazil. The association between a mutagenicity bioassay and the "Ambient Background Concentration" seems to be a useful method to indicate the reference areas in studies of contamination by environmental mutagens, where these results were corroborated by canonical correspondence analysis.

  11. Short-term bioassay of complex organic mixtures. Part II. Mutagenicity testing

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Epler, J.L.; Clark, B.R.; Ho, C.

    1978-01-01

    The feasibility of using short-term mutagenicity assays to predict the potential biohazard of various crude and complex test materials has been examined in a coupled chemical and biological approach. The principal focus of the research has involved the preliminary chemical characterizatiion and preparation for bioassay, followed by testing in the Salmonella histidine reversion assay system. The mutagenicity tests are intended to act as predictors of profound long-range health effects such as mutagenesis and/or carcinogenesis; act as a mechanism to rapidly isolate and identify a hazardous agent in a complex mixture; and function as a measure of biological activity correlating baselinemore » data with changes in process conditions. Since complex mixtures can be fractionated and approached in these short-term assays, information reflecting on the actual compounds responsible for the biological effect may be accumulated.« less

  12. Use of a Salmonella microsuspension bioassay to detect the mutagenicity of munitions compounds at low concentrations.

    PubMed

    George, S E; Huggins-Clark, G; Brooks, L R

    2001-01-25

    Past production and handling of munitions has resulted in soil contamination at various military facilities. Depending on the concentrations present, these soils pose both a reactivity and toxicity hazard and the potential for groundwater contamination. Many munitions-related chemicals have been examined for mutagenicity in the Ames test, but because the metabolites may be present in low environmental concentrations, a more sensitive method is needed to elucidate the associated mutagenicity. RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine), TNT (2,4,6-trinitrotoluene), tetryl (N-methyl-N-2,4,6-tetranitroaniline), TNB (1,3,5-trinitrobenzene) and metabolites were examined for mutagenicity in a microsuspension modification of the Salmonella histidine reversion assay with and without metabolic activation. TNB and tetryl were positive in TA98 (32.5, 5.2revertants/nmole) and TA100 (7.4, 9.5revertants/nmole) without metabolic activation and were more potent than TNT (TA98, 0.3revertants/nmole; TA100, 2.4revertants/nmole). With the exception of the tetranitroazoxytoluene derivatives, TNT metabolites were less mutagenic than TNT. RDX and two metabolites were negative in both strains, however, hexahydro-1,3,5-trinitroso-1,3,5-triazine was positive in TA100 with and without S9. Microsuspension bioassay results tend to correlate well with published Ames test data, however, there are discrepancies among the published data sets and the microsuspension assay results.

  13. Mutagenicity of comfrey (Symphytum Officinale) in rat liver

    PubMed Central

    Mei, N; Guo, L; Fu, P P; Heflich, R H; Chen, T

    2005-01-01

    Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and herbal remedy by humans. In order to evaluate the mechanisms underlying its carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and the types of mutations induced by comfrey suggest that its tumorigenicity results from the genotoxicity of pyrrolizidine alkaloids in the plant. PMID:15726100

  14. Cytotoxicity and mutagenicity studies on migration extracts from nanocomposites with potential use in food packaging.

    PubMed

    Maisanaba, Sara; Pichardo, Silvia; Jordá-Beneyto, María; Aucejo, Susana; Cameán, Ana M; Jos, Ángeles

    2014-04-01

    Clays are used in the food packaging industry to obtain nanocomposites. The use of these new materials is a concern, because they could reach consumers by oral exposure through possible migration, and potential toxic effects could be derived. In the present study, several in vitro basal cytotoxicity and mutagenicity tests on migration extracts obtained from a nanocomposite material with poly (lactic) acid (PLA) and two modified clays, Clay1 and Clay2, are shown. Migration extracts in distilled water showed values of 0.1 ± 0.2mg/dm(2) in all samples. Also, the content of characteristic metals of the clays structure (Al, Ca, Mg, Fe, Si) was studied and no statistical differences were observed. For the cytotoxicity assays, the human intestinal Caco-2 and human liver HepG2 cells were selected. Cells were exposed to concentrations between 2.5% and 100% extracts determining three different biomarkers of cellular viability. No significant differences were observed in the cytotoxicity assays. Finally, mutagenicity was evaluated by the Ames test and resulted in the absence of mutagenic response at all the concentrations assayed. Taking in account all above mentioned, these new materials show a good profile for their use in food packaging although further research is still needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Morphology Dependent Photocatalytic Activity of α-MoO3 Nanostructures Towards Mutagenic Acridine Orange Dye.

    PubMed

    2015-06-01

    The morphological evolutions of orthorhombic molybdenum oxide nanostructures with high crystalline nature have been successfully synthesized by combining low-temperature sol-gel and annealing processes. Strong influence of gelation temperature is a factor facilitated to control the material morphology. Morphological transformations like nanospheres, nanoplatelets, mixtures of hexagonal platelets, and one-dimensional nanobars were obtained. The possible morphological formation mechanism has been proposed as a self-assemble process of nucleation and a mechanism for particle growth by Ostwald ripening. The as-prepared nanostructures were recognized as photocatalysts for the degradation of Acridine Orange under Ultra Violet light. The obtained mixed morphology (hexagonal nanoplatelets and nanobars) showed a high photocatalytic property to degrade mutagenic Acridine Orange dye. Moreover, they could be easily recycled without changing the photocatalytic activity due to their 1-Dimensional and 2-Dimensional nanostructure property.

  16. Thai generic-brand dry canine foods: mutagenicity and the effects of feeding in vivo and in vitro.

    PubMed

    Khuntamoon, Tanyalak; Thepouyporn, Apanchanid; Kaewprasert, Sarunya; Prangthip, Pattaneeya; Pooudoung, Somchai; Chaisri, Urai; Maneesai, Phudit; Kwanbunjan, Karunee

    2016-01-20

    The commercial pet-food industry and the market value of the pet industry have increased. Most owners are concerned about their pets' health, and prefer commercial pet foods as their regular diet. This study thus aimed to determine whether a selection of local generic-brand dry canine foods had any potential to promote chronic disease. Five local, generic-brand, dry canine foods were studied for potential mutagenicity; the effects of long-term consumption were also observed in rats. All canine foods were extracted with distilled water and absolute ethanol. The Ames test was used to detect short-term genetic damage, using Salmonella typhimurium tester strains TA98 and TA100. Simultaneously, the long-term effects were studied in an animal model by observing rats fed with these canine foods, compared with normal rat food, for a period of 15 weeks. Using the water extracts, all dry canine foods studied showed considerable mutagenic effects on the tester strains. One brand affected both tester strains, whereas 3 showed positive to TA98, and one to TA100. With the absolute ethanol extract, three of the five brands had a considerable mutagenic effect on TA98, and another affected TA100. In the long-term test, all rats remained alive until the end of the experiment, exhibited no apparent signs of toxicity or serious illness, and maintained normal bodyweight and weight gain. Serum blood biochemistry and hematological parameters in canine food-fed rats showed some negative effects. Correspondingly, histopathological investigation of their liver and kidneys showed deterioration. Mutagenic potential and the negative potential health impacts were observed in all local-brand dry canine foods tested.

  17. Mutagenicity of chromium picolinate and its components in Salmonella typhimurium and L5178Y mouse lymphoma cells.

    PubMed

    Whittaker, Paul; San, Richard H C; Clarke, Jane J; Seifried, Harold E; Dunkel, Virginia C

    2005-11-01

    Chromium picolinate is one of the most commonly used chromium dietary supplements available in the United States, and it has been marketed to consumers for use in weight loss, increasing muscle mass, and lowering serum cholesterol. Chromium picolinate is a synthetic compound that provides a bioavailable form of Cr(III) that is absorbed better than dietary chromium. However, there are several reports that it can have adverse effects. In order to study the mechanism of observed cellular toxicity and mutagenicity, chromium picolinate and its component compounds, chromium (III) chloride and picolinic acid, were evaluated in Salmonella typhimurium and L5178Y mouse lymphoma cells. Neither chromium picolinate nor chromium chloride induced a mutagenic response in S. typhimurium. However, in the L5178Y mouse lymphoma mutation assay, chromium picolinate induced mutagenic responses without and with the addition of S9.

  18. Mutagenic effect of freezing on mitochondrial DNA of Saccharomyces cerevisiae.

    PubMed

    Stoycheva, T; Venkov, P; Tsvetkov, Ts

    2007-06-01

    Although suggested in some studies, the mutagenic effect of freezing has not been proved by induction and isolation of mutants. Using a well-defined genetic model, we supply in this communication evidence for the mutagenic effect of freezing on mitochondrial DNA (mtDNA) of the yeast Saccharomyces cerevisiae. The cooling for 2 h at +4 degrees C, followed by freezing for 1 h at -10 degrees C and 16 h at -20 degrees C resulted in induction of respiratory mutations. The immediate freezing in liquid nitrogen was without mutagenic effect. The study of the stepwise procedure showed that the induction of respiratory mutants takes place during the freezing at -10 and -20 degrees C of cells pre-cooled at +4 degrees C. The genetic crosses of freeze-induced mutants evidenced their mitochondrial rho- origin. The freeze-induced rho- mutants are most likely free of simultaneous nuclear mutations. The extracellular presence of cryoprotectants did not prevent the mutagenic effect of freezing while accumulation of cryoprotectors inside cells completely escaped mtDNA from cryodamage. Although the results obtained favor the notion that the mutagenic effect of freezing on yeast mtDNA is due to formation and growth of intracellular ice crystals, other reasons, such as impairment of mtDNA replication or elevated levels of ROS production are discussed as possible explanations of the mutagenic effect of freezing. It is concluded that: (i) freezing can be used as a method for isolation of mitochondrial mutants in S. cerevisiae and (ii) given the substantial development in cryopreservation of cells and tissues, special precautions should be made to avoid mtDNA damage during the cryopreservation procedures.

  19. In vitro genotoxicity of neutral red after photo-activation and metabolic activation in the Ames test, the micronucleus test and the comet assay.

    PubMed

    Guérard, Melanie; Zeller, Andreas; Singer, Thomas; Gocke, Elmar

    2012-07-04

    Neutral red (Nr) is relatively non-toxic and is widely used as indicator dye in many biological test systems. It absorbs visible light and is known to act as a photosensitizer, involving the generation of reactive oxygen species (type-I reaction) and singlet oxygen (type-II reaction). The mutagenicity of Nr was determined in the Ames test (with Salmonella typhimurium strains TA1535, TA97, TA98, TA98NR, TA100, and TA102) with and without metabolic activation, and with and without photo-activation on agar plates. Similarly to the situation following metabolic activation, photo-mutagenicity of Nr was seen with all Salmonella strains tested, albeit with different effects between these strains. To our knowledge, Nr is the only photo-mutagen showing such a broad action. Since the effects are also observed in strains not known to be responsive to ROS, this indicates that ROS production is not the sole mode of action that leads to photo-genotoxicity. The reactive species produced by irradiation are short-lived as pre-irradiation of an Nr solution did not produce mutagenic effects when added to the bacteria. In addition, mutagenicity in TA98 following irradiation was stronger than in the nitroreductase-deficient strain TA98NR, indicating that nitro derivatives that are transformed by bacterial nitroreductase to hydroxylamines appear to play a role in the photo-mutagenicity of Nr. Photo-genotoxicity of Nr was further investigated in the comet assay and micronucleus test in L5178Y cells. Concentration-dependent increases in primary DNA damage and in the frequency of micronuclei were observed after irradiation. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Personal thoughts on the future of the Environmental Mutagen Society.

    PubMed

    Brusick, D

    1994-01-01

    The Environmental Mutagen Society (EMS) was one of the first professional scientific societies organized to respond to an environmental concern. The threat of environmental pollution stimulated the formation of the organization in 1969. The Society's mission was to create a forum for discussion of methods and strategies to deal with mutagenic agents formed and/or released into the environment. During the past 25 years, EMS has provided a forum for innovation and scientific discussions. The Environmental Mutagen Society, and, in particular, its applied role in genetic toxicology, has had a profound positive impact on many disciplines in toxicology and safety assessment (i.e., carcinogenesis and in vitro alternatives.

  1. Review: putative mutagens and carcinogens in foods. VII. Genetic toxicology of the diet

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hatch, F.T.; MacGregor, J.T.; Zeiger, E.

    Individual reviews of approximately 30 papers presented at the Fourth International Conference on Environmental Mutagens are presented in this report. Topics covered include diet in cancer epidemiology; cooked and processed food as a source of mutagens and carcinogens; natural genotoxins in plants and beverages; mutagens within the gastrointestinal tract; and modulation of mutagenesis and carcinogenesis.

  2. Evaluation of genotoxic and anti-mutagenic properties of cleistanthin A and cleistanthoside A tetraacetate.

    PubMed

    Himakoun, Lakana; Tuchinda, Patoomratana; Puchadapirom, Pranom; Tammasakchai, Ratigon; Leardkamolkarn, Vijittra

    2011-01-01

    Cleistanthin A (CleinA) and cleistanthoside A (CleisA) isolated from plant Phyllanthus taxodiifolius Beille have previously shown potent anticancer effects. To promote their medicinal benefits, CleisA was modified to cleistanthoside A tetraacetate (CleisTA) and evaluated for genotoxic and anti-mutagenic properties in comparison with CleinA. Both compounds showed no significant mutagenic activity to S. typhimulium bacteria and no cytotoxic effect to normal mammalian cells. The non genotoxic effect of CleinA was further confirmed by un-alteration of cytokinesis-block proliferation index (CBPI) and micronucleus (MN) frequency assays in Chinese hamster lung fibroblast (V79) cells, and of CleisTA was confirmed by un-changes of human peripheral blood lymphocytes (HPBL) chromosomal structure assay. Moreover, the metabolic form of CleinA efficiently demonstrated cytostasis effect to V79 cell and prevented mutagen induced Salmonella TA98 and TA100 reversion, whereas both metabolic and non-metabolic forms of CleisTA reduced HPBL mitotic index (%M.I) in a concentration-dependent relationship. The results support CleinA and CleisTA as the new lead compounds for anti-cancer drug development.

  3. REVIEW OF THE SALMONELLA TYPHIMURIUM MUTAGENICITY OF BENZIDINE, BENZIDINE ANALOGUES, AND BENZIDINE-BASED DYES

    EPA Science Inventory

    The mutagenicity of benzidine analogues (including benzidine-based dyes) was reviewed with a primary emphasis on evaluating results of the Salmonella/microsome mutagenicity assay. Many of these amines are mutagenic in tester strains TA98 and TA100 but require exogenous mammalian ...

  4. Are All Ames Strains in the OECD Mutagenicity Test Guideline 471 Useful and Necessary? An Analysis of Large Mutagenicity Data Sets for the IWGT.

    EPA Science Inventory

    Are All Ames Strains in the OECD Mutagenicity Test Guideline 471 Useful and Necessary? An Analysis of Large Mutagenicity Data Sets for the IWGT R. Williams1, D.M. DeMarini2, L.F. Stankowski Jr.3, E. Zeiger4, K.P. Cross5 1Lhasa, LTD, Leeds, UK 2U.S. EPA, RTP, NC 3Charles River L...

  5. Mutagen-induced fetal anomalies and death following treatment of females within hours after mating.

    PubMed

    Generoso, W M; Rutledge, J C; Cain, K T; Hughes, L A; Downing, D J

    1988-05-01

    In an earlier study (Generoso et al., 1987), it was observed that the mutagen, ethylene oxide (EtO), produced remarkable increases in the incidence of developmental abnormalities and death of fetuses when early zygotic stages were exposed. This is a major finding in experimental induction of embryopathy, implicating genetic damage to the zygotes as the likely cause. In the subsequent study reported here, 3 other mutagens--ethyl methanesulfonate (EMS), ethyl nitrosourea (ENU), and triethylene melamine (TEM), were studied for embryopathic effects following exposure of dictyate oocytes, prefertilization oviducal eggs and sperm, early pronuclear zygotes, zygotes undergoing pronuclear DNA synthesis, and two-cell embryos. All 4 mutagens produced developmental abnormalities among living fetuses following exposure of early pronuclear zygotes (the only stage studied for this endpoint in this report). With respect to stage specificity and gestational timing of death of conceptuses, EMS and EtO on one hand and ENU and TEM on the other, are very similar to one another. EMS, like EtO, produced a high incidence of midgestation and late fetal deaths only in prefertilization oviducal eggs and sperm and in early pronuclear eggs. In contrast, ENU and TEM produced high losses of conceptuses in all postmating stages studied but death occurred primarily prior to or around the time of implantation. Thus, the frequency of induction and the expression of embryopathy, which ranged from early embryonic preimplantation and late fetal deaths to subtle fetal anomalies, are dependent upon the stage exposed and the mutagen used.

  6. Mutagenicity of streptozotocin and several other nitrosourea compounds in Salmonella typhimurium.

    PubMed

    Zimmer, D M; Bhuyan, B K

    1976-11-01

    The following nitrosourea compounds were compared for their ability to induce mutation (to histidine independence) in the histidine-requiring auxotroph Salmonella typhimurium his G46: MNU, streptozotocin (SZ, streptozocin) and its analogs SZA1 and SZA2, and the antitumor drugs BCNU, CCNU and DCNU. At equitoxic doses SZ, SZA1, SZA2 and MNU were almost equally mutagenic causing 150, 42, 140 and 170 mutants/106 survivors at 20% lethal dose (ID20) ALTHOUGH, ON A WIEGHT BASIS, SZ was the most mutagenic of all the compounds tested. At ID20 BCNU, CCNU and DCNU gave about 0.5 mutants/106 survivors. Our results show that these nitrosoureas, in common with many other drugs (such as cyclophosphamide, daunomycin, etc.) used in cancer chemotherapy, are highly mutagenic. The implication of our results in the screening of drugs for their mutagenicity to man is discussed.

  7. Using Saccharomyces cerevisiae to test the mutagenicity of household compounds: an open ended hypothesis-driven teaching lab.

    PubMed

    Marshall, Pamela A

    2007-01-01

    In our Fundamentals of Genetics lab, students perform a wide variety of labs to reinforce and extend the topics covered in lecture. I developed an active-learning lab to augment the lecture topic of mutagenesis. In this lab exercise, students determine if a compound they bring from home is a mutagen. Students are required to read extensive background material, perform research to find a potential mutagen to test, develop a hypothesis, and bring to the lab their own suspected mutagen. This lab uses a specially developed strain of Saccharomyces cerevisiae, D7, to determine if a compound is a mutagen. Mutagenesis of the D7 genome can lead to a scorable alteration in the phenotypes of this strain. Students outline and carry out a protocol for treatment of the yeast tester strain, utilizing the concept of dose/response and positive and negative controls. Students report on their results using a PowerPoint presentation to simulate giving a scientific presentation. The students' self-assessment of their knowledge indicated that, in all cases, the students felt that they knew more about the assay, mutagenesis, and the relationship between genotype and phenotype (P < 0.05) after completing the exercise.

  8. Feature combination networks for the interpretation of statistical machine learning models: application to Ames mutagenicity.

    PubMed

    Webb, Samuel J; Hanser, Thierry; Howlin, Brendan; Krause, Paul; Vessey, Jonathan D

    2014-03-25

    A new algorithm has been developed to enable the interpretation of black box models. The developed algorithm is agnostic to learning algorithm and open to all structural based descriptors such as fragments, keys and hashed fingerprints. The algorithm has provided meaningful interpretation of Ames mutagenicity predictions from both random forest and support vector machine models built on a variety of structural fingerprints.A fragmentation algorithm is utilised to investigate the model's behaviour on specific substructures present in the query. An output is formulated summarising causes of activation and deactivation. The algorithm is able to identify multiple causes of activation or deactivation in addition to identifying localised deactivations where the prediction for the query is active overall. No loss in performance is seen as there is no change in the prediction; the interpretation is produced directly on the model's behaviour for the specific query. Models have been built using multiple learning algorithms including support vector machine and random forest. The models were built on public Ames mutagenicity data and a variety of fingerprint descriptors were used. These models produced a good performance in both internal and external validation with accuracies around 82%. The models were used to evaluate the interpretation algorithm. Interpretation was revealed that links closely with understood mechanisms for Ames mutagenicity. This methodology allows for a greater utilisation of the predictions made by black box models and can expedite further study based on the output for a (quantitative) structure activity model. Additionally the algorithm could be utilised for chemical dataset investigation and knowledge extraction/human SAR development.

  9. Mutagenic atmospheres resulting from the photooxidation of aromatic hydrocarbon and NOx mixtures

    NASA Astrophysics Data System (ADS)

    Riedel, Theran P.; DeMarini, David M.; Zavala, Jose; Warren, Sarah H.; Corse, Eric W.; Offenberg, John H.; Kleindienst, Tadeusz E.; Lewandowski, Michael

    2018-04-01

    Although many volatile organic compounds (VOCs) are regulated to limit air pollution and the consequent health effects, the photooxidation products generally are not. Thus, we examined the mutagenicity in Salmonella TA100 of photochemical atmospheres generated in a steady-state atmospheric simulation chamber by irradiating mixtures of single aromatic VOCs, NOx, and ammonium sulfate seed aerosol in air. The 10 VOCs examined were benzene; toluene; ethylbenzene; o-, m-, and p-xylene; 1,2,4- and 1,3,5-trimethylbenzene; m-cresol; and naphthalene. Salmonella were exposed at the air-agar interface to the generated atmospheres for 1, 2, 4, 8, or 16 h. Dark-control exposures produced non-mutagenic atmospheres, illustrating that the gas-phase precursor VOCs were not mutagenic at the concentrations tested. Under irradiation, all but m-cresol and naphthalene produced mutagenic atmospheres, with potencies ranging from 2.0 (p-xylene) to 11.4 (ethylbenzene) revertants m3 mgC-1 h-1. The mutagenicity was due exclusively to direct-acting late-generation products of the photooxidation reactions. Gas-phase chemical analysis showed that a number of oxidized organic chemical species enhanced during the irradiated exposure experiments correlated (r ≥ 0.81) with the mutagenic potencies of the atmospheres. Molecular formulas assigned to these species indicated that they likely contained peroxy acid, aldehyde, alcohol, and other functionalities.

  10. Addition Polyimides from Non-Mutagenic Diamines

    NASA Technical Reports Server (NTRS)

    Delvigs, Peter; Klopotek, David L.; Hardy-Green, DeNise; Meador, Michael A. (Technical Monitor)

    2001-01-01

    Studies were conducted to find an acceptable non-mutagenic diamine to replace 4,4'-methylenedianiline (MDA), a suspect carcinogen, which is currently being used in PMR-15 polyimide applications. Several diamines containing fluorine and trifluoromethyl substituent groups were synthesized. The diamines were polymerized with the dimethyl ester of 3,3',4,4'-benzophenone tetracarboxylic acid (BTDE), using the monomethyl ester of nadic acid (NE) as an endcap. The effect of diamine structure on rheological properties, glass transition temperature, and thermo-oxidative stability was investigated. Unidirectional laminates were fabricated from selected resins, using carbon fiber as the reinforcement. The results indicate that some of the diamines containing trifluoromethyl groups are non-mutagenic, and have potential to replace MDA in PMR polyimides for long-term applications at temperatures up to 300 C.

  11. Antigenotoxic activity of lactic acid bacteria, prebiotics, and products of their fermentation against selected mutagens.

    PubMed

    Nowak, Adriana; Śliżewska, Katarzyna; Otlewska, Anna

    2015-12-01

    Dietary components such as lactic acid bacteria (LAB) and prebiotics can modulate the intestinal microbiota and are thought to be involved in the reduction of colorectal cancer risk. The presented study measured, using the comet assay, the antigenotoxic activity of both probiotic and non-probiotic LAB, as well as some prebiotics and the end-products of their fermentation, against fecal water (FW). The production of short chain fatty acids by the bacteria was quantified using HPLC. Seven out of the ten tested viable strains significantly decreased DNA damage induced by FW. The most effective of them were Lactobacillus mucosae 0988 and Bifidobacterium animalis ssp. lactis Bb-12, leading to a 76% and 80% decrease in genotoxicity, respectively. The end-products of fermentation of seven prebiotics by Lactobacillus casei DN 114-001 exhibited the strongest antigenotoxic activity against FW, with fermented inulin reducing genotoxicity by 75%. Among the tested bacteria, this strain produced the highest amounts of butyrate in the process of prebiotic fermentation, and especially from resistant dextrin (4.09 μM/mL). Fermented resistant dextrin improved DNA repair by 78% in cells pre-treated with 6.8 μM methylnitronitrosoguanidine (MNNG). Fermented inulin induced stronger DNA repair in cells pre-treated with mutagens (FW, 25 μM hydrogen peroxide, or MNNG) than non-fermented inulin, and the efficiency of DNA repair after 120 min of incubation decreased by 71%, 50% and 70%, respectively. The different degrees of genotoxicity inhibition observed for the various combinations of bacteria and prebiotics suggest that this effect may be attributable to carbohydrate type, SCFA yield, and the ratio of the end-products of prebiotic fermentation. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Mutagenicity and estrogenicity of raw water and drinking water in an industrialized city in the Yangtze River Delta.

    PubMed

    Xiao, Sanhua; Lv, Xuemin; Zeng, Yifan; Jin, Tao; Luo, Lan; Zhang, Binbin; Zhang, Gang; Wang, Yanhui; Feng, Lin; Zhu, Yuan; Tang, Fei

    2017-10-01

    Public concern was aroused by frequently reported water pollution incidents in Taihu Lake and the Yangtze River. The pollution also caught and sustained the attention of the scientific community. From 2010 to 2016, raw water and drinking water samples were continually collected at Waterworks A and B (Taihu Lake) and Waterworks C (Yangtze River). The non-volatile organic pollutants in the water samples were extracted by solid phase extraction. Ames tests and yeast estrogen screen (YES) assays were conducted to evaluate the respective mutagenic and estrogenic effects. Water samples from the Yangtze River-based Waterworks C possessed higher mutagenicity than those from Taihu Lake-based Waterworks A (P<0.001) and Waterworks B (P = 0.026). Water treatment enhanced the direct mutagenicity (P = 0.022), and weakened the estrogenicity of the raw water (P<0.001) with a median removal rate of 100%. In fact, very few of the finished samples showed estrogenic activity. Raw water samples from Waterworks A showed weaker estrogenicity than those from Waterworks B (P = 0.034) and Waterworks C (P = 0.006). In summary, mutagenic effects in drinking water and estrogenic effects in raw water merited sustained attention. The Yangtze River was more seriously polluted by mutagenic and estrogenic chemicals than Taihu Lake was. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. SYNTHESIS, IN VITRO METABOLISM, MUTAGENICITY, AND DNA-ADDUCTION OF NAPHTHO[1,2-E]PYRENE

    EPA Science Inventory

    SYNTHESIS, IN V1TRO METABOLISM, MUTAGENICITY , AND DNA-ADDUCnON OF NAPHTHO[l ,2-e ]PYRENE

    Literature data, although limited, underscore the contribution of C24HI4 polycyclic aromatic hydrocarbons to the biological activity of the extracts of complex environmental samples....

  14. Novel naïve Bayes classification models for predicting the chemical Ames mutagenicity.

    PubMed

    Zhang, Hui; Kang, Yan-Li; Zhu, Yuan-Yuan; Zhao, Kai-Xia; Liang, Jun-Yu; Ding, Lan; Zhang, Teng-Guo; Zhang, Ji

    2017-06-01

    Prediction of drug candidates for mutagenicity is a regulatory requirement since mutagenic compounds could pose a toxic risk to humans. The aim of this investigation was to develop a novel prediction model of mutagenicity by using a naïve Bayes classifier. The established model was validated by the internal 5-fold cross validation and external test sets. For comparison, the recursive partitioning classifier prediction model was also established and other various reported prediction models of mutagenicity were collected. Among these methods, the prediction performance of naïve Bayes classifier established here displayed very well and stable, which yielded average overall prediction accuracies for the internal 5-fold cross validation of the training set and external test set I set were 89.1±0.4% and 77.3±1.5%, respectively. The concordance of the external test set II with 446 marketed drugs was 90.9±0.3%. In addition, four simple molecular descriptors (e.g., Apol, No. of H donors, Num-Rings and Wiener) related to mutagenicity and five representative substructures of mutagens (e.g., aromatic nitro, hydroxyl amine, nitroso, aromatic amine and N-methyl-N-methylenemethanaminum) produced by ECFP_14 fingerprints were identified. We hope the established naïve Bayes prediction model can be applied to risk assessment processes; and the obtained important information of mutagenic chemicals can guide the design of chemical libraries for hit and lead optimization. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Mutagenicity of edible palm oil on the Ghanaian market before and after repeated heating.

    PubMed

    Asare, George A; Okyere, Genevieve O; Asante, Matilda; Brown, Charles A; Santa, Sheila; Asiedu, Bernice

    2013-12-01

    Red palm oil produced in Ghana largely by village folks has never been tested for its mutagenic potential. The study aimed at determining the mutagenicity of high-energy heated red palm oil (RRPO) and refined, bleached imported palm oil (PO) on the Ghanaian market. Samples of RRPO and PO were 1× and 5× heated for 10 min at 180 °C with a cooling period of 5 h in-between. Unheated, together with heated samples, were tested for mutagenicity using Salmonella typhimurium TA 98 and TA 100 tester stains. Unheated PO was negative for the Ames mutagenicity test with TA 98 strain. However, 1× and 5× heated PO were mutagenic (P = 0.05, each). Testing PO, using TA 100 strain was negative. RRPO was mutagenic with TA 98 strain for heated oils (P = 0.05, each). Assays with TA 100 strain showed highly significant mutations (P = 0.001, each) that increased with increasing heating frequency. PO 1× and 5× heated samples caused significant frameshift mutation in the S. typhimurium TA 98 strain. RRPO caused highly significant point and frameshift mutations in heated samples. Furthermore, unheated RRPO mutagenic potential has serious health implications. © 2013 Institute of Food Technologists®

  16. Photosynthetic and biochemical mechanisms of an EMS-mutagenized cowpea associated with its resistance to cowpea severe mosaic virus.

    PubMed

    Souza, Pedro F N; Silva, Fredy D A; Carvalho, Fabricio E L; Silveira, Joaquim A G; Vasconcelos, Ilka M; Oliveira, Jose T A

    2017-01-01

    The seed treatment of a CPSMV-susceptible cowpea genotype with the mutagenic agent EMS generated mutagenized resistant plantlets that respond to the virus challenge by activating biochemical and physiological defense mechanisms. Cowpea is an important crop that makes major nutritional contributions particularly to the diet of the poor population worldwide. However, its production is low, because cowpea is naturally exposed to several abiotic and biotic stresses, including viral agents. Cowpea severe mosaic virus (CPSMV) drastically affects cowpea grain production. This study was conducted to compare photosynthetic and biochemical parameters of a CPSMV-susceptible cowpea (CE-31 genotype) and its derived ethyl methanesulfonate-mutagenized resistant plantlets, both challenged with CPSMV, to shed light on the mechanisms of virus resistance. CPSMV inoculation was done in the fully expanded secondary leaves, 15 days after planting. At 7 days post-inoculation, in vivo photosynthetic parameters were measured and leaves collected for biochemical analysis. CPSMV-inoculated mutagenized-resistant cowpea plantlets (MCPI) maintained higher photosynthesis index, chlorophyll, and carotenoid contents in relation to the susceptible (CE-31) CPSMV-inoculated cowpea (CPI). Visually, the MCPI leaves did not exhibit any viral symptoms neither the presence of the virus as examined by RT-PCR. In addition, MCPI showed higher SOD, GPOX, chitinase, and phenylalanine ammonia lyase activities, H 2 O 2 , phenolic contents, and cell wall lignifications, but lower CAT and APX activities in comparison to CPI. All together, these photosynthetic and biochemical changes might have contributed for the CPSMS resistance of MCPI. Contrarily, CPI plantlets showed CPSMV accumulation, severe disease symptoms, reduction in the photosynthesis-related parameters, chlorophyll, carotenoid, phenolic compound, and H 2 O 2 contents, in addition to increased β-1,3-glucanase, and catalase activities that might have

  17. Influence of fuel properties, nitrogen oxides, and exhaust treatment by an oxidation catalytic converter on the mutagenicity of diesel engine emissions.

    PubMed

    Bünger, Jürgen; Krahl, Jürgen; Weigel, Andreas; Schröder, Olaf; Brüning, Thomas; Müller, Michael; Hallier, Ernst; Westphal, Götz

    2006-08-01

    Particle emissions of diesel engines (DEP) content polycyclic aromatic hydrocarbons (PAH) these compounds cause a strong mutagenicity of solvent extracts of DEP. We investigated the influence of fuel properties, nitrogen oxides (NO( x )), and an oxidation catalytic converter (OCC) on the mutagenic effects of DEP. The engine was fuelled with common diesel fuel (DF), low-sulphur diesel fuel (LSDF), rapeseed oil methyl ester (RME), and soybean oil methyl ester (SME) and run at five different load modes in two series with and without installation of an OCC in the exhaust pipe. Particles from the cooled and diluted exhaust were sampled onto glass fibre filters and extracted with dichloromethane in a soxhlet apparatus. The mutagenicity of the extracts was tested using the Salmonella typhimurium/mammalian microsome assay with tester strains TA98 and TA100. Without OCC the number of revertant colonies was lower in extracts of LSDF than in extracts of DF. The lowest numbers of revertant colonies were induced by the plant oil derived fuels. In three load modes, operation with the OCC led to a reduction of the mutagenicity. However, direct mutagenic effects under heavy duty conditions (load mode A) were significantly increased for RME (TA98, TA100) and SME (TA98). A consistent but not significant increase in direct mutagenicity was observed for DF and LSDF at load mode A, and for DF at idling (load mode E) when emissions were treated with the OCC. These results raise concern over the use of oxidation catalytic converters with diesel engines. We hypothesise that the OCC increases formation of direct acting mutagens under certain conditions by the reaction of NO( x ) with PAH resulting in the formation of nitrated-PAH. Most of these compounds are powerful direct acting mutagens.

  18. Mutagenic synergism detected between dimethyl sulfate and X-rays but not found between N-methyl-N-nitrosourea and X-rays in the stamen hairs of Tradescantia clone BNL 4430.

    PubMed

    Shima, N; Ichikawa, S

    1995-09-01

    Mutagenic interactions with X-rays of two monofunctional alkylating agents, dimethyl sulfate (DMS) and N-methyl-N-nitrosourea (MNU), were studied in the stamen hairs of Tradescantia clone BNL 4430, a blue/pink heterozygote. The young inflorescence-bearing shoots with roots cultivated in the nutrient solution circulating growth chamber were used as tester plants. Synergism between two different mutagens was judged to have occurred when the mutation frequency observed after applying the two mutagens concurrently was statistically significantly higher than the mutation frequency expected from the additive effects of the two mutagens. Clear synergistic effects in inducing somatic pink mutations were detected with all combinations of doses of DMS and X-rays examined, even in a relatively low X-ray dose range (down to 299 mGy), resembling those confirmed earlier between ethyl methanesulfonate (EMS) and X-rays, but somewhat differing from the synergisms observed earlier between methyl methanesulfonate (MMS) and X-rays. On the other hand, no mutagenic synergism was detected between MNU and X-rays, even in a relatively high X-ray dose range (up to 862 mGy). The presence or absence of mutagenic synergisms of these alkylating agents with X-rays could be related to the action mechanism of each alkylating agent.

  19. Automatic knowledge extraction from chemical structures: the case of mutagenicity prediction.

    PubMed

    Ferrari, T; Cattaneo, D; Gini, G; Golbamaki Bakhtyari, N; Manganaro, A; Benfenati, E

    2013-01-01

    This work proposes a new structure-activity relationship (SAR) approach to mine molecular fragments that act as structural alerts for biological activity. The entire process is designed to fit with human reasoning, not only to make the predictions more reliable but also to permit clear control by the user in order to meet customized requirements. This approach has been tested on the mutagenicity endpoint, showing marked prediction skills and, more interestingly, bringing to the surface much of the knowledge already collected in the literature as well as new evidence.

  20. Mutagenicity of diesel engine exhaust is eliminated in the gas phase by an oxidation catalyst but only slightly reduced in the particle phase.

    PubMed

    Westphal, Götz A; Krahl, Jürgen; Munack, Axel; Ruschel, Yvonne; Schröder, Olaf; Hallier, Ernst; Brüning, Thomas; Bünger, Jürgen

    2012-06-05

    mutagenic effects most effectively in the gas phase. Mutagenicity of particle extracts was less efficiently diminished. No significant differences of mutagenic effects were observed among the tested fuels. In conclusion, the benefits of the DOC concern regulated emissions except NO(X) as well as nonregulated emissions such as the mutagenicity of the exhaust. The reduction of mutagenicity was particularly observed in the condensates of the gas phase. This is probably due to better accessibility of gaseous mutagenic compounds during the passage of the DOC in contrast to the particle-bound mutagens. Concerning the particulate emissions DOC especially decreased ultrafine particles.

  1. Polar extracts from (Tunisian) Acacia salicina Lindl. Study of the antimicrobial and antigenotoxic activities

    PubMed Central

    2012-01-01

    Background Methanolic, aqueous and Total Oligomer Flavonoids (TOF)-enriched extracts obtained from the leaves of Acacia salicina 'Lindl.' were investigated for antibacterial, antimutagenic and antioxidant activities. Methods The antimicrobial activity was tested on the Gram positive and Gram negative reference bacterial strains. The Mutagenic and antimutagenic activities against direct acting mutagens, methylmethane sulfonate (MMS) and 4-nitro-o-phenylenediamine (NOPD), and indirect acting mutagens, 2-aminoanthracene (2-AA) and benzo[a]pyrene (B(a)P) were performed with S. typhimurium TA102 and TA98 assay systems. In addition, the enzymatic and nonenzymatic methods were employed to evaluate the anti-oxidative effects of the tested extracts. Results A significant effect against the Gram positive and Gram negative reference bacterial strains was observed with all the extracts. The mutagenic and antimutagenic studies revealed that all the extracts decreased the mutagenicity induced by B(a)P (7.5 μg/plate), 2-AA (5 μg/plate), MMS (1.3 mg/plate) and NOPD (10 μg/plate). Likewise, all the extracts showed an important free radical scavenging activity towards the superoxide anion generated by the xanthine/xanthine oxidase assay system, as well as high Trolox Equivalent Antioxidant Capacity (TEAC), against the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS)+• radical. TOF-enriched extract exhibited the highest protective effect against free radicals, direct acting-mutagen and metabolically activated S9-dependent mutagens. Conclusions The present study indicates that the extracts from A. salicina leaves are a significant source of compounds with the antimutagenic and antioxidant activities, and this may be useful for developing potential chemopreventive substances. PMID:22490278

  2. Bioavailability and biotransformation of the mutagenic component of particulate emissions present in motor exhaust samples.

    PubMed Central

    Vostal, J J

    1983-01-01

    The pharmacokinetic concepts of bioavailability and biotransformation are introduced into the assessment of public health risk from experimental data concerning the emissions of potentially mutagenic and carcinogenic substances from motor vehicles. The inappropriateness of an automatic application in the risk assessment process of analytical or experimental results, obtained with extracts and procedures incompatible with the biological environment, is illustrated on the discrepancy between short-term laboratory tests predictions that wider use of diesel engines on our roads will increase the risk of respiratory cancer and the widely negative epidemiological evidence. Mutagenic activity of diesel particulates was minimal or negative when tested in extracts obtained with biological fluids, was substantially dependent on the presence of nitroreductase in the microbial tester strain, and disappeared completely 48 hr after the diesel particles had been phagocytized by alveolar macrophages. Similarly, long-term animal inhalation exposures to high concentrations of diesel particles did not induce the activity of hydrocarbon metabolizing enzymes or specific adverse immune response unless organic solvent extracts of diesel particles were administered intratracheally or parenterally in doses that highly exceed the predicted levels of public exposure even by the year 2000. Furthermore, the suspected cancer producing effects of inhaled diesel particles have thus far not been verified by experimental animal models or available long-term epidemiological observations. It is concluded that unless the biological accessibility of the active component on the pollutant as well as its biotransformation and clearance by natural defense mechanisms are considered, lung cancer risk assessment based solely on laboratory microbial tests will remain an arbitrary and unrealistic process and will not provide meaningful information on the potential health hazard of a pollutant. PMID:6186478

  3. TOXICITY REDUCTION EVALUATION (TRE) AT A MUNICIPAL WASTEWATER TREATMENT PLANT USING MUTAGENICITY AS AN END- POINT

    EPA Science Inventory

    Previous work revealed substantial levels of mutagenicity in effluents from certain municipal wastewater treatment plants. One of these treatment plants was selected for further study to track the effluent mutagenicity to its sources, to chemically characterize the mutagenicity, ...

  4. Loss of heterocyclic amine mutagens by insoluble hemicellulose fiber and high-molecular-weight soluble polyphenolics of coffee.

    PubMed

    Kato, T; Takahashi, S; Kikugawa, K

    1991-01-01

    The presence of 2 kinds of components in brewed and instant coffee that could remove and destroy heterocyclic amine mutagens was demonstrated. The component that could remove the mutagens was insoluble fiber composed of hemicellulose. The fiber could tightly adsorb the mutagens Trp-P-1, Trp-P-2, Glu-P-1 and A alpha C, and those generated in roasted coffee beans. The component that could destroy the mutagens was high-molecular-weight soluble polyphenolics. They might be converted into quinone derivatives in the presence of molecular oxygen. The quinone derivatives might destroy the mutagens. The fibers and the polyphenolics in one cup of brewed or instant coffee had the capacity to remove and destroy a substantial amount of the mutagens in pyrolysates of foodstuffs.

  5. Safety and mutagenicity evaluation of red mold dioscorea fermented from Monascus purpureus NTU 568.

    PubMed

    Hsu, Li-Chuan; Hsu, Ya-Wen; Hong, Chih-Chun; Pan, Tzu-Ming

    2014-05-01

    Monascus-fermented products, including red mold rice and red mold dioscorea, have been developed as functional foods with many health benefits. We performed safety and mutagenic evaluations on red mold dioscorea powder (RMDP) fermented from Monascus purpureus NTU 568. The results of Ames test using Salmonella typhimurium strains TA97a, TA98, TA100, TA102, and TA1535 showed that RMDP (⩽5 mg/plate) was not mutagenic. The mammalian chromosomal aberration test showed that the number of Chinese hamster ovary cells with abnormal chromosomes was <3% after RMDP treatment (maximum concentration: 5 mg/mL). Imprinting control region mice were used to estimate the genotoxicity of RMDP. Compared with the control, high-dose RMDP administration (2000 mg/kg) did not show significant differences in the number of reticulocytes or the occurrence of micronucleated reticulocytes. A 28-day oral toxicity assay in Sprague-Dawley rats was performed to investigate the no observed adverse effect level of RMDP. Compared with the control, high-dose RMDP administration (2000 mg/kg) caused no toxicological responses such as mortality, variation in body weight, or toxicopathologic lesions. Thus, RMDP from M. purpureus NTU 568 shows no significant mutagenic or toxic effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. THE MUTAGENIC EFFECT OF VANILLIN AND OF SOME OF ITS DERIVATIVES (in Russian)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Efremova, G.I.

    1962-09-11

    A dose of 3 to 60 Mgs of crystalline vanillin was added to nutrient broth for Drosophila melanogaster in the early larval stage (48 hours old) or as grown males. The progeny of the flies was analyzed for the number of lethal mutations associated with sex. An increase in mutagenesis by a factor of four was observed. The 5-iodovanillin and 5-bromovanillin derivates had an even higher mutagenic effect than vanillin, particularly on the full-grown sex cells (spermatogonia). The mutagenic effect of vanillin was increased by dissolving it in a 2M solution of triacetin readily soluble. The incidence of melanitic cancermore » was increased significantly by adding vanillin to the diet of an insect. The results are of significance because of the widespread use of vanillin in the food industry. Vanillin acts as an antioxidant, and interacts with various oxidases. (TTT)« less

  7. Two dechlorinated chlordecone derivatives formed by in situ chemical reduction are devoid of genotoxicity and mutagenicity and have lower proangiogenic properties compared to the parent compound.

    PubMed

    Legeay, Samuel; Billat, Pierre-André; Clere, Nicolas; Nesslany, Fabrice; Bristeau, Sébastien; Faure, Sébastien; Mouvet, Christophe

    2018-05-01

    Chlordecone (CLD) is a chlorinated hydrocarbon insecticide, now classified as a persistent organic pollutant. Several studies have previously reported that chronic exposure to CLD leads to hepatotoxicity, neurotoxicity, raises early child development and pregnancy complications, and increases the risk of liver and prostate cancer. In situ chemical reduction (ISCR) has been identified as a possible way for the remediation of soils contaminated by CLD. In the present study, the objectives were (i) to evaluate the genotoxicity and the mutagenicity of two CLD metabolites formed by ISCR, CLD-5a-hydro, or CLD-5-hydro (5a- or 5- according to CAS nomenclature; CLD-1Cl) and tri-hydroCLD (CLD-3Cl), and (ii) to explore the angiogenic properties of these molecules. Mutagenicity and genotoxicity were investigated using the Ames's technique on Salmonella typhimurium and the in vitro micronucleus micromethod with TK6 human lymphoblastoid cells. The proangiogenic properties were evaluated on the in vitro capillary network formation of human primary endothelial cells. Like CLD, the dechlorinated derivatives of CLD studied were devoid of genotoxic and mutagenic activity. In the assay targeting angiogenic properties, significantly lower microvessel lengths formed by endothelial cells were observed for the CLD-3Cl-treated cells compared to the CLD-treated cells for two of the three tested concentrations. These results suggest that dechlorinated CLD derivatives are devoid of mutagenicity and genotoxicity and have lower proangiogenic properties than CLD.

  8. Mutagenicity and Nitropyrene Concentration of Indoor Air Particulates Exhausted from a Kerosene Heater*1

    PubMed Central

    Kinouchi, Takemi; Nishifuji, Keiko; Tsutsui, Hideshi; Hoare, Sadako Louise

    1988-01-01

    The particulates in a room warmed with a radiant kerosene heater were collected, extracted and fractionated into diethyl ether‐soluble neutral, acidic and basic fractions. The mutagenicity of these fractions was measured with Salmonella typhimurium strains TA98, TA98NR, TA98/1,8‐DNP6 and TA100 in the presence and ahsence of S9 mix. Room air without the heater showed very low mutagenicity. However, a sample from a room at the beginning of the burning period showed very high mutagenicity (237 His+ revertants/plate/m*3 of air in strain TA98 in the absence of S9 mix). In contrast, emissions from the heater after it was burning stably showed low mutagenicity (9 His+ revertants/plate/m*3). The crude extract of particulates from the heater at the beginning of the burning period was analyzed by high‐pressure liquid chromatography (HPLC) and showed a considerable amount of nitropyrenes (NPs); the concentrations of 1‐NP and 1,6‐diNP were 1.62 ng and 0.149 ng/m*3 of air, respectively, and accounted for 1.2% and 17.6%, respectively, of the mutagenicity in strain TA98 in the absence of S9 mix. In addition, an HPLC‐Ames histogram showed that peaks of mutagenicity corresponding to 1‐NP and diNPs accounted for 75.7% (1‐NP, 4.9%; 1,6‐diNP, 17.1%; 1,8‐diNP, 46.3%; 1,3‐diNP, 7.4%) of the HPLC‐recovered mutagenicity for strain TA98 without S9 mix. These results suggest that kerosene heaters, especially immediately after ignition, create mutagenic substances such as NPs. PMID:3128503

  9. URINARY MUTAGENICITY AND COLORECTAL ADENOMA RISK

    EPA Science Inventory

    Abstract

    We investigated urinary mutagenicity and colorectal adenoma risk in a clinic-based, case-control study of currently nonsmoking cases (n = 143) and controls (n = 156). Urinary organics were extracted by C18/methanol from 12-h overnight urine samples, and mutagenici...

  10. Mutagenic activity of heavy metals in soils of wayside slopes

    NASA Astrophysics Data System (ADS)

    Fedorova, A. I.; Kalaev, V. N.; Prosvirina, Yu. G.; Goryainova, S. A.

    2007-08-01

    The genotoxic properties of soils polluted with heavy metals were studied on two wayside slopes covered with trees in the city of Voronezh. The nucleolar test in cells of the apical meristem of Zebrina pendula Schnizl. roots was used. The genotoxic effect of the soils was revealed according to the increased number of 2-and 3-nucleolar cells (from 41 to 54% and from 19 to 23% in the upper part of the first and second slopes, respectively; in the control, their number was 18 and 7%). The mean number of nucleoli per cell increased from 1.7 to 1.95 in the experiment and 1.31 in the control. The increased vehicle emissions, especially when cars go up the slopes (mainly in the upper and middle parts), correlated with the elevated heavy metal (Pb, Cu, Cd, and Zn) contents in the soil. The mutagenic substances may be removed to the Voronezh Reservoir, where they may be accumulated in some living organisms.

  11. The mutagenic assessment of an electronic-cigarette and reference cigarette smoke using the Ames assay in strains TA98 and TA100.

    PubMed

    Thorne, D; Crooks, I; Hollings, M; Seymour, A; Meredith, C; Gaca, M

    2016-12-01

    Salmonella typhimurium strains TA98 and TA100 were used to assess the mutagenic potential of the aerosol from a commercially available, rechargeable, closed system electronic-cigarette. Results obtained were compared to those for the mainstream smoke from a Kentucky reference (3R4F) cigarette. Two different test matrices were assessed. Aerosol generated from the e-cigarette was trapped on a Cambridge filter pad, eluted in DMSO and compared to cigarette smoke total particulate matter (TPM), which was generated in the same manner for mutagenicity assessment in the Salmonella assay. Fresh e-cigarette and cigarette smoke aerosols were generated on the Vitrocell ® VC 10 smoking robot and compared using a modified scaled-down 35mm air agar interface (AAI) methodology. E-cigarette aerosol collected matter (ACM) was found to be non-mutagenic in the 85mm plate incorporation Ames assay in strains TA98 and TA100 conducted in accordance with OECD 471, when tested up to 2400μg/plate. Freshly generated e-cigarette aerosol was also found to be negative in both strains after an AAI aerosol exposure, when tested up to a 1L/min dilution for up to 3h. Positive control responses were observed in both strains, using benzo[a]pyrene, 2-nitrofluorene, sodium azide and 2-aminoanthracene in TA98 and TA100 in the presence and absence of metabolic activation respectively. In contrast, cigarette smoke TPM and aerosol from 3R4F reference cigarettes were found to be mutagenic in both tester strains, under comparable test conditions to that of e-cigarette exposure. Limited information exists on the mutagenic activity of captured e-cigarette particulates and whole aerosol AAI approaches. With the lower toxicant burden of e-cigarette aerosols compared to cigarette smoke, it is clear that a more comprehensive Ames package of data should be generated when assessing e-cigarettes, consisting of the standard OECD-five, TA98, TA100, TA1535, TA1537 (or TA97) and E. coli (or TA102). In addition, TA104

  12. The efficiency of solvent extraction of mutagenic compounds in particulates exhausted from a small diesel engine.

    PubMed

    Tahara, I; Kinouchi, T; Kataoka, K; Ohnishi, Y

    1994-06-01

    Organic materials were extracted from particulates exhausted from a small diesel engine (displacement 269 ml) by the ultrasonic extraction method with three different solvent systems, methanol, dichloromethane and a 4:1 (v:v) mixture of benzene and ethanol. These solvent-extracted materials were tested for mutagenic activity by the Ames Salmonella/microsome assay system using Salmonella typhimurium strains TA98, TA100, TA98NR and TA98/1,8-DNP6. The concentrations of 1-nitropyrene (1-NP) and 1,6-dinitropyrene (1,6-diNP) in these extracted materials were also measured after nitroreduction by high pressure liquid chromatography. The methanol-extracted and benzene-ethanol-extracted materials showed the lowest and the highest mutagenic activity, respectively. The methanol-extracted, dichloromethane-extracted and benzene-ethanol-extracted materials induced 260, 1,570 and 3,240 His+ revertants per plate per mg of extracted materials, respectively, from strain TA98 in the absence of S9 mix. These materials showed decreased mutagenicity for strains TA98NR and TA98/1,8-DNP6, indicating that the particulates in the diesel engine exhaust contained 1-NP and diNPs. Actually, the amount of 1-NP and 1,6-diNP in the methanol-extracted, dichloromethane-extracted and benzene-ethanol-extracted materials were 17.0 and 0.03 ng, 37.5 and 0.97 ng, and 71.3 and 1.03 ng per mg of extracted materials, respectively, accounting for 11.9 and 3.2%, 4.4 and 17.3%, and 4.0 and 8.9%, respectively, of the total mutagenicity of the extracted materials. From these results it is concluded that a mixture of benzene-ethanol (4:1, v/v) is the most suitable solvent for extraction of organic matter containing nitrated polycyclic aromatic hydrocarbons such as NPs from particulates in diesel engine exhaust.

  13. Cellular Mutagenicity and Heavy Metal Concentrations of Leachates Extracted from the Fly and Bottom Ash Derived from Municipal Solid Waste Incineration

    PubMed Central

    Chen, Po-Wen; Liu, Zhen-Shu; Wun, Min-Jie; Kuo, Tai-Chen

    2016-01-01

    Two incinerators in Taiwan have recently attempted to reuse the fly and bottom ash that they produce, but the mutagenicity of these types of ash has not yet been assessed. Therefore, we evaluated the mutagenicity of the ash with the Ames mutagenicity assay using the TA98, TA100, and TA1535 bacterial strains. We obtained three leachates from three leachants of varying pH values using the toxicity characteristic leaching procedure test recommended by the Taiwan Environmental Protection Agency (Taiwan EPA). We then performed the Ames assay on the harvested leachates. To evaluate the possible relationship between the presence of heavy metals and mutagenicity, the concentrations of five heavy metals (Cd, Cr, Cu, Pb, and Zn) in the leachates were also determined. The concentrations of Cd and Cr in the most acidic leachate from the precipitator fly ash and the Cd concentration in the most acidic leachate from the boiler fly ash exceeded the recommended limits. Notably, none of the nine leachates extracted from the boiler, precipitator, or bottom ashes displayed mutagenic activity. This data partially affirms the safety of the fly and bottom ash produced by certain incinerators. Therefore, the biotoxicity of leachates from recycled ash should be routinely monitored before reusing the ash. PMID:27827867

  14. HAZARD IDENTIFICATION: EFFICIENCY OF SHORT-TERM TESTS IN IDENTIFYING GERM CELL MUTAGENS AND PUTATIVE NONGENOTOXIC CARCINOGENS

    EPA Science Inventory

    For more than a decade, mutagenicity tests have had a clearly defined role in the identification of potential human mutagens and an ancillary role in the identification of potential human carcinogens. he efficiency of short-term tests in identifying germ cell mutagens has been ex...

  15. ASSOCIATION BETWEEN URINARY MUTAGENICITY AND RISK OF COLORECTAL ADENOMAS IN A CLINIC-BASED CASE-CONTROL STUDY

    EPA Science Inventory

    ASSOCIATION BETWEEN URINARY MUTAGENICITY AND RISK OF COLORECTAL ADENOMAS IN A CLINIC-BASED CASE-CONTROL STUDY

    Humans are exposed to a variety of mutagens from diet, smoking, or occupation. To explore if exposure to mutagens was related to the risk of colorectal adenomas i...

  16. Combusting vegetable oils in diesel engines: the impact of unsaturated fatty acids on particle emissions and mutagenic effects of the exhaust.

    PubMed

    Bünger, Jürgen; Bünger, Jörn F; Krahl, Jürgen; Munack, Axel; Schröder, Olaf; Brüning, Thomas; Hallier, Ernst; Westphal, Götz A

    2016-06-01

    High particle emissions and strong mutagenic effects were observed after combustion of vegetable oil in diesel engines. This study tested the hypothesis that these results are affected by the amount of unsaturated or polyunsaturated fatty acids of vegetable oils. Four different vegetable oils (coconut oil, CO; linseed oil, LO; palm tree oil, PO; and rapeseed oil, RO) and common diesel fuel (DF) were combusted in a heavy-duty diesel engine. The exhausts were investigated for particle emissions and mutagenic effects in direct comparison with emissions of DF. The engine was operated using the European Stationary Cycle. Particle masses were measured gravimetrically while mutagenicity was determined using the bacterial reverse mutation assay with tester strains TA98 and TA100. Combustion of LO caused the largest amount of total particulate matter (TPM). In comparison with DF, it particularly raised the soluble organic fraction (SOF). RO presented second highest TPM and SOF, followed by CO and PO, which were scarcely above DF. RO revealed the highest number of mutations of the vegetable oils closely followed by LO. PO was less mutagenic, but still induced stronger effects than DF. While TPM and SOF were strongly correlated with the content of polyunsaturated fatty acids in the vegetable oils, mutagenicity had a significant correlation with the amount of total unsaturated fatty acids. This study supports the hypothesis that numbers of double bounds in unsaturated fatty acids of vegetable oils combusted in diesel engines influence the amount of emitted particles and the mutagenicity of the exhaust. Further investigations have to elucidate the causal relationship.

  17. MUTAGENIC CHARACTERISTICS OF RIVER WATERS FLOWING THROUGH LARGE METROPOLITAN AREAS IN NORTH AMERICA

    EPA Science Inventory

    Mutagenic characteristics of river waters flowing through large metropolitan areas in North America

    The hanging technique using blue rayon, which specifically adsorbs mutagens with multicyclic planar structures, has the advantages over most conventional methods of not havi...

  18. Extinction of Zika virus and Usutu virus by lethal mutagenesis reveals different patterns of sensitivity to three mutagenic drugs.

    PubMed

    Bassi, Maria Rosaria; Sempere, Raquel Navarro; Meyn, Prashansa; Polacek, Charlotta; Arias, Armando

    2018-06-18

    Flaviviruses constitute an increasing source of public health concern with growing numbers of pathogens causing disease, and a geographic spread to temperate climates. Despite a large body of evidence supporting mutagenesis as a conceivable antiviral strategy, there is currently no data on the sensitivity to increased mutagenesis for Zika virus (ZIKV) and Usutu virus (USUV), two emerging flaviviral threats. In this study, we demonstrate that both viruses are sensitive to three ribonucleosides that have shown mutagenic activity against other RNA viruses - favipiravir, ribavirin and 5-fluorouracil - while they remain unaffected by a mutagenic deoxyribonucleoside. Serial cell culture passages of ZIKV in the presence of these compounds resulted in the rapid extinction of infectivity, suggesting elevated sensitivity to mutagenesis. USUV extinction was achieved when a 10-fold dilution was applied between every passage, but not in experiments involving undiluted virus, indicating an overall lower susceptibility than ZIKV. Although both viruses are inhibited by the same three drugs, ZIKV is relatively more susceptive to serial passage in the presence of purine analogues (favipiravir and ribavirin) while USUV replication is suppressed more efficiently by 5-fluorouracil. These differences in sensitivity typically correlate with the increases in the mutation frequencies observed in each nucleoside treatment. These results are relevant to the development of efficient therapies based on lethal mutagenesis, and support the rational selection of different mutagenic nucleosides for each pathogen. We will discuss the implications of these results to the fidelity of flavivirus replication, and the design of antiviral therapies based on lethal mutagenesis. Copyright © 2018 Bassi et al.

  19. Mutagenicity and cytoxicity of irradiated foods and food components*

    PubMed Central

    Schubert, Jack

    1969-01-01

    The preservation of foods by treatment with ionizing radiation can significantly increase the world's food resources by reducing spoilage and waste. However, irradiation can bring about chemical transformations in food and food components resulting in the formation of potential mutagens, particularly hydrogen peroxide and various organic peroxides. In order to evaluate the safety of irradiated foods for general consumption by the public, and, indeed, the safety of all foods subjected to environmental factors such as food additives, pesticides, drugs, air and water pollutants, etc., it is necessary to supplement the usual feeding tests with procedures designed to detect all classes of genetic damage. This article includes a comprehensive critical review of (1) the experimental evidence relating to the presence of mutagenic and cytotoxic agents in irradiated media, as detected by their effects on mammalian and non-mammalian cells; (2) the chemical changes produced in irradiated media, especially those which produce known mutagenic substances; and (3) new and convenient in vivo methods for the detection and evaluation of genetic damage in mammals. PMID:4908553

  20. Evaluation of the mutagenicity and antimutagenicity of Ziziphus joazeiro Mart. bark in the micronucleus assay

    PubMed Central

    Boriollo, Marcelo Fabiano Gomes; Resende, Marielly Reis; da Silva, Thaísla Andrielle; Públio, Juliana Yoshida; Souza, Luiz Silva; Dias, Carlos Tadeu dos Santos; de Mello Silva Oliveira, Nelma; Fiorini, João Evangelista

    2014-01-01

    The aim of this study was to evaluate the mutagenicity (clastogenicity/aneugenicity) of a glycolic extract of Ziziphus joazeiro bark (GEZJ) by the micronucleus assay in mice bone marrow. Antimutagenic activity was also assessed using treatments associated with GEZJ and doxorubicin (DXR). Mice were evaluated 24–48 h after exposure to positive (N-nitroso-N-ethylurea, NEU - 50 mg.kg−1 and DXR - 5 mg.kg−1) and negative (150 mM NaCl) controls, as well as treatment with GEZJ (0.5–2 g.kg−1), GEZJ (2 g.kg−1) + NEU and GEZJ (2 g.kg−1) + DXR. There were no significant differences in the frequencies of micronucleated polychromatic erythrocytes in mice treated with GEJZ and GEJZ + DXR compared to the negative controls, indicating that GEZJ was not mutagenic. Analysis of the polychromatic:normochromatic erythrocyte ratio revealed significant differences in the responses to doses of 0.5 g.kg−1 and 1–2 g.kg−1 and the positive control (NEU). These results indicated no systemic toxicity and moderate toxicity at lower and higher doses of GEZJ. The lack of mutagenicity and systemic toxicity in the antimutagenic assays, especially for treatment with GEZJ + DXR, suggested that phytochemical compounds in Z. joazeiro bark attenuated DXR-induced mutagenicity and the moderate systemic toxicity of a high dose of Z. joazeiro bark (2 g.kg−1). Further studies on the genotoxicity of Z. joazeiro extracts are necessary to establish the possible health risk in humans and to determine the potential as a chemopreventive agent for therapeutic use. PMID:25071409

  1. Mutagenicity of p-aminophenol in E. coli WP2uvrA/pKM101 and its relevance to oxidative DNA damage.

    PubMed

    Yoshida, R; Oikawa, S; Ogawa, Y; Miyakoshi, Y; Ooida, M; Asanuma, K; Shimizu, H

    1998-07-08

    It was recently reported that p-aminophenol (p-AP) induces DNA cleavage in mouse lymphoma cells, CHO cells and human lymphoblastoid cells. The mutagenicity of p-AP has not, however, been detected by reverse mutation assays. The purpose of this study was to assess the mutagenicity of p-AP by reverse mutation assay using Escherichia coli WP2uvrA/pKM101, which has a spectrum for detecting mutations different from those of other strains in the family with an AT base pair at the mutation site and has higher sensitivity to certain oxidative mutagens as compared to other strains. We found that p-AP was mutagenic to E. coli WP2uvrA/pKM101. The mutagenic activity of this compound was suppressed with the addition of dimethylsulfoxide or catalase, suggesting the involvement of active oxygen species in the mutagenic process induced by p-AP. To further elucidate the underlying mechanism, we used isolated DNA for the following experiments. It was revealed, by gel electrophoretic analysis, that p-AP induced DNA cleavage in the presence of Fe(III). However, p-AP alone did not induce this cleavage. Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by p-AP in calf thymus DNA was also detected in the presence of Fe(III) by HPLC with an electrochemical detector. ESR-spin trapping experiments using DMPO detected the production of hydroxyl radical (.OH) in the solution of p-AP with Fe(III). Both p-AP mediated DNA damages and .OH production by p-AP in the presence of Fe(III) were completely inhibited by .OH scavengers (ethanol, mannitol, sodium formate, dimethylsulfoxide) and catalase. These results suggest that .OH derived from the reaction between H2O2 and Fe(III) (Fenton reaction) participates in the oxidative DNA damage. Accordingly, the same mechanism might be working in E. coli WP2uvrA/pKM101 during induction of the mutation by p-AP.

  2. ASSESSMENT OF STANDARD REFERENCE COMPOUNDS FOR COMPARATIVE STUDIES USING THE SALMONELLA TYPHIMURIUM MUTAGENICITY ASSAY: I. WITHOUT EXOGENOUS ACTIVATION

    EPA Science Inventory

    Finney (1978) described a bioassay as an experiment for estimating the nature, constitution, or potency of a material by means of the eaction that follows its application to living matter. n this paper, two independent laboratories tested 10 known Salmonella mutagens in order to ...

  3. Protective Effect of Prolactin against Methylmercury-Induced Mutagenicity and Cytotoxicity on Human Lymphocytes

    PubMed Central

    Silva-Pereira, Liz Carmem; da Rocha, Carlos Alberto Machado; Cunha, Luiz Raimundo Campos da Silva e; da Costa, Edmar Tavares; Guimarães, Ana Paula Araújo; Pontes, Thais Brilhante; Diniz, Domingos Luiz Wanderley Picanço; Leal, Mariana Ferreira; Moreira-Nunes, Caroline Aquino; Burbano, Rommel Rodríguez

    2014-01-01

    Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg) is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL) may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage) treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg. PMID:25247425

  4. Mutagenic Azo Dyes, Rather Than Flame Retardants, Are the Predominant Brominated Compounds in House Dust.

    PubMed

    Peng, Hui; Saunders, David M V; Sun, Jianxian; Jones, Paul D; Wong, Chris K C; Liu, Hongling; Giesy, John P

    2016-12-06

    Characterization of toxicological profiles by use of traditional targeted strategies might underestimate the risk of environmental mixtures. Unbiased identification of prioritized compounds provides a promising strategy for meeting regulatory needs. In this study, untargeted screening of brominated compounds in house dust was conducted using a data-independent precursor isolation and characteristic fragment (DIPIC-Frag) approach, which used data-independent acquisition (DIA) and a chemometric strategy to detect peaks and align precursor ions. A total of 1008 brominated compound peaks were identified in 23 house dust samples. Precursor ions and formulas were identified for 738 (73%) of the brominated compounds. A correlation matrix was used to cluster brominated compounds; three large groups were found for the 140 high-abundance brominated compounds, and only 24 (17%) of these compounds were previously known flame retardants. The predominant class of unknown brominated compounds was predicted to consist of nitrogen-containing compounds. Following further validation by authentic standards, these compounds (56%) were determined to be novel brominated azo dyes. The mutagenicity of one major component was investigated, and mutagenicity was observed at environmentally relevant concentrations. Results of this study demonstrated the existence of numerous unknown brominated compounds in house dust, with mutagenic azo dyes unexpectedly being identified as the predominant compounds.

  5. In vivo formation of mutagens by intraperitoneal administration of polycyclic aromatic hydrocarbons in animals during exposure to nitrogen dioxide.

    PubMed

    Miyanishi, K; Kinouchi, T; Kataoka, K; Kanoh, T; Ohnishi, Y

    1996-07-01

    Consumption of fossil fuels has increased indoor and outdoor concentrations of polycyclic aromatic hydrocarbons (PAHs) and nitrogen dioxide (NO2). To study the combined effect of PAH administration and NO2 exposure on mutagenicity of urine from animals we injected 400 mg/kg body wt i.p. one of five kinds of PAH (pyrene, fluoranthene, fluorene, anthracene and chrysene) into ICR mice, Wistar rats, Syrian golden hamsters or Hartley guinea pigs after exposure to 20 p.p.m. NO2 gas for 24 h and then exposed the animals to NO2 gas for an additional 24 h. During the latter 24 h we collected the urine and assayed its mutagenicity with the Ames Salmonella strains after treatment with beta-glucuronidase and arylsulfatase and extraction with dichloromethane. The urine from mice treated with both PAH and NO2 showed high mutagenicity for Salmonella typhimurium strains TA98 and TA100, whereas the urine from mice treated with PAH and air showed almost no mutagenic activity. The mutagenicity was decreased in nitroreductase- and acetyltransferase-deficient strains TA98NR and TA98/1,8-DNP6 respectively. Treatment with a mixture of 20% of each of the five kinds of PAH and NO2 augmented the urinary mutagenicity of mice 1.5-fold. The urine from hamsters treated with pyrene or fluoranthene and NO2 was also highly mutagenic, but that from rats or guinea pigs was not very mutagenic. The mutagenicity was also decreased in strains TA98NR and TA98/1,8-DNP6. These results suggest that the urine contains nitro compounds and that the nitration of PAHs occurs in the body of animals under exposure to NO2 gas. Actually, the nitrated metabolites of pyrene, 1-nitro-6/8-hydroxypyrene and 1-nitro-3-hydroxypyrene, were detected in the urine from mice treated with pyrene under exposure to NO2 gas. To elucidate the mechanism of in vivo nitration, NO2 (20 p.p.m.) was bubbled through 50 mM Tris-HCl buffer (pH 7.4) or dichloromethane solution containing pyrene or 1-hydroxypyrene (10 microg/ml). Pyrene was

  6. Dietary Intake of Meat Cooking-Related Mutagens (HCAs) and Risk of Colorectal Adenoma and Cancer: A Systematic Review and Meta-Analysis.

    PubMed

    Chiavarini, Manuela; Bertarelli, Gaia; Minelli, Liliana; Fabiani, Roberto

    2017-05-18

    Much evidence suggests that the positive association between meat intake and colorectal adenoma (CRA) and cancer (CRC) risk is mediated by mutagenic compounds generated during cooking at high temperature. A number of epidemiological studies have estimated the effect of meat-related mutagens intake on CRC/CRA risk with contradictory and sometimes inconsistent results. A literature search was carried out (PubMed, Web of Science and Scopus) to identify articles reporting the relationship between the intake of meat-related mutagens (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline: DiMeIQx, benzo(a) pyrene (B(a)P) and "meat derived mutagenic activity" (MDM)) and CRC/CRA risk. A random-effect model was used to calculate the risk association. Thirty-nine studies were included in the systematic review and meta-analysis. Polled CRA risk (15229 cases) was significantly increased by intake of PhIP (OR = 1.20; 95% CI: 1.13,1.28; p < 0.001), MeIQx (OR = 1.14; 95% CI: 1.05,1.23; p = 0.001), DiMeIQx (OR = 1.13; 95% CI: 1.05,1.21; p = 0.001), B(a)P (OR = 1.10; 95% CI: 1.02,1.19; p = 0.017) and MDM (OR = 1.17; 95% CI: 1.07,1.28; p = 0.001). A linear and curvilinear trend was observed in dose-response meta-analysis between CRA risk in association with PhIP, MDM, and MeIQx. CRC risk (21,344 cases) was increased by uptake of MeIQx (OR = 1.14; 95% CI: 1.04,1.25; p = 0.004), DiMeIQx (OR = 1.12; 95% CI: 1.02,1.22; p = 0.014) and MDM (OR = 1.12; 95% CI: 1.06,1.19; p < 0.001). No publication bias could be detected, whereas heterogeneity was in some cases rather high. Mutagenic compounds formed during cooking of meat at high temperature may be responsible of its carcinogenicity.

  7. Mutagenicity of New Lead Compounds to Treat Sickle Cell Disease Symptoms in a Salmonella/Microsome Assay

    PubMed Central

    dos Santos, Jean Leandro; Varanda, Eliana A.; Lima, Lídia Moreira; Chin, Chung Man

    2010-01-01

    A series of phthalimide derivatives planned as drugs candidates to treat the symptoms of sickle cell anemia were evaluated in a mutagenicity test using strains of Salmonella typhimurium TA100 and TA102, without and with addition of S9 mixture, with the aim to identify the best structural requirements for a drug candidate without genotoxic activity. The compounds (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl nitrate (1); (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl nitrate (2); 3-(1,3-dioxo-1,3-dihydro-2H-iso-indol-2-yl)benzyl nitrate (3); 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-hydroxy-benzenesulfonamide (4); 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)benzyl nitrate (5) and 2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)phenyl]ethyl nitrate (6) presented mutagenic potency ranging between 0–4,803 revertants/μmol. These results allowed us to propose that a methyl spacer linked to a nitrate ester subunit associated to meta aromatic substitution decreases mutagenicity. PMID:20386668

  8. Characterization and validation of an in silico toxicology model to predict the mutagenic potential of drug impurities*

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Valerio, Luis G., E-mail: luis.valerio@fda.hhs.gov; Cross, Kevin P.

    Control and minimization of human exposure to potential genotoxic impurities found in drug substances and products is an important part of preclinical safety assessments of new drug products. The FDA's 2008 draft guidance on genotoxic and carcinogenic impurities in drug substances and products allows use of computational quantitative structure–activity relationships (QSAR) to identify structural alerts for known and expected impurities present at levels below qualified thresholds. This study provides the information necessary to establish the practical use of a new in silico toxicology model for predicting Salmonella t. mutagenicity (Ames assay outcome) of drug impurities and other chemicals. We describemore » the model's chemical content and toxicity fingerprint in terms of compound space, molecular and structural toxicophores, and have rigorously tested its predictive power using both cross-validation and external validation experiments, as well as case studies. Consistent with desired regulatory use, the model performs with high sensitivity (81%) and high negative predictivity (81%) based on external validation with 2368 compounds foreign to the model and having known mutagenicity. A database of drug impurities was created from proprietary FDA submissions and the public literature which found significant overlap between the structural features of drug impurities and training set chemicals in the QSAR model. Overall, the model's predictive performance was found to be acceptable for screening drug impurities for Salmonella mutagenicity. -- Highlights: ► We characterize a new in silico model to predict mutagenicity of drug impurities. ► The model predicts Salmonella mutagenicity and will be useful for safety assessment. ► We examine toxicity fingerprints and toxicophores of this Ames assay model. ► We compare these attributes to those found in drug impurities known to FDA/CDER. ► We validate the model and find it has a desired predictive performance.« less

  9. [Mutagenicity study of water samples from a waterworks taking Yangtze River as its water source in Jiangsu Province].

    PubMed

    Xiao, Sanhua; Luo, Lan; Qiao, Qian; Lü, Xuemin; Wang, Yanhui; Feng, Lin; Tang, Fei; Wang, Haiyong; Bie, Nana; Wang, Yuehong

    2017-05-01

    To understand the occurrence and change of mutagencity of water samples in the process of drinking water treatment and distribution in a waterworks taking Yangtze River as its water source in Jiangsu Province. Large volume of inlet water, finished water and tap water samples were extracted by XAD-2 resin. Mutagencities were assessed by Ames test and a mutation ratio( MR) of 2 or greater was judged as a positive result. Compared with the samples with S9, samples without S9 presented more positive results( P = 0. 005). That water treatment elevated MR values( P = 0. 007) while the pipe transport made MR values down( P = 0. 038) was observed in samples without S9. The tap water showed weaker mutagenicities than the raw water in samples with S9( P = 0. 008). Compared to the raw water samples, the finished water samples showed more positive results(-S9) and lower MR values( + S9, P =0. 002). Significant mutagenicities of water samples from the Yangtze Riverand its processed water were presented, and frame shit and direct mutagens deserved special concern.

  10. Meat and meat-mutagen intake and pancreatic cancer risk in the NIH-AARP cohort.

    PubMed

    Stolzenberg-Solomon, Rachael Z; Cross, Amanda J; Silverman, Debra T; Schairer, Catherine; Thompson, Frances E; Kipnis, Victor; Subar, Amy F; Hollenbeck, Albert; Schatzkin, Arthur; Sinha, Rashmi

    2007-12-01

    Meat intake, particularly red meat, has been positively associated with pancreatic cancer in some epidemiologic studies. Detailed meat-cooking methods and related mutagens formed in meat cooked at high temperatures have not been evaluated prospectively as risk factors for this malignancy. We investigated the association between meat, meat-cooking methods, meat-mutagen intake, and exocrine pancreatic cancer in the NIH-American Association of Retired Persons (NIH-AARP) Diet and Health Study cohort of 537,302 individuals, aged 50 to 71 years, with complete baseline dietary data (1995-1996) ascertained from a food frequency questionnaire. A meat-cooking module was completed by 332,913 individuals 6 months after baseline. During 5 years of follow-up, 836 incident pancreatic cancer cases (555 men, 281 women) were identified. Four hundred and fifty-nine cases had complete meat module data. We used Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI). Total, red, and high-temperature cooked meat intake was positively associated with pancreatic cancer among men (fifth versus first quintile: HR, 1.41, 95% CI, 1.08-1.83, P trend = 0.001; HR, 1.42, 95% CI, 1.05-1.91, P trend = 0.01; and HR, 1.52, 95% CI, 1.12-2.06, P trend = 0.005, respectively), but not women. Men showed significant 50% increased risks for the highest tertile of grilled/barbecued and broiled meat and significant doubling of risk for the highest quintile of overall meat-mutagenic activity (P trends < 0.01). The fifth quintile of the heterocyclic amine, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline intake showed a significant 29% (P trend = 0.006) increased risk in men and women combined. These findings support the hypothesis that meat intake, particularly meat cooked at high temperatures and associated mutagens, may play a role in pancreatic cancer development.

  11. Acute biotoxic effect of styrene on rat liver. Correlation with enzyme-mediated mutagenicity of benzpyrene and acrylonitrile.

    PubMed

    Roberfroid, M; Poncelet, F; Lambotte-Vandepaer, M; Duverger-Van Bogaert, M; de Meester, C; Mercier, M

    1978-01-01

    Styrene is commonly used in western Europe for the manufacture of plastics suitable for packaging foodstuffs. This report demonstrates that, injected intraperitoneally at a dose as low as 10 mg/kg, styrene modifies the catalytic properties of aryl hydrocarbon hydroxylase by reducing its KM value. A similar effect is reported for two potent chemical carcinogens, 3-methylcholanthrene and benzo(a)pyrene. Ethylbenzene and benzo(e)pyrene and phenobarbital do not produce the same effect. Pretreatments of the rats with chemicals which modify aryl hydrocarbon hydroxylase also increase the capacity of the liver enzymes to activate benzopyrene to a mutagenic intermediate in vitro, as measured by the Ames test for mutagenicity. Exposure to both styrene and the other modifiers of the xenobiotic-metabolizing enzymes could thus influence the carcinogenic and toxic effects of chemicals which are activated by these enzymes. This hypothesis needs further investigation.

  12. Mutagenic and Cytotoxicity LQB 123 Profile: Safety and Tripanocidal Effect of a Phenyl-t-Butylnitrone Derivative

    PubMed Central

    Cupello, Mauricio Peixoto; Saraiva, Francis Monique; Ippolito, Pedro; Fernandes, Andréia da Silva; Costa, Debora de Sousa dos Santos; Paula, Jessica Isis Oliveira; Costa, Paulo Roberto Ribeiro; Dias, Ayres Guimarães

    2017-01-01

    The therapeutic options for Chagas disease are limited and its treatment presents a number of drawbacks including toxicity, drug resistance, and insufficient effectiveness against the chronic stage of the disease. Therefore, new therapeutical options are mandatory. In the present work, we evaluated the effect of a phenyl-tert-butylnitrone (PBN) derivate, LQB 123, against Trypanosoma cruzi forms. LQB 123 presented a trypanocidal effect against bloodstream trypomastigotes (IC50 = 259.4 ± 6.1 μM) and intracellular amastigotes infecting peritoneal macrophages (IC50 = 188.2 ± 47.5 μM), with no harmful effects upon the mammalian cells (CC50 values greater than 4 mM), resulting in a high selectivity index (CC50/IC50 > 20). Additionally, metacyclic trypomastigotes submitted to LQB 123 presented an IC50 of about 191.8 ± 10.5 μM and epimastigotes forms incubated with different concentrations of LQB 123 presented an inhibition of parasite growth with an IC50 of 255.1 ± 3.6 μM. Finally, we investigated the mutagenic potential of the nitrone by the Salmonella/microsome assay and observed no induction of mutagenicity even in concentrations as high as 33000 μM. Taken together, these results present a nonmutagenic compound, with trypanocidal activity against all relevant forms of T. cruzi, offering new insights into CD treatment suggesting additional in vivo tests. PMID:28316976

  13. Mutagenic and Cytotoxicity LQB 123 Profile: Safety and Tripanocidal Effect of a Phenyl-t-Butylnitrone Derivative.

    PubMed

    Cupello, Mauricio Peixoto; Saraiva, Francis Monique; Ippolito, Pedro; Fernandes, Andréia da Silva; Menna-Barreto, Rubem Figueiredo Sadoko; Costa, Debora de Sousa Dos Santos; Paula, Jessica Isis Oliveira; Costa, Paulo Roberto Ribeiro; Nogueira, Natália Pereira; Felzenswalb, Israel; Dias, Ayres Guimarães; Paes, Marcia Cristina

    2017-01-01

    The therapeutic options for Chagas disease are limited and its treatment presents a number of drawbacks including toxicity, drug resistance, and insufficient effectiveness against the chronic stage of the disease. Therefore, new therapeutical options are mandatory. In the present work, we evaluated the effect of a phenyl- tert -butylnitrone (PBN) derivate, LQB 123, against Trypanosoma cruzi forms. LQB 123 presented a trypanocidal effect against bloodstream trypomastigotes (IC 50 = 259.4 ± 6.1  μ M) and intracellular amastigotes infecting peritoneal macrophages (IC 50 = 188.2 ± 47.5  μ M), with no harmful effects upon the mammalian cells (CC 50 values greater than 4 mM), resulting in a high selectivity index (CC 50 /IC 50 > 20). Additionally, metacyclic trypomastigotes submitted to LQB 123 presented an IC 50 of about 191.8 ± 10.5  μ M and epimastigotes forms incubated with different concentrations of LQB 123 presented an inhibition of parasite growth with an IC 50 of 255.1 ± 3.6  μ M. Finally, we investigated the mutagenic potential of the nitrone by the Salmonella /microsome assay and observed no induction of mutagenicity even in concentrations as high as 33000  μ M. Taken together, these results present a nonmutagenic compound, with trypanocidal activity against all relevant forms of T. cruzi , offering new insights into CD treatment suggesting additional in vivo tests.

  14. Reduction of hexavalent chromium by fasted and fed human gastric fluid. I. Chemical reduction and mitigation of mutagenicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    De Flora, Silvio, E-mail: sdf@unige.it

    Evaluation of the reducing capacity of human gastric fluid from healthy individuals, under fasted and fed conditions, is critical for assessing the cancer hazard posed by ingested hexavalent chromium [Cr(VI)] and for developing quantitative physiologically-based pharmacokinetic models used in risk assessment. In the present study, the patterns of Cr(VI) reduction were evaluated in 16 paired pre- and post-meal gastric fluid samples collected from 8 healthy volunteers. Human gastric fluid was effective both in reducing Cr(VI), as measured by using the s-diphenylcarbazide colorimetric method, and in attenuating mutagenicity in the Ames test. The mean (± SE) Cr(VI)-reducing ability of post-meal samplesmore » (20.4 ± 2.6 μg Cr(VI)/mL gastric fluid) was significantly higher than that of pre-meal samples (10.2 ± 2.3 μg Cr(VI)/mL gastric fluid). When using the mutagenicity assay, the decrease of mutagenicity produced by pre-meal and post-meal samples corresponded to reduction of 13.3 ± 1.9 and 25.6 ± 2.8 μg Cr(VI)/mL gastric fluid, respectively. These data are comparable to parallel results conducted by using speciated isotope dilution mass spectrometry. Cr(VI) reduction was rapid, with > 70% of total reduction occurring within 1 min and 98% of reduction is achieved within 30 min with post-meal gastric fluid at pH 2.0. pH dependence was observed with decreasing Cr(VI) reducing capacity at higher pH. Attenuation of the mutagenic response is consistent with the lack of DNA damage observed in the gastrointestinal tract of rodents following administration of ≤ 180 ppm Cr(VI) for up to 90 days in drinking water. Quantifying Cr(VI) reduction kinetics in the human gastrointestinal tract is necessary for assessing the potential hazards posed by Cr(VI) in drinking water. - Highlights: • Cr(VI) reduction capacity was greater in post-meal than paired pre-meal samples. • Cr(VI) reduction was rapid, pH dependent, and due to heat stable components. • Gastric fluid

  15. Mutagenic screening of some commonly used medicinal plants in Nigeria.

    PubMed

    Akintonwa, Alade; Awodele, Olufunsho; Afolayan, Gbenga; Coker, Herbert A B

    2009-09-25

    The uses of medicinal plants have always been part of human culture. The World Health Organization estimates that up to 80% of the world's population relies on traditional medicinal system for some aspect of primary health care. However, there are few reports on the toxicological properties of most medicinal plants especially, their mutagenicity and carcinogenicity. Therefore, this research is to determine the mutagenic potentials of Morinda lucida [Oruwo (Root)], Azadirachta indica [Dongoyaro (Leaf)], Terapluera tetraptera [Aridan (Fruit)], Plumbago zeylanica [Inabiri (Root)], Xylopia aethiopica [Erunje (Fruit)], Newbouldia laevis [Akoko (Leaf)], Alstonia boonei [Ahun (Bark)], Enantia chlorantha [Awopa (Bark)], and Rauvolfia vomitoria [Asofeyeje (Root)] using the Allium cepa Linn. model and the modified Ames assay. Allium cepa model was used to determine the mean root length, mitotic index and chromosomal aberrations effects of these plants on onion bulbs using 0.1, 1, 5 and 10mg/ml concentration of the plant extracts. The modified Ames test which is a modification of the standard Ames test as described by Ames et al. [Ames, B.N., McCann, J., Yamasaki, E., 1975. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian microsome mutagenicity test. Mutation Research 31, 347-364] was done using Escherichia coli (0157:H7) that has the phenotypic characteristics of glucose and lactose fermentation, motile, urease negative, indole positive and citrate negative. The results obtained from Allium cepa assay showed increasing root growth inhibition with increased concentration, decreasing mitotic index with increased concentration and chromosomal aberrations. The modified Ames test showed an alteration in the biochemical characteristics of Escherichia coli (0157:H7) for all plants except Rauvolfia vomitoria and Plumbago zeylanica. Three of the medicinal plants altered at least three of the normal biochemical characteristics thus demonstrating mutagenic

  16. Estimation of the contribution of ultrafine particles to lung deposition of particle-bound mutagens in the atmosphere.

    PubMed

    Kawanaka, Youhei; Matsumoto, Emiko; Sakamoto, Kazuhiko; Yun, Sun-Ja

    2011-02-15

    The present study was performed to estimate the contributions of fine and ultrafine particles to the lung deposition of particle-bound mutagens in the atmosphere. This is the first estimation of the respiratory deposition of atmospheric particle-bound mutagens. Direct and S9-mediated mutagenicity of size-fractionated particulate matter (PM) collected at roadside and suburban sites was determined by the Ames test using Salmonella typhimurium strain TA98. Regional deposition efficiencies in the human respiratory tract of direct and S9-mediated mutagens in each size fraction were calculated using the LUDEP computer-based model. The model calculations showed that about 95% of the lung deposition of inhaled mutagens is caused by fine particles for both roadside and suburban atmospheres. Importantly, ultrafine particles were shown to contribute to the deposition of mutagens in the alveolar region of the lung by as much as 29% (+S9) and 26% (-S9) for the roadside atmosphere and 11% (+S9) and 13% (-S9) for the suburban atmosphere, although ultrafine particles contribute very little to the PM mass concentration. These results indicated that ultrafine particles play an important role as carriers of mutagens into the lung. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Mutagenic and clastogenic properties of 3-chloro-4-(dichloromethyl)-5-hydroxy-2 (5H)-furanone: a potent bacterial mutagen in drinking water

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Meier, J.R.; Blazak, W.F.; Knohl, R.B.

    1987-01-01

    3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) was found to be a direct-acting mutagen in the Ames test for strains TA1535, TA1538, TA92, TA97, TA98, TA100 and TA102. The highest mutagenic response (approximately 13,000 revertants/nmol) was seen in strain TA100. The TA100 response was six- to tenfold higher than in TA98, TA97, and TA102, and 100- to 500-fold higher than in TA1535, TA92, and TA1538. The addition of a 9,000 x g supernatant fraction (S-9) from livers of polychlorinated biphenyl-treated rats, along with cofactors for NADPH generation, resulted in a 90% reduction in the TA100 mutagenicity. MX induced chromosomal aberrations in Chinese hamster ovary cellsmore » after 6-8 hr exposure without S-9 at a dose as low as 4 micrograms/ml, and after 2 hr exposure with S-9 at a dose of 75 micrograms/ml. The oral dose of MX lethal to 50% (LD50) in Swiss-Webster mice was determined to be 128 mg/kg. MX did not induce micronuclei in mouse bone marrow when administered by oral gavage at doses up to 70% of the LD50.« less

  18. From the Cover: An Investigation of the Genotoxicity and Interference of Gold Nanoparticles in Commonly Used In Vitro Mutagenicity and Genotoxicity Assays.

    PubMed

    George, Jiya M; Magogotya, Millicent; Vetten, Melissa A; Buys, Antoinette V; Gulumian, Mary

    2017-03-01

    The suitability of 4 in vitro assays, commonly used for mutagenicity and genotoxicity assessment, was investigated in relation to treatment with 14 nm citrate-stabilized gold nanoparticles (AuNPs). Specifically, the Ames test was conducted without metabolic activation, where no mutagenic effects were observed. High resolution transmission electron microscopy and Cytoviva dark-field image analysis showed that AuNPs did not enter the bacterial cells, thus confirming the unreliability of the Ames test for nanoparticle mutagenicity studies. In addition, the Chinese hamster ovary (CHO) cell line was used for Comet, Chromosome aberration and Micronucleus assays. CHO cells were treated with AuNPs for 20 h at 37 °C. Cytotoxicity was not detected by cell impedance studies even though AuNP uptake was confirmed using Cytoviva image analysis. The DNA damage was statistically significant in treated cells when assessed by the Comet assay. However, minimal and nonstatistically significant chromosomal DNA damage was observed using the chromosome aberration and micronucleus assays. In this study, we showed that false positive results obtained with Comet assay may have been due to the possibility of direct contact between the residual, intracellular AuNPs and DNA during the assay procedure. Therefore, the chromosome aberration and micronucleus assays are better suited to assess the genotoxic effects of nanoparticles due to low probability of such direct contact occurring. Genotoxic effect of 14 and 20 nm citrate-stabilized, as well as, 14 nm PCOOH AuNPs were also investigated using chromosome aberration and micronucleus assays. Based on our acceptance criteria for a positive genotoxic response, none of the AuNPs were found to be genotoxic in either of these assays. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. EFFECT OF THE DECHLORINATING AGENT, ASCORBIC ACID, ON THE MUTAGENICITY OF CHLORINATED WATER SAMPLES

    EPA Science Inventory

    XAD resin adsorption has been widely used to concentrate the organic compounds present in chlorinated drinking waters prior to mutagenicity testing. Previous work has shown that mutagenic artifcats can arise due to the reaction of residual chlorine with the resins. Althrough the ...

  20. Effectivity of advanced wastewater treatment: reduction of in vitro endocrine activity and mutagenicity but not of in vivo reproductive toxicity.

    PubMed

    Giebner, Sabrina; Ostermann, Sina; Straskraba, Susanne; Oetken, Matthias; Oehlmann, Jörg; Wagner, Martin

    2018-02-01

    Conventional wastewater treatment plants (WWTPs) have a limited capacity to eliminate micropollutants. One option to improve this is tertiary treatment. Accordingly, the WWTP Eriskirch at the German river Schussen has been upgraded with different combinations of ozonation, sand, and granulated activated carbon filtration. In this study, the removal of endocrine and genotoxic effects in vitro and reproductive toxicity in vivo was assessed in a 2-year long-term monitoring. All experiments were performed with aqueous and solid-phase extracted water samples. Untreated wastewater affected several endocrine endpoints in reporter gene assays. The conventional treatment removed the estrogenic and androgenic activity by 77 and 95 %, respectively. Nevertheless, high anti-estrogenic activities and reproductive toxicity persisted. All advanced treatment technologies further reduced the estrogenic activities by additional 69-86 % compared to conventional treatment, resulting in a complete removal of up to 97 %. In the Ames assay, we detected an ozone-induced mutagenicity, which was removed by subsequent filtration. This demonstrates that a post treatment to ozonation is needed to minimize toxic oxidative transformation products. In the reproduction test with the mudsnail Potamopyrgus antipodarum, a decreased number of embryos was observed for all wastewater samples. This indicates that reproductive toxicants were eliminated by neither the conventional nor the advanced treatment. Furthermore, aqueous samples showed higher anti-estrogenic and reproductive toxicity than extracted samples, indicating that the causative compounds are not extractable or were lost during extraction. This underlines the importance of the adequate handling of wastewater samples. Taken together, this study demonstrates that combinations of multiple advanced technologies reduce endocrine effects in vitro. However, they did not remove in vitro anti-estrogenicity and in vivo reproductive toxicity. This

  1. Tautomerism provides a molecular explanation for the mutagenic properties of the anti-HIV nucleoside 5-aza-5,6-dihydro-2'-deoxycytidine.

    PubMed

    Li, Deyu; Fedeles, Bogdan I; Singh, Vipender; Peng, Chunte Sam; Silvestre, Katherine J; Simi, Allison K; Simpson, Jeffrey H; Tokmakoff, Andrei; Essigmann, John M

    2014-08-12

    Viral lethal mutagenesis is a strategy whereby the innate immune system or mutagenic pool nucleotides increase the error rate of viral replication above the error catastrophe limit. Lethal mutagenesis has been proposed as a mechanism for several antiviral compounds, including the drug candidate 5-aza-5,6-dihydro-2'-deoxycytidine (KP1212), which causes A-to-G and G-to-A mutations in the HIV genome, both in tissue culture and in HIV positive patients undergoing KP1212 monotherapy. This work explored the molecular mechanism(s) underlying the mutagenicity of KP1212, and specifically whether tautomerism, a previously proposed hypothesis, could explain the biological consequences of this nucleoside analog. Establishing tautomerism of nucleic acid bases under physiological conditions has been challenging because of the lack of sensitive methods. This study investigated tautomerism using an array of spectroscopic, theoretical, and chemical biology approaches. Variable temperature NMR and 2D infrared spectroscopic methods demonstrated that KP1212 existed as a broad ensemble of interconverting tautomers, among which enolic forms dominated. The mutagenic properties of KP1212 were determined empirically by in vitro and in vivo replication of a single-stranded vector containing a single KP1212. It was found that KP1212 paired with both A (10%) and G (90%), which is in accord with clinical observations. Moreover, this mutation frequency is sufficient for pushing a viral population over its error catastrophe limit, as observed before in cell culture studies. Finally, a model is proposed that correlates the mutagenicity of KP1212 with its tautomeric distribution in solution.

  2. OVERVIEW OF THE MUTAGENICITY OF URBAN AIR

    EPA Science Inventory

    For the past 25 years, there has been great interest in the mutagenicity and carcinogenicity of ambient air and in the sources of those genotoxicants. Prior to the 1980's, the evaluation of airborne toxicants was done on a pollutant-by-pollutant basis. However, the assessment of ...

  3. Meat mutagens and breast cancer in postmenopausal women -a cohort analysis

    PubMed Central

    Wu, Kana; Sinha, Rashmi; Holmes, Michelle D.; Giovannucci, Edward; Willett, Walter; Cho, Eunyoung

    2011-01-01

    Background Mutagenic compounds produced when meats are cooked at high temperatures have been hypothesized to increase risk of breast cancer. Methods We examined the association between intakes of the heterocyclic amines (HCAs) MeIQx (2-amino-3,8-dimethylimidazo (4,5,-f) quinoxaline), PhIP (2-amino-1-methyl-6-phenylimidazo (4,5-b) pyridine), DiMeIQx (2-amino-3,4,8-trimethylimidazo (4,5,-f)) and meat-derived mutagenic activity (MDM) and risk of breast cancer using a cooking method questionnaire administered in 1996 in the Nurses Health Study. Between 1996 and 2006, 2,317 breast cancer cases were diagnosed during 533,618 person years. Results Higher intake of HCAs or MDM was not associated with elevated risk of breast cancer (multivariate relative risk (RR) and 95% confidence interval (95% CI) for the highest vs. lowest quintile: MeIQx: 0.90 (0.79–1.03); PhIP: 0.92 (0.80–1.05); DiMeIQx: 0.92 (0.80–1.05) and MDM: 0.98 (0.85–1.12)). HCA or MDM were not associated with estrogen receptor positive/progesterone positive breast cancer risk either. There was some suggestion of a decreased risk of estrogen receptor negative/progesterone receptor negative breast cancer with higher intakes of MeIQx, DiMeIQx and PhIP, but none of the associations were statistically significant. There was little evidence for an interaction between intake of cruciferous vegetables and HCA or MDM intake and risk of breast cancer. Conclusion Higher consumption of mutagens from meats cooked at higher temperature and longer duration was not associated with increased risk of postmenopausal breast cancer. Impact Overall prospective data including results from our study do not provide support for a substantial increase in risk of breast cancer with higher intake of HCAs. PMID:20447922

  4. Intake of meat, meat mutagens, and iron and the risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

    PubMed

    Ferrucci, L M; Cross, A J; Graubard, B I; Brinton, L A; McCarty, C A; Ziegler, R G; Ma, X; Mayne, S T; Sinha, R

    2009-07-07

    Epidemiological evidence on meat intake and breast cancer is inconsistent, with little research on potentially carcinogenic meat-related exposures. We investigated meat subtypes, cooking practices, meat mutagens, iron, and subsequent breast cancer risk. Among 52 158 women (aged 55-74 years) in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, who completed a food frequency questionnaire, 1205 invasive breast cancer cases were identified. We estimated meat mutagen and haem iron intake with databases accounting for cooking practices. Using Cox proportional hazards regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) within quintiles of intake. Comparing the fifth to the first quintile, red meat (HR=1.23; 95% CI=1.00-1.51, P trend=0.22), the heterocyclic amine (HCA), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), (HR=1.26; 95% CI=1.03-1.55; P trend=0.12), and dietary iron (HR=1.25; 95% CI=1.02-1.52; P trend=0.03) were positively associated with breast cancer. We observed elevated, though not statistically significant, risks with processed meat, the HCA 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), mutagenic activity, iron from meat, and haem iron from meat. In this prospective study, red meat, MeIQx, and dietary iron elevated the risk of invasive breast cancer, but there was no linear trend in the association except for dietary iron.

  5. Intake of meat, meat mutagens, and iron and the risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

    PubMed Central

    Ferrucci, L M; Cross, A J; Graubard, B I; Brinton, L A; McCarty, C A; Ziegler, R G; Ma, X; Mayne, S T; Sinha, R

    2009-01-01

    Background: Epidemiological evidence on meat intake and breast cancer is inconsistent, with little research on potentially carcinogenic meat-related exposures. We investigated meat subtypes, cooking practices, meat mutagens, iron, and subsequent breast cancer risk. Methods: Among 52 158 women (aged 55–74 years) in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, who completed a food frequency questionnaire, 1205 invasive breast cancer cases were identified. We estimated meat mutagen and haem iron intake with databases accounting for cooking practices. Using Cox proportional hazards regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) within quintiles of intake. Results: Comparing the fifth to the first quintile, red meat (HR=1.23; 95% CI=1.00–1.51, P trend=0.22), the heterocyclic amine (HCA), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), (HR=1.26; 95% CI=1.03–1.55; P trend=0.12), and dietary iron (HR=1.25; 95% CI=1.02–1.52; P trend=0.03) were positively associated with breast cancer. We observed elevated, though not statistically significant, risks with processed meat, the HCA 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), mutagenic activity, iron from meat, and haem iron from meat. Conclusion: In this prospective study, red meat, MeIQx, and dietary iron elevated the risk of invasive breast cancer, but there was no linear trend in the association except for dietary iron. PMID:19513076

  6. Evaluation of Antitrypanosomal Dihydroquinolines for Hepatotoxicity, Mutagenicity, and Methemoglobin Formation In Vitro

    PubMed Central

    Werbovetz, Karl A.; Riccio, Edward S.; Furimsky, Anna; Richard, Julian V.; He, Shanshan; Iyer, Lalitha; Mirsalis, Jon

    2014-01-01

    N 1-benzylated dihydroquinolin-6-ols and their corresponding esters display exceptional activity against African trypanosomes in vitro, and administration of members of this class of compounds to trypanosome-infected mice results in cures in a first stage African trypanosomiasis model. Since a quinone imine intermediate has been implicated in the antiparasitic mechanism of action of these compounds, evaluation of the hepatotoxic, mutagenic, and methemoglobin-promoting effects of these agents was performed. 1-Benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-ol hydrochloride (OSU-36.HCl) and 1-benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate (OSU-40) showed outstanding in vitro selectivity for T. brucei compared to the HepG2, Hep3B, Huh7 and PLC5 hepatocyte cell lines. OSU-36.HCl and 1-(2-methoxybenzyl)-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate (OSU-75) were not mutagenic when screened in the Ames assay, with or without metabolic activation. The latter two compounds promoted time- and dose-dependent formation of methemoglobin when incubated in whole human blood, but such levels were below those typically required to produce symptoms of methemoglobinemia in humans. While compounds capable of quinone imine formation require careful evaluation, these in vitro studies indicate that antitrypanosomal dihydroquinolines merit further study as drug candidates against the neglected tropical disease human African trypanosomiasis. PMID:24819520

  7. Halogenated 2,5-pyrrolidinediones: synthesis, bacterial mutagenicity in Ames tester strain TA-100 and semi-empirical molecular orbital calculations.

    PubMed

    Freeman, B A; Wilson, R E; Binder, R G; Haddon, W F

    2001-02-20

    The chloroimide 3,3-dichloro-4-(dichloromethylene)-2,5-pyrrolidinedione, a tetrachloroitaconimide, is the principal mutagen produced by chlorination of simulated poultry chiller water. It is the second most potent mutagenic disinfection by-product of chlorination ever reported. Six of seven new synthetic analogs of this compound are direct-acting mutagens in Ames tester strain TA-100. Computed energies of the lowest unoccupied molecular orbital (E(LUMO)) and of the radical anion stability (DeltaH(f)(rad)-DeltaH(f)) from MNDO-PM3 for the chloroimides show a quantitative correlation with the Ames TA-100 bacterial mutagenicity values. The molar mutagenicities of these direct acting mutagenic imides having an exocyclic double bond fit the same linear correlation (lnM(m) vs. E(LUMO); lnM(m) vs. DeltaH(f)(rad)--DeltaH(f)) as the chlorinated 2(5H)-furanones, including the potent mutagen MX, 3-chloro-4-(dichloro-methyl)-5-hydroxy-2(5H)-furanone, a by-product of water chlorination and paper bleaching with chlorine. Mutagenicity data for related haloimides having endocyclic double bonds are also given. For the same number of chlorine atoms, the imides with endocyclic double bonds have significantly higher Ames mutagenicity compared to their structural analogs with exocyclic double bonds, but do not follow the same E(LUMO) or DeltaH(f)(rad)-DeltaH(f) correlation as the exocyclic chloroimides and the chlorinated 2(5H)-furanones.

  8. Assessment of sediment mutagenicity in areas under the influence of a contaminated site undergoing a remediation process.

    PubMed

    Gameiro, Paula Hauber; Pereira, Naiara Costa; Rocha, Jocelita Aparecida Vaz; Leal, Karen Alam; Vargas, Vera Maria Ferrão

    2018-04-10

    Soil contamination enters aquatic ecosystems affecting sediment quality. The region studied is the Taquari River, Brazil, close to a site contaminated by wood preservatives, with a runoff route into the river. The first stage of the remediation process (In this article, the terms intervention and remediation have been used with slightly different meanings. We consider intervention to be the first phase of the remediation process, which aims to remove active sources) was an intervention to remove the main active sources. The Salmonella/microsome assay and polycyclic aromatic hydrocarbons (PAHs) were used to assess sediment quality in organic extracts during different intervention phases. The strains used were TA98, TA97a, and TA100 with and without S9mix (±S9). The results indicated the presence of pro-mutagens at site Ta010 (closest to the contaminated site) in all samplings, and the highest result occurred before intervention for TA100 + S9 (1,672 ± 215.9 rev/g). These values decreased during (83 ± 23.6 rev/g) and after this process (403 ± 105.9 rev/g), although the PAHs concentrations increased. Samples from this site presented PAHs with a carcinogenic potential during the assessed periods. After intervention, Ta006 (4 km downstream from Ta010) showed the most significant mutagenesis for TA100 + S9 (764 ± 230.2 rev/g) and, although the total PAHs values were lower, the species considered carcinogenic had higher concentrations. Mutagenesis predicted values of PAHs confirmed that carcinogenic species were predominantly detected by TA100, and the other PAHs by TA97a strains. Marked contaminant release to the river was observed, mainly in Ta010 at different periods. Mutagenicity and PAHs values in an internal stream, upstream from Ta010, showed a dispersion route of these agents. Thus, contamination in Ta010 and possible contribution to Ta006, after intervention, provides a warning regarding environmental quality in the region. Environ

  9. [Usefulness of the fruit fly for assessment of mutagenicity of benzene, acetaldehyde and formaldehyde].

    PubMed

    Krogulski, A

    1994-01-01

    Among the contaminants of water, soil and air the number of mutagenic and carcinogenic substances is increasing. For the assessment of health risk connected with the simple and cheap methods are necessary which could detected and measure the mutagenicity of these substances. The widely used tests using prokaryotes give negative results in the tests of certain substances which are carcinogenic in mammals. In the case of benzene and acetaldehyde Ames test gives false negative results, and in the case of formaldehyde the results are equivocal. An advantage of fruit fly Drosophila melanogaster used for this purpose is that its cell structures, enzymes and metabolic processes are similar to those of mammals. For the demonstration of mutagenicity of benzene, acetaldehyde and formaldehyde the test of somatic mutation and recombination SMART was carried out in these flies. The results confirmed the usefulness of the SMART test for the demonstration of the mutagenicity of contaminants in the environment.

  10. Acute, subacute toxicity and mutagenic effects of anacardic acids from cashew (Anacardium occidentale Linn.) in mice.

    PubMed

    Carvalho, Ana Laura Nicoletti; Annoni, Raquel; Silva, Paula Regina Pereira; Borelli, Primavera; Fock, Ricardo Ambrósio; Trevisan, Maria Teresa Salles; Mauad, Thais

    2011-06-01

    Anacardium occidentale Linn. (cashew) is a Brazilian plant that is usually consumed in natura and is used in folk medicine. Anacardic acids (AAs) in the cashew nut shell liquid are biologically active as gastroprotectors, inhibitors of the activity of various deleterious enzymes, antitumor agents and antioxidants. Yet, there are no reports of toxicity testing to guarantee their use in vivo models. We evaluated AAs biosafety by measuring the acute, subacute and mutagenic effects of AAs administration in BALB/c mice. In acute tests, BALB/c mice received a single oral dose of 2000 mg/kg, whereas animals in subacute tests received 300, 600 and 1000 mg/kg for 30 days. Hematological, biochemical and histological analyses were performed in all animals. Mutagenicity was measured with the acute micronucleus test 24h after oral administration of 250 mg/kg AAs. Our results showed that the AAs acute minimum lethal dose in BALB/c mice is higher than 2000 mg/kg since this concentration did not produce any symptoms. In subacute tests, females which received the highest doses (600 or 1000 mg/kg) were more susceptible, which was seen by slightly decreased hematocrit and hemoglobin levels coupled with a moderate increase in urea. Anacardic acids did not produce any mutagenic effects. The data indicate that doses less than 300 mg/kg did not produce biochemical and hematological alterations in BALB/c mice. Additional studies must be conducted to investigate the pharmacological potential of this natural substance in order to ensure their safe use in vivo. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  11. Cytotoxic, genotoxic and mutagenic evaluation of surface waters from a coal exploration region.

    PubMed

    Porta, Cynthia Silva; Dos Santos, Débora Lemes; Bernardes, Hélio Vieira; Bellagamba, Bruno Corrêa; Duarte, Anaí; Dias, Johnny Ferraz; da Silva, Fernanda Rabaioli; Lehmann, Mauricio; da Silva, Juliana; Dihl, Rafael Rodrigues

    2017-04-01

    Coal mining generates a considerable amount of waste, which is disposed of in piles or dams near mining sites. As a result, leachates may reach rivers and streams, promoting the wide dispersion of contaminants in solution and as particulate matter. The present study evaluated the cytotoxic, genotoxic, and mutagenic action of surface waters collected around a thermoelectric power plant and the largest mining area in Brazil (Candiota). Four sites in Candiota stream were selected, and samples were collected in winter and summer. Water samples were analyzed using the comet and CBMN assays in V79 and HepG2 cells. Furthermore, genotoxicity of water samples was evaluated in vivo using the SMART in Drosophila melanogaster. In addition, polycyclic aromatic hydrocarbons and inorganic elements were quantified. The results indicate that water samples exhibited no genotoxic and mutagenic activities, whether in vitro or in vivo. On the other hand, surface water samples collected in sites near the power plant in both summer and winter inhibited cell proliferation and induced increased frequencies of V79 cell death, apoptosis, and necrosis. The cytotoxicity observed may be associated with the presence of higher concentration of inorganic elements, especially aluminum, silicon, sulfur, titanium and zinc at sites 1 and 2 in the stream, as well as with the complex mixture present in the coal, in both seasons. Therefore, the results obtained point to the toxicity potential of water samples with the influence of coal mining and combustion processes and the possible adverse effects on the health of exposed organisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Probiotic administration effect on fecal mutagenicity and microflora in the goat's gut.

    PubMed

    Apás, Ana Lidia; Dupraz, Javier; Ross, Romina; González, Silvia Nelina; Arena, Mario Eduardo

    2010-11-01

    The application of potentially beneficial microorganisms to increase host defense is a new trend to increase health benefits. In this paper the first specific host probiotics for goats from a mixture isolated from healthy animals (Lactobacillus reuteri DDL 19, Lactobacillus alimentarius DDL 48, Enterococcus faecium DDE 39 and Bifidobacterium bifidum DDBA) was assayed. The effect of probiotic oral administration on goats' weight, gut microbiota, as well as on the production of mutagen compounds and their indicator (putrescine), were evaluated. The probiotic supplement was able to modify microflora balance by reducing Enterobacteria like Salmonella/Shigella (1.09 and 1.21 log CFU/g feces, respectively) and increasing lactic acid bacteria and Bifidobacteria (1.67 and 2.34 log CFU/g feces, respectively). The probiotics administration was correlated with a ten time diminution of fecal putrescine (cancer and bacterial disease marker) and a decrease of 60% mutagen fecal concentration, indicating the protective effect of the treatment. Additionally, a significant increase in ruminant weight was observed after probiotic administration. These results are encouraging towards the use of probiotic mixtures as functional food for goats. Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  13. Fine and ultrafine atmospheric particulate matter at a multi-influenced urban site: Physicochemical characterization, mutagenicity and cytotoxicity.

    PubMed

    Landkocz, Yann; Ledoux, Frédéric; André, Véronique; Cazier, Fabrice; Genevray, Paul; Dewaele, Dorothée; Martin, Perrine J; Lepers, Capucine; Verdin, Anthony; Courcot, Lucie; Boushina, Saâd; Sichel, François; Gualtieri, Maurizio; Shirali, Pirouz; Courcot, Dominique; Billet, Sylvain

    2017-02-01

    Particulate Matter (PM) air pollution is one of the major concerns for environment and health. Understanding the heterogeneity and complexity of fine and ultrafine PM is a fundamental issue notably for the assessment of PM toxicological effects. The aim of this study was to evaluate mutagenicity and cytotoxicity of a multi-influenced urban site PM, with or without the ultrafine fraction. For this purpose, PM 2.5-0.3 (PM with aerodynamic diameter ranging from 0.3 to 2.5 μm) and PM 2.5 were collected in Dunkerque, a French coastal industrial city and were extensively characterized for their physico-chemical properties, including inorganic and organic species. In order to identify the possible sources of atmospheric pollution, specific criteria like Carbon Preference Index (CPI) and PAH characteristic ratios were investigated. Mutagenicity assays using Ames test with TA98, TA102 and YG1041 Salmonella strains with or without S9 activation were performed on native PM sample and PM organic extracts and water-soluble fractions. BEAS-2B cell viability and cell proliferation were evaluated measuring lactate dehydrogenase release and mitochondrial dehydrogenase activity after exposure to PM and their extracts. Several contributing sources were identified in PM: soil resuspension, marine emissions including sea-salt or shipping, road traffic and industrial activities, mainly related to steelmaking or petro-chemistry. Mutagenicity of PM was evidenced, especially for PM 2.5 , including ultrafine fraction, in relation to PAHs content and possibly nitro-aromatics compounds. PM induced cytotoxic effects at relatively high doses, while alteration of proliferation with low PM doses could be related to underlying mechanisms such as genotoxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Evaluation of a statistics-based Ames mutagenicity QSAR model and interpretation of the results obtained.

    PubMed

    Barber, Chris; Cayley, Alex; Hanser, Thierry; Harding, Alex; Heghes, Crina; Vessey, Jonathan D; Werner, Stephane; Weiner, Sandy K; Wichard, Joerg; Giddings, Amanda; Glowienke, Susanne; Parenty, Alexis; Brigo, Alessandro; Spirkl, Hans-Peter; Amberg, Alexander; Kemper, Ray; Greene, Nigel

    2016-04-01

    The relative wealth of bacterial mutagenicity data available in the public literature means that in silico quantitative/qualitative structure activity relationship (QSAR) systems can readily be built for this endpoint. A good means of evaluating the performance of such systems is to use private unpublished data sets, which generally represent a more distinct chemical space than publicly available test sets and, as a result, provide a greater challenge to the model. However, raw performance metrics should not be the only factor considered when judging this type of software since expert interpretation of the results obtained may allow for further improvements in predictivity. Enough information should be provided by a QSAR to allow the user to make general, scientifically-based arguments in order to assess and overrule predictions when necessary. With all this in mind, we sought to validate the performance of the statistics-based in vitro bacterial mutagenicity prediction system Sarah Nexus (version 1.1) against private test data sets supplied by nine different pharmaceutical companies. The results of these evaluations were then analysed in order to identify findings presented by the model which would be useful for the user to take into consideration when interpreting the results and making their final decision about the mutagenic potential of a given compound. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Investigation of styrene in the liver perfusion/cell culture system. No indication of styrene-7,8-oxide as the principal mutagenic metabolite produced by the intact rat liver.

    PubMed

    Beije, B; Jenssen, D

    1982-03-01

    Mutagenic effect of styrene and styrene-7,8-oxide was studied with the isolated perfused rat liver as metabolizing system and Chinese hamster V79 cells as genetic target cells. Styrene-7,8-oxide which is mutagenic per se was rapidly metabolized by the perfused rat liver. Thus no mutagenic effect was detected neither in the perfusion medium nor in the bile. However when styrene was added to the perfusion system, an increase in V79 mutants was observed regardless of where in the circulating perfusion medium the V79 cells were placed: the same effect was obtained with V79 cells close to the liver as well as at a distance from the liver. No mutagenic effect was observed in the bile. Simultaneous analysis of the styrene-7,8-oxide concentration in the perfusion medium, suggest that this metabolite is not the cause of the mutagenic effect observed during perfusion with styrene. The effect of the two test compounds on some liver functions was also studied. Both styrene and styrene-7,8-oxide changed the bile flow without affecting bile acid secretion: styrene caused a reduction in bile flow as compared to control perfusions and styrene-7,8-oxide increased the bile flow. Styrene, but not styrene-7,8-oxide, reduced gluconeogenesis from lactate. Styrene had no effect on the liver's capacity to incorporate amino acids into plasma proteins, whereas styrene-7,8-oxide reduced the amino acid incorporation. The microsomal cytochrome P-450 content was not affected by the two test compounds. No alteration in microsomal N- and C-oxygenation of N,N-dimethylaniline (DMA) was observed with styrene-7,8-oxide or the lower styrene dose used (240 mumol), whereas the higher styrene concentration (480 mumol) reduced N-oxygenation and thus also the total DNA metabolism. It is suggested that the results on styrene and styrene-7,8-oxide found here using the liver perfusion/cell culture system mimic the metabolism expected to be found in the intact animal, thus indicating that styrene-7,8-oxide is

  16. Tautomerism provides a molecular explanation for the mutagenic properties of the anti-HIV nucleoside 5-aza-5,6-dihydro-2′-deoxycytidine

    PubMed Central

    Li, Deyu; Fedeles, Bogdan I.; Singh, Vipender; Peng, Chunte Sam; Silvestre, Katherine J.; Simi, Allison K.; Simpson, Jeffrey H.; Tokmakoff, Andrei; Essigmann, John M.

    2014-01-01

    Viral lethal mutagenesis is a strategy whereby the innate immune system or mutagenic pool nucleotides increase the error rate of viral replication above the error catastrophe limit. Lethal mutagenesis has been proposed as a mechanism for several antiviral compounds, including the drug candidate 5-aza-5,6-dihydro-2′-deoxycytidine (KP1212), which causes A-to-G and G-to-A mutations in the HIV genome, both in tissue culture and in HIV positive patients undergoing KP1212 monotherapy. This work explored the molecular mechanism(s) underlying the mutagenicity of KP1212, and specifically whether tautomerism, a previously proposed hypothesis, could explain the biological consequences of this nucleoside analog. Establishing tautomerism of nucleic acid bases under physiological conditions has been challenging because of the lack of sensitive methods. This study investigated tautomerism using an array of spectroscopic, theoretical, and chemical biology approaches. Variable temperature NMR and 2D infrared spectroscopic methods demonstrated that KP1212 existed as a broad ensemble of interconverting tautomers, among which enolic forms dominated. The mutagenic properties of KP1212 were determined empirically by in vitro and in vivo replication of a single-stranded vector containing a single KP1212. It was found that KP1212 paired with both A (10%) and G (90%), which is in accord with clinical observations. Moreover, this mutation frequency is sufficient for pushing a viral population over its error catastrophe limit, as observed before in cell culture studies. Finally, a model is proposed that correlates the mutagenicity of KP1212 with its tautomeric distribution in solution. PMID:25071207

  17. Adverse Outcome Pathway (AOP) for a Mutagenic Mode of ...

    EPA Pesticide Factsheets

    AOPs provide a framework to describe a sequence of measureable key events (KEs), beginning with a molecular initiating event (MIE), followed by a series of identified KEs linked to one another by KE Relationships (KERs), all anchored by a specific adverse outcome (AO). Each KE/KER is supported by data and evaluated against criteria to assess biological plausibility, weight/strength of evidence, specificity, and confidence. AOPs offer an approach to using toxicological data and predictive modeling to actualize use of mode-of-action (MOA) for such purposes as read-across, integrated approaches to testing & assessment, and risk assessment. Different applications will depend partly on the scientific confidence underpinning each KE/KER and the overall AOP. An OECD program encourages development of AOPs, with a wiki that allows for public review & comment to foster collaborations and broaden understanding & application of AOPs. Developing an AOP for a mutagenic MOA for cancer as a case study in the OECD program lays a path towards determination of such an MOA and its use in chemical assessment programs. Aflatoxin B1 (AFB1), with ubiquitous exposure and a rich database, was selected for this case study. AFB1 has been determined to induce HCC via a DNA-reactive MOA in many species, including humans. The sequential KEs identified for AFB1 are as follows: pre-MIE: Hepatic metabolic activation; MIE: Formation of a pro-mutagenic DNA adduct (N7-AFB1-guanine or AFB1-FAPy); KE

  18. Comparative mutagenicity and genotoxicity of particles and aerosols emitted by the combustion of standard vs. rapeseed methyl ester supplemented bio-diesel fuels: impact of after treatment devices: oxidation catalyst and particulate filter.

    PubMed

    André, V; Barraud, C; Capron, D; Preterre, D; Keravec, V; Vendeville, C; Cazier, F; Pottier, D; Morin, J P; Sichel, F

    2015-01-01

    Diesel exhausts are partly responsible for the deleterious effects on human health associated with urban pollution, including cardiovascular diseases, asthma, COPD, and possibly lung cancer. Particulate fraction has been incriminated and thus largely investigated for its genotoxic properties, based on exposure conditions that are, however, not relevant for human risk assessment. In this paper, original and more realistic protocols were used to investigate the hazards induced by exhausts emitted by the combustion of standard (DF0) vs. bio-diesel fuels (DF7 and DF30) and to assess the impact of exhaust treatment devices (DOC and DPF). Mutagenicity and genotoxicity were evaluated for (1) resuspended particles ("off line" exposure that takes into account the bioavailability of adsorbed chemicals) and for (2) the whole aerosols (particles+gas phase components) under continuous flow exposure ("on line" exposure). Native particles displayed mutagenic properties associated with nitroaromatic profiles (YG1041), whereas PAHs did not seem to be involved. After DOC treatment, the mutagenicity of particles was fully abolished. In contrast, the level of particle deposition was low under continuous flow exposure, and the observed mutagenicity in TA98 and TA102 was thus attributable to the gas phase. A bactericidal effect was also observed in TA102 after DOC treatment, and a weak but significant mutagenicity persisted after DPF treatment for bio-diesel fuels. No formation of bulky DNA-adducts was observed on A549 cells exposed to diesel exhaust, even in very drastic conditions (organic extracts corresponding to 500 μg equivalent particule/mL, 48 h exposure). Taken together, these data indicate that the exhausts issued from the bio-diesel fuels supplemented with rapseed methyl ester (RME), and generated by current diesel engines equipped with after treatment devices are less mutagenic than older ones. The residual mutagenicity is linked to the gas phase and could be due to pro

  19. The mutagenicity of indoor air particles in a residential pilot field study: Application and evaluation of new methodologies

    NASA Astrophysics Data System (ADS)

    Lewtas, Joellen; Goto, Sumio; Williams, Katherine; Chuang, Jane C.; Petersen, Bruce A.; Wilson, Nancy K.

    The mutagenicity of indoor air paniculate matter has been measured in a pilot field study of homes in Columbus, Ohio during the 1984 winter. The study was conducted in eight all natural-gas homes and two all electric homes. Paniculate matter and semi-volatile organic compounds were collected indoors using a medium volume sampler. A micro-forward mutation bioassay employing Salmonella typhimurium strain TM 677 was used to quantify the mutagenicity in solvent extracts of microgram quantities of indoor air particles. The mutagenicity was quantified in terms of both mutation frequency per mg of organic matter extracted and per cubic meter of air sampled. The combustion source variables explored in this study included woodburning in fireplaces and cigarette smoking. Homes in which cigarette smoking occurred had the highest concentrations of mutagenicity per cubic meter of air. The average indoor air mutagenicity per cubic meter was highly correlated with the number of cigarettes smoked. When the separate sampling periods in each room were compared, the mutagenicity in the kitchen samples was the most highly correlated with the number of cigarettes smoked.

  20. Ames Mutagenicity Test of the RDX Replacement, Triaminoguanidinium-1-methyl-5-nitriminotetrazolate (TAG-MNT)

    DTIC Science & Technology

    2010-03-01

    5-nitriminotetrazolate (TAG-MNT) using the Xenometrix Microplate Format Mutagenicity Assay with five strains of bacteria in compliance with the...798.5265.), The U.S. Food and Drug Administration (USFDA) and OCED (OECD, 1997). f. Xenometrix has developed a proprietary microplate format (MPFTM...8217-Azotetrazolate Salts. Chem. Mater. 17(14): 3784-3793. Kasuske, L., J. M. Schofer and K. Hasegawa. 2009. Two marines with generalized seizure activity. J Emerg

  1. Temporal and spatial distribution of particulate carcinogens and mutagens in Bangkok, Thailand.

    PubMed

    Pongpiachan, Siwatt; Choochuay, C; Hattayanone, M; Kositanont, C

    2013-01-01

    To investigate the level of genotoxicity over Bangkok atmosphere, PM10 samples were collected at the Klongchan Housing Authority (KHA), Nonsree High School (NHS), Watsing High School (WHS), Electricity Generating Authority of Thailand (EGAT), Chokchai 4 Police Station (CPS), Dindaeng Housing Authority (DHA) and Badindecha High School (BHS). For all monitoring stations, each sample covered a period of 24 hours taken at a normal weekday every month from January-December 2006 forming a database of 84 individual air samples (i.e. 12?7=84). Atmospheric concentrations of low molecular weight PAHs (i.e. phenanthrene, anthracene, pyrene and fluoranthene) were measured in PM10 at seven observatory sites operated by the pollution control department of Thailand (PCD). The mutagenicity of extracts of the samples was compared in Salmonella according to standard Ames test method. The dependence of the effects on sampling time and on sampling location was investigated with the aid of a calculation of mutagenic index (MI). This MI was used to estimate the increase in mutagenicity above background levels (i.e. negative control) at the seven monitoring sites in urban area of Bangkok due to anthropogenic emissions within that area. Applications of the AMES method showed that the average MI of PM10 collected at all sampling sites were 1.37±0.10 (TA98; +S9), 1.24±0.08 (TA98; -S9), 1.45±0.10 (TA100; +S9) and 1.30±0.09 (TA100; -S9) with relatively less variations. Analytical results reconfirm that the particulate PAH concentrations measured at PCD air quality monitoring stations are moderately low in comparison with previous results observed in other countries. In addition, the concept of incremental lifetime particulate matter exposure (ILPE) was employed to investigate the potential risks of exposure to particulate PAHs in Bangkok atmosphere.

  2. Evaluation of the mutagenic and cytotoxic effects of mercurous chloride by the micronuclei technique in golden Syrian hamsters.

    PubMed

    Cortés-Gutiérrez, Elva I; Cerda-Flores, Ricardo M; González-Ramírez, Diego; Zúñiga-Charles, Miguel A; Lazcano-Martínez, Sigifredo; Sampayo-Reyes, Adriana; Leal-Garza, Carlos H

    2004-05-01

    The aims of this study were to evaluate the mutagenic and cytotoxic activity of mercurous chloride by the micronucleus technique in vivo on the bone marrow of golden Syrian hamsters after a single i.p. drug administration. Forty male golden Syrian hamsters were classified into eight groups: negative control, positive control and six groups treated with different doses of mercurous chloride (1.25, 2.5, 5, 10, 20 and 40 mg/kg). The negative control was injected with physiological saline i.p. and the positive control with cyclophosphamide at a dose of 80 mg/kg i.p. With respect to mutagenic effect, the average number of micronucleated polychromatic erythrocytes (MPE) in hamsters treated with different doses of mercurous chloride was not significant compared with the negative control. With respect to cytotoxic effect, the average polychromatic erythrocyte/red blood cell ratio showed a significant decrease when the doses were higher than the 2.5 mg/kg dose compared with the negative control. In conclusion, this preliminary study shows a cytotoxic effect but not a mutagenic effect of calomel in vivo at one time point (24 h).

  3. Declaring the Existence of Human Germ-Cell Mutagens

    EPA Science Inventory

    After more than 80 years of searching for human germ-cell mutagens, I think that sufficient evidence already exists for a number of agents to be so considered, and definitive confirmation seems imminent due to the application ofrecently developed genomic techniques. In preparatio...

  4. Reduction of hexavalent chromium by fasted and fed human gastric fluid. I. Chemical reduction and mitigation of mutagenicity.

    PubMed

    De Flora, Silvio; Camoirano, Anna; Micale, Rosanna T; La Maestra, Sebastiano; Savarino, Vincenzo; Zentilin, Patrizia; Marabotto, Elisa; Suh, Mina; Proctor, Deborah M

    2016-09-01

    Evaluation of the reducing capacity of human gastric fluid from healthy individuals, under fasted and fed conditions, is critical for assessing the cancer hazard posed by ingested hexavalent chromium [Cr(VI)] and for developing quantitative physiologically-based pharmacokinetic models used in risk assessment. In the present study, the patterns of Cr(VI) reduction were evaluated in 16 paired pre- and post-meal gastric fluid samples collected from 8 healthy volunteers. Human gastric fluid was effective both in reducing Cr(VI), as measured by using the s-diphenylcarbazide colorimetric method, and in attenuating mutagenicity in the Ames test. The mean (±SE) Cr(VI)-reducing ability of post-meal samples (20.4±2.6μgCr(VI)/mL gastric fluid) was significantly higher than that of pre-meal samples (10.2±2.3μgCr(VI)/mL gastric fluid). When using the mutagenicity assay, the decrease of mutagenicity produced by pre-meal and post-meal samples corresponded to reduction of 13.3±1.9 and 25.6±2.8μgCr(VI)/mL gastric fluid, respectively. These data are comparable to parallel results conducted by using speciated isotope dilution mass spectrometry. Cr(VI) reduction was rapid, with >70% of total reduction occurring within 1min and 98% of reduction is achieved within 30min with post-meal gastric fluid at pH2.0. pH dependence was observed with decreasing Cr(VI) reducing capacity at higher pH. Attenuation of the mutagenic response is consistent with the lack of DNA damage observed in the gastrointestinal tract of rodents following administration of ≤180ppm Cr(VI) for up to 90days in drinking water. Quantifying Cr(VI) reduction kinetics in the human gastrointestinal tract is necessary for assessing the potential hazards posed by Cr(VI) in drinking water. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. INVESTIGATING THE SOURCES OF THE MUTAGENIC ACTIVITY FOUND IN A RIVER USING THE SALMONELLA ASSAY AND DIFFERENT WATER EXTRACTION PROCEDURES

    EPA Science Inventory

    Abstract
    As a consequence of the routine surface water quality-monitoring program of Sao Paulo State (Brazil), which includes the Salmonella microsome mutagenicity assay as one of its parameters, we detected a river used as a drinking water source after treatment, that repeate...

  6. Mutagenicity and Pollutant Emission Factors of Solid-Fuel Cookstoves: Comparison with Other Combustion Sources

    PubMed Central

    Mutlu, Esra; Warren, Sarah H.; Ebersviller, Seth M.; Kooter, Ingeborg M.; Schmid, Judith E.; Dye, Janice A.; Linak, William P.; Gilmour, M. Ian; Jetter, James J.; Higuchi, Mark; DeMarini, David M.

    2016-01-01

    Background: Emissions from solid fuels used for cooking cause ~4 million premature deaths per year. Advanced solid-fuel cookstoves are a potential solution, but they should be assessed by appropriate performance indicators, including biological effects. Objective: We evaluated two categories of solid-fuel cookstoves for eight pollutant and four mutagenicity emission factors, correlated the mutagenicity emission factors, and compared them to those of other combustion emissions. Methods: We burned red oak in a 3-stone fire (TSF), a natural-draft stove (NDS), and a forced-draft stove (FDS), and we combusted propane as a liquified petroleum gas control fuel. We determined emission factors based on useful energy (megajoules delivered, MJd) for carbon monoxide, nitrogen oxides (NOx), black carbon, methane, total hydrocarbons, 32 polycyclic aromatic hydrocarbons, PM2.5, levoglucosan (a wood-smoke marker), and mutagenicity in Salmonella. Results: With the exception of NOx, the emission factors per MJd were highly correlated (r ≥ 0.97); the correlation for NOx with the other emission factors was 0.58–0.76. Excluding NOx, the NDS and FDS reduced the emission factors an average of 68 and 92%, respectively, relative to the TSF. Nevertheless, the mutagenicity emission factor based on fuel energy used (MJthermal) for the most efficient stove (FDS) was between those of a large diesel bus engine and a small diesel generator. Conclusions: Both mutagenicity and pollutant emission factors may be informative for characterizing cookstove performance. However, mutagenicity emission factors may be especially useful for characterizing potential health effects and should be evaluated in relation to health outcomes in future research. An FDS operated as intended by the manufacturer is safer than a TSF, but without adequate ventilation, it will still result in poor indoor air quality. Citation: Mutlu E, Warren SH, Ebersviller SM, Kooter IM, Schmid JE, Dye JA, Linak WP, Gilmour MI, Jetter

  7. RESIDUAL MUTAGENICITY OF THE ALASKAN OIL SPILL ORGANICS

    EPA Science Inventory

    RESIDUAL MUTAGENICITY OF THE ALASKAN OIL SPILL ORGANICS. L.D.

    The Exxon Valdez, on March 24, 1989, spilled approximately eleven million gallons of Prudhoe Bay crude oil into the waters of Prince William Sound. Approximately 300 miles of
    contaminated beach are potential...

  8. Evaluation of Antitrypanosomal Dihydroquinolines for Hepatotoxicity, Mutagenicity, and Methemoglobin Formation In Vitro.

    PubMed

    Werbovetz, Karl A; Riccio, Edward S; Furimsky, Anna; Richard, Julian V; He, Shanshan; Iyer, Lalitha; Mirsalis, Jon

    2014-07-01

    N1-Benzylated dihydroquinolin-6-ols and their corresponding esters display exceptional activity against African trypanosomes in vitro, and administration of members of this class of compounds to trypanosome-infected mice results in cures in a first-stage African trypanosomiasis model. Since a quinone imine intermediate has been implicated in the antiparasitic mechanism of action of these compounds, evaluation of the hepatotoxic, mutagenic, and methemoglobin-promoting effects of these agents was performed. 1-Benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-ol hydrochloride and 1-benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate showed outstanding in vitro selectivity for Trypanosoma brucei compared to the HepG2, Hep3B, Huh7, and PLC5 hepatocyte cell lines. 1-Benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-ol hydrochloride and 1-(2-methoxybenzyl)-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate were not mutagenic when screened in the Ames assay, with or without metabolic activation. The latter 2 compounds promoted time- and dose-dependent formation of methemoglobin when incubated in whole human blood, but such levels were below those typically required to produce symptoms of methemoglobinemia in humans. Although compounds capable of quinone imine formation require careful evaluation, these in vitro studies indicate that antitrypanosomal dihydroquinolines merit further study as drug candidates against the neglected tropical disease human African trypanosomiasis. © The Author(s) 2014.

  9. Toxicity, uptake, and mutagenicity of particulate and soluble nickel compounds.

    PubMed Central

    Fletcher, G G; Rossetto, F E; Turnbull, J D; Nieboer, E

    1994-01-01

    Toxicity testing in AS52 cells (24-hr exposures) gave LC50 values of 2 to 130 micrograms Ni/ml for particulate nickel compounds and 45 to 60 micrograms Ni/ml for water-soluble salts (NiCl2, NiSO4, Ni(CH3COO)2). The Ni(OH)2, NiCO3, and sulfides (Ni3S2, Ni7S6, "amorphous NiS") exhibited similar toxicities (LC50's of 2 to 8 micrograms Ni/ml), while three nickel oxides were more variable and less toxic (LC50's of 18 to 130 micrograms Ni/ml). Most compounds displayed nuclear to cytoplasmic nickel ratios of approximately 1:1.5 to 1:5 (except approximately 1:20 for nickel salts). At the LC50's, a 75-fold range in exposure levels occurred compared to a 10-fold range in cytoplasmic and nuclear nickel concentrations, [Ni]. Cellular nickel distribution indicated three groupings: inert compounds (green NiO, lithium nickel oxide, relatively low nuclear and cytosolic [Ni]); water-soluble salts (very low nuclear [Ni]; high cytosolic [Ni]), and slightly soluble compounds (relatively high cytosolic and nuclear [Ni]). Nickel compounds are considered to be only weak or equivocal mutagens. In this study, a low but significant increase in mutation rate at the gpt locus was shown. Although the results would not be sufficient to deem nickel compounds mutagenic by traditional criteria, characterization by PCR analysis indicated that the spontaneous and nickel-induced mutants exhibited different and compound-specific mutational spectra (thus confirming nickel compound involvement). The results reported illustrate some of the methodologic problems involved in testing "weak" mutagens and indicate that alternative approaches may be necessary in classifying the mutagenicity of nickel and other compounds. PMID:7843140

  10. Fruit extract of the medicinal plant Crataegus oxyacantha exerts genotoxic and mutagenic effects in cultured cells.

    PubMed

    de Quadros, Ana Paula Oliveira; Mazzeo, Dania Elisa Christofoletti; Marin-Morales, Maria Aparecida; Perazzo, Fábio Ferreira; Rosa, Paulo Cesar Pires; Maistro, Edson Luis

    2017-01-01

    Crataegus oxyacantha, a plant of the Rosaceae family also known "English hawthorn, haw, maybush, or whitethorn," has long been used for medicinal purposes such as digestive disorders, hyperlipidemia, dyspnea, inducing diuresis, and preventing kidney stones. However, the predominant use of this plant has been to treat cardiovascular disorders. Due to a lack of studies on the genotoxicity of C. oxyacantha, this investigation was undertaken to determine whether its fruit extract exerts cytotoxic, genotoxic, or clastogenic/aneugenic effects in leukocytes and HepG2 (liver hepatocellular carcinoma) cultured human cells, or mutagenic effects in TA100 and TA98 strains of Salmonella typhimurium bacterium. Genotoxicity analysis showed that the extract produced no marked genotoxic effects at concentrations of 2.5 or 5 µg/ml in either cell type; however, at concentrations of 10 µg/ml or higher significant DNA damage was detected. The micronucleus test also demonstrated that concentrations of 10 µg/ml or higher produced clastogenic/aneugenic responses. In the Ames test, the extract induced mutagenic effects in TA98 strain of S. typhimurium with metabolic activation at all tested concentrations (2.5 to 500 µg/ml). Data indicate that, under certain experimental conditions, the fruit extract of C. oxyacantha exerts genotoxic and clastogenic/aneugenic effects in cultured human cells, and with metabolism mutagenicity occurs in bacteria cells.

  11. USE OF BIOASSAY-DIRECTED CHEMICAL ANALYSIS FOR IDENTIFYING MUTAGENIC COMPOUNDS IN URBAN AIR AND COMBUSTION EMISSIONS

    EPA Science Inventory

    Bioassay-directed chemical analysis fractionation has been used for 30 years to identify mutagenic classes of compounds in complex mixtures. Most studies have used the Salmonella (Ames) mutagenicity assay, and we have recently applied this methodology to two standard reference sa...

  12. Attesting the efficiency of monitored natural attenuation in the detoxification of sewage sludge by means of genotoxic and mutagenic bioassays.

    PubMed

    Mazzeo, Dânia Elisa Christofoletti; Fernandes, Thaís Cristina Casimiro; Marin-Morales, Maria Aparecida

    2016-11-01

    A viable alternative to the use of sewage sludge (SS) would be using it as a reconditioner of agricultural soils, due to its high content of organic matter and nutrients. However, this solution may contaminate the soil, since SS may contain toxic substances. Monitored natural attenuation is a process that can be used in the decontamination of SS before its disposal into the environment. The effectiveness of the natural attenuation of a domestic SS was evaluated over 12 months by assays of Salmonella/microsome and micronucleus (MN) in human hepatoma cells (HepG2). Mutagenic activity was observed for the Salmonella strain TA 100, with S9, for the extracts from periods 0-6 months of natural attenuation. Genotoxic effects were observed in HepG2 cells, for 0 and 2 months, in almost all tested concentrations. Comparing obtained data by MN test to chemical analyses, it is possible to observe a coincidence between the induction of MN and the quantity of the m- and p-cresol, since these compounds were present in the initial SS and after 2 months of natural attenuation, decreasing their concentrations in samples from 6 to 12 months. The positive results obtained with Salmonella/microsome (from 6 months) suggest a combined action of other substances in SS. These results indicated that this SS, in the earlier periods tested, is potentially genotoxic and mutagenic and that its disposal can lead to severe environmental problems. Thus, the use of the studied SS as reconditioner requires pre-processing for over than 6 months of natural attenuation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Epistatic Interactions within the Influenza A Virus Polymerase Complex Mediate Mutagen Resistance and Replication Fidelity

    PubMed Central

    Pauly, Matthew D.; Lyons, Daniel M.; Fitzsimmons, William J.

    2017-01-01

    ABSTRACT Lethal mutagenesis is a broad-spectrum antiviral strategy that employs mutagenic nucleoside analogs to exploit the high mutation rate and low mutational tolerance of many RNA viruses. Studies of mutagen-resistant viruses have identified determinants of replicative fidelity and the importance of mutation rate to viral population dynamics. We have previously demonstrated the effective lethal mutagenesis of influenza A virus using three nucleoside analogs as well as the virus’s high genetic barrier to mutagen resistance. Here, we investigate the mutagen-resistant phenotypes of mutations that were enriched in drug-treated populations. We find that PB1 T123A has higher replicative fitness than the wild type, PR8, and maintains its level of genome production during 5-fluorouracil (2,4-dihydroxy-5-fluoropyrimidine) treatment. Surprisingly, this mutagen-resistant variant also has an increased baseline rate of C-to-U and G-to-A mutations. A second drug-selected mutation, PA T97I, interacts epistatically with PB1 T123A to mediate high-level mutagen resistance, predominantly by limiting the inhibitory effect of nucleosides on polymerase activity. Consistent with the importance of epistatic interactions in the influenza virus polymerase, our data suggest that nucleoside analog resistance and replication fidelity are strain dependent. Two previously identified ribavirin {1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-1,2,4-triazole-3-carboxamide} resistance mutations, PB1 V43I and PB1 D27N, do not confer drug resistance in the PR8 background, and the PR8-PB1 V43I polymerase exhibits a normal baseline mutation rate. Our results highlight the genetic complexity of the influenza A virus polymerase and demonstrate that increased replicative capacity is a mechanism by which an RNA virus can counter the negative effects of elevated mutation rates. IMPORTANCE RNA viruses exist as genetically diverse populations. This standing genetic diversity gives them

  14. Analyses of the genotoxic and mutagenic potential of the products formed after the biotransformation of the azo dye Disperse Red 1.

    PubMed

    Chequer, Farah Maria Drumond; Lizier, Thiago Mescoloto; de Felício, Rafael; Zanoni, Maria Valnice Boldrin; Debonsi, Hosana Maria; Lopes, Norberto Peporine; Marcos, Ricard; de Oliveira, Danielle Palma

    2011-12-01

    Azo dyes constitute the largest class of synthetic dyes. Following oral exposure, these dyes can be reduced to aromatic amines by the intestinal microflora or liver enzymes. This work identified the products formed after oxidation and reduction of the dye Disperse Red 1, simulating hepatic biotransformation and evaluated the mutagenic potential of the resultant solution. Controlled potential electrolysis was carried out on dye solution using a Potentiostat/Galvanostat. HPLC-DAD and GC/MS were used to determine the products generated after the oxidation/reduction process. The Salmonella/microsome assay with the strains TA98 and YG1041 without S9, and the mouse lymphoma assay (MLA) using the thymidine kinase (Tk) gene, were used to evaluate the mutagenicity of the products formed. Sulfate 2-[(4-aminophenyl)ethylamino]-ethanol monohydrate, nitrobenzene, 4-nitro-benzamine and 2-(ethylphenylamino)-ethanol were detected. This dye has already being assigned as mutagenic in different cell system. In addition, after the oxidation/reduction process the dye still had mutagenic activity for the Salmonella/microsome assay. Nevertheless, both the original dye Disperse Red 1 and its treated solutions showed negative results in the MLA. The present results suggest that the ingestion of water and food contaminated with this dye may represent human and environmental health problem, due to the generation of harmful compounds after biotransformation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Using "Saccharomyces cerevisiae" to Test the Mutagenicity of Household Compounds: An Open Ended Hypothesis-Driven Teaching Lab

    ERIC Educational Resources Information Center

    Marshall, Pamela A.

    2007-01-01

    In our Fundamentals of Genetics lab, students perform a wide variety of labs to reinforce and extend the topics covered in lecture. I developed an active-learning lab to augment the lecture topic of mutagenesis. In this lab exercise, students determine if a compound they bring from home is a mutagen. Students are required to read extensive…

  16. An Evaluation of the Mode of Action Framework for MutagenicCarcinogens Case Study II: Chromium (VI).

    EPA Science Inventory

    In response to the 2005 revised U.S Environmental Protection Agency’s (EPA) Cancer Guidelines, a strategy is being developed to include all mutagenicity and other genotoxicity data with any additional information to determine whether a carcinogen operates through a mutagenic mode...

  17. Mutagenicity of Diesel and Soy Biodiesel Exhaust Particles

    EPA Science Inventory

    Mutagenicity Of Diesel And Soy Biodiesel Exhaust Particles E Mutlua,b' SH Warrenb, PP Matthewsb, CJ Kingb, B Prestonc, MD Haysb, DG Nashb,ct, WP Linakb, MI Gilmourb, and DM DeMarinib aUniversity of North Carolina, Chapel Hill, NC bU.S. Environmental Agency, Research Triangle Pa...

  18. Mutagenicity and genotoxicity of coal fly ash water leachate

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chakraborty, R.; Mukherjee, A.

    2009-03-15

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

  19. Template properties of mutagenic cytosine analogues in reverse transcription

    PubMed Central

    Suzuki, Tetsuya; Moriyama, Kei; Otsuka, Chie; Loakes, David; Negishi, Kazuo

    2006-01-01

    We have studied the mutagenic properties of ribonucleotide analogues by reverse transcription to understand their potential as antiretroviral agents by mutagenesis of the viral genome. The templating properties of nucleotide analogues including 6-(β-D-ribofuranosyl)-3,4-dihydro-8H-pyrimido[4,5-c](1,2)oxazin-7-one, N4-hydroxycytidine, N4-methoxycytidine, N4-methylcytidine and 4-semicarbazidocytidine, which have been reported to exhibit ambiguous base pairing properties, were examined. We have synthesized RNA templates using T3 RNA polymerase, and investigated the specificity of the incorporation of deoxyribonucleoside triphosphates opposite these cytidine analogues in RNA by HIV and AMV reverse transcriptases. Except for N4-methylcytidine, both enzymes incorporated both dAMP and dGMP opposite these analogues in RNA. This indicates that they would be highly mutagenic if present in viral RNA. To study the basis of the differences among the analogues in the incorporation ratios of dAMP to dGMP, we have carried out kinetic analysis of incorporation opposite the analogues at a defined position in RNA templates. In addition, we examined whether the triphosphates of these analogues were incorporated competitively into RNA by human RNA polymerase II. Our present data supports the view that these cytidine analogues are mutagenic when incorporated into RNA, and that they may therefore be considered as candidates for antiviral agents by causing mutations to the retroviral genome. PMID:17130163

  20. Mutagens and carcinogens in foods. Epidemiologic review.

    PubMed Central

    Hislop, T. G.

    1993-01-01

    Evidence that diet contributes to the development of cancer is strengthening. This paper examines mutagens and carcinogens, such as naturally occurring substances, products of cooking and food processing, intentional and unintentional additives, and contaminants, found in foods. Such substances are present in minute quantities in the diets of average Canadians. Indication of health risk is largely limited to experimental laboratory evidence. PMID:8499796

  1. Cytotoxic, phytotoxic, and mutagenic appraisal to ascertain toxicological potential of particulate matter emitted from automobiles.

    PubMed

    Anwar, Khaleeq; Ejaz, Sohail; Ashraf, Muhammad; Altaf, Imran; Anjum, Aftab Ahmad

    2013-07-01

    Vehicular air pollution is a mounting health issue of the modern age, particularly in urban populations of the developing nations. Auto-rickshaws are not considered eco-friendly as to their inefficient engines producing large amount of particulate matter (PM), thus posing significant environmental threat. The present study was conducted to ascertain the cytotoxic, phytotoxic, and mutagenic potential of PM from gasoline-powered two-stroke auto-rickshaws (TSA) and compressed natural gas-powered four-stroke auto-rickshaws (FSA). Based on the increased amount of aluminum quantified during proton-induced X-ray emission analysis of PM from TSA and FSA, different concentrations of aluminum sulfate were also tested to determine its eco-toxicological potential. The MTT assay demonstrated significant (p < 0.001) dose-dependent cytotoxic effects of different concentrations of TSA, FSA, and aluminum sulfate on BHK-21 cell line. LC50 of TSA, FSA, and aluminum sulfate was quantified at 16, 11, and 23.8 μg/ml, respectively, establishing PM from FSA, a highly cytotoxic material. In case of phytotoxicity screening using Zea mays, the results demonstrated that all three tested materials were equally phytotoxic at higher concentrations producing significant reduction (p < 0.001) in seed germination. Aluminum sulfate proved to be a highly phytotoxic agent even at its lowest concentration. Mutagenicity was assessed by fluctuation Salmonella reverse mutation assay adopting TA100 and TA98 mutant strains with (+S9) and without (-S9) metabolic activation. Despite the fact that different concentrations of PM from both sources, i.e., TSA and FSA were highly mutagenic (p < 0.001) even at lower concentrations, the mutagenic index was higher in TSA. Data advocate that all tested materials are equally ecotoxic, and if the existing trend of atmospheric pollution by auto-rickshaws is continued, airborne heavy metals will seriously affect the normal growth of local inhabitants and

  2. A perspective of Genes and Environment for the development of environmental mutagen research in Asia.

    PubMed

    Yagi, Takashi

    2017-01-01

    Two years have passed since the Japanese Environmental Society (JEMS) made the official journal Genes and Environment (G&E) open access. Current subjects on environmental mutagen research to further advance this field are described herein, and the roles of JEMS and G&E are discussed. Various important subjects are being investigated in current research fields such as severe environmental pollution in Asian countries; the identification of new hazardous substances and elucidation of mutation mechanisms using newly developed techniques; the development of new genotoxicity assays including in silico predictions using information technology and artificial intelligence as well as bioassays. International exchange by scientists is important for advancing these research fields through international conferences such as the 12th International Conference and 5th Asian Congress on Environmental Mutagens and the 7th International Workshop on Genotoxicity Testing that will be held in 2017. G&E provides a common platform for high quality environmental mutagen research, contributes to the dissemination of Asian environmental mutagen research, and potentiates the level of research being conducted.

  3. Antigenotoxic effects of Citrus aurentium L. fruit peel oil on mutagenicity of two alkylating agents and two metals in the Drosophila wing spot test.

    PubMed

    Demir, Eşref; Kocaoğlu, Serap; Cetin, Huseyin; Kaya, Bülent

    2009-07-01

    Antigenotoxic effects of Citrus aurentium L. (Rutaceae) fruit peel oil (CPO) in combination with mutagenic metals and alkylating agents were studied using the wing spot test of D. melanogaster. The four reference mutagens, potassium dichromate (K2Cr2O7), cobalt chloride (CoCl2), ethylmethanesulfonate (EMS), and N-ethyl-N-nitrosourea (ENU) were clearly genotoxic. CPO alone at doses from 0.1 to 0.5% in Tween 80 was not mutagenic and did not enhance the mutagenic effect of the reference mutagens. However, antigenotoxic effects of CPO were clearly demonstrated in chronic cotreatments with mutagens and oil, by a significant decrease in wing spots induced by all four mutagens. The D. melanogaster wing spot test was found to be a suitable assay for detecting antigenotoxic effects in vivo. Copyright 2009 Wiley-Liss, Inc.

  4. Mutagenicity studies of urine and faecal samples from rats treated orally with the food colourings Brown FK and Red 2G.

    PubMed

    Edwards, C N; Combes, R D

    1984-08-01

    Urine and faecal extracts from rats given Brown FK or Red 2G orally (800 mg/kg body weight) were investigated for mutagenicity. Extracts were subjected to liquid fluctuation and plate incorporation assays with Salmonella typhimurium strains TA98 and TA100 in the presence and absence of liver microsomes and/or a beta-glucuronidase-sulphatase preparation. Urine from Red 2G-treated rats only exhibited direct activity when coloured fractions from polyamide-column concentrates were tested with TA100. All other urines, as well as aqueous and ether faecal extracts from animals receiving either colouring, were no more mutagenic than the respective control extracts obtained from the same animals prior to dosing.

  5. Mutagenicity and polycyclic aromatic hydrocarbons associated with extractable organic matter from airborne particles ⩽10 μm in southwest Mexico City

    NASA Astrophysics Data System (ADS)

    Villalobos-Pietrini, Rafael; Amador-Muñoz, Omar; Waliszewski, Stefan; Hernández-Mena, Leonel; Munive-Colín, Zenaida; Gómez-Arroyo, Sandra; Bravo-Cabrera, José Luis; Frías-Villegas, Alejandro

    A year-long sampling and analysis of 24 h airborne particles equal to or less than 10 μm (PM 10) was conducted in Southwest (SW) Mexico City in 1998. The amount of airborne PM 10 and its extractable organic matter (EOM) were highly correlated. The year 1998 was particularly dry with many fires, and higher values of PM 10 and EOM were obtained in the fire period (February-May) compared to the without fire period (January, June-December). The indirect-acting mutagenicity ( Salmonella typhimurium strain TA98 with mammalian metabolic activation, S9) did not correlate with the monthly concentrations of PM 10 and EOM, while the direct-acting mutagenicity (strains TA98 and YG1021, without mammalian metabolic activation) did correlate. The highest monthly mutagenic potency of TA98+S9 and of TA98-S9 were registered in May which correspond to the fire period, while for YG1021 the highest was in December, a without fire month. The highest TA98+S9/TA98-S9 ratios appeared from April to September (with the exception of June), indicating that emission of the direct mutagens occurred in the rest of the year (the coldest months), and December showed the highest mutagenicity of YG1021. The correlation of this mutagenicity with the number of ground-based inversions indicated a greater emissions of nitroarenes in the coldest months emitted mainly by vehicular traffic as shown by the correlation between YG1021 with CO and with NO 2. We did not find a correlation in the EOM of the complex mixtures between TA98+S9 and the total concentration of polycyclic aromatic hydrocarbons (PAH) nor between TA98+S9 and specific PAH. The analysis by gas chromatography/mass spectrometry indicated the presence of retene, a PAH found in the fire period and considered a softwood burning marker. The concentrations of fluoranthene and benz[ a]anthracene correlated with that of retene and with the burned area; they were the only PAH that presented significant differences between the periods with fire and

  6. Long-term effects of inducible mutagenic DNA repair on relative fitness and phenotypic diversification in Pseudomonas cichorii 302959.

    PubMed

    Weigand, Michael R; Sundin, George W

    2009-01-01

    Mutagenic DNA repair (MDR) employs low-fidelity DNA polymerases capable of replicating past DNA lesions resulting from exposure to high-energy ultraviolet radiation (UVR). MDR confers UVR tolerance and activation initiates a transient mutator phenotype that may provide opportunities for adaptation. To investigate the potential role of MDR in adaptation, we have propagated parallel lineages of the highly mutable epiphytic plant pathogen Pseudomonas cichorii 302959 with daily UVR activation (UVR lineages) for approximately 500 generations. Here we examine those lineages through the measurement of relative fitness and observation of distinct colony morphotypes that emerged. Isolates and population samples from UVR lineages displayed gains in fitness relative to the ancestor despite increased rates of inducible mutation to rifampicin resistance. Regular activation of MDR resulted in the maintenance of genetic diversity within UVR lineages, including the reproducible diversification and coexistence of "round" and "fuzzy" colony morphotypes. These results suggest that inducible mutability may present a reasonable strategy for adaptive evolution in stressful environments by contributing to gains in relative fitness and diversification.

  7. Estimation of mutagenic effect and modifications of mitosis by silver nanoparticles.

    PubMed

    Prokhorova, I M; Kibrik, B S; Pavlov, A V; Pesnya, D S

    2013-12-01

    We analyzed mutagenic and mitosis-modifying effects of silver nanoparticles (Allium test). Chromosome aberrations and laggings and micronuclei were simultaneously registered in the same sample. Mitotic and phase indexes were calculated. No mutagenic effects were detected after treatment with silver nanoparticles in doses of 1.0, 2.5, 5.0, and 50 mg/liter. Silver nanoparticles in a concentration of 50 mg/liter significantly increased the mitotic index. Nanoparticles in a dose of 5 mg/liter induced slight, but significant increase in mitotic index, but did not affect the ratio of phase indexes. Exposure to silver nanoparticles in concentrations of 1.0 and 2.5 mg/liter was not followed by modification of mitosis.

  8. THE CASE FOR THE CONTRIBUTION OF CRISTAIS RIVER NITRO-AMINOBENZENE DYES TO THE MUTAGENICITY OF AMBIENT SAMPLES

    EPA Science Inventory

    In order to verify if dyestuffs within an effluent of a textile industry was contributing to the systematic mutagenicity detected in the Cristais River, within the metropolitan region of Sao Paulo, mutagenic samples of the industrial effluent, crude water, and treated silt of the...

  9. Biological activity of particle exhaust emissions from light-duty diesel engines.

    PubMed

    Carraro, E; Locatelli, A L; Ferrero, C; Fea, E; Gilli, G

    1997-01-01

    Whole diesel exhaust has been classified recently as a probable carcinogen, and several genotoxicity studies have found particulate exhaust to be clearly mutagenic. Moreover, genotoxicity of diesel particulate is greatly influenced by fuel nature and type of combustion. In order to obtain an effective environmental pollution control, combustion processes using alternative fuels are being analyzed presently. The goal of this study is to determine whether the installation of exhaust after treatment-devices on two light-duty, exhaust gas recirculation (EGR) valve-equipped diesel engines (1930 cc and 2500 cc) can reduce the mutagenicity associated with particles collected during U.S.A. and European driving cycles. Another interesting object was to compare the ability of alternative biodiesel and conventional diesel fuels to reduce the mutagenic activity associated with collected particles from two light duty diesel engines (both 1930 cc) during the European driving cycle. SOF mutagenicity was assayed using the Salmonella/microsome test (TA 98 and TA 100 strains, +/- S9 fraction). In the first part of our study, the highest mutagenicity was revealed by TA98 strain without enzymatic activation, suggesting a direct-acting mutagenicity prevalence in diesel particulate. The 2500 cc engine revealed twofold mutagenic activity compared with the 1930 cc engine (both EGR valve equipped), whereas an opposite result was found in particulate matter amount. The use of a noncatalytic ceramic trap produced a decrease of particle mutagenic activity in the 2500 cc car, whereas an enhancement in the 1930 cc engine was found. The catalytic converter and the electrostatic filter installed on the 2500 cc engine yielded a light particle amount and an SOF mutagenicity decrease. A greater engine stress was obtained using European driving cycles, which caused the strongest mutagenicity/km compared with the U.S.A. cycles. In the second part of the investigation, even though a small number of

  10. THE SOURCES, FATE AND HAZARDS OF MUTAGENS IN SURFACE WATERS

    EPA Science Inventory

    A variety of industrial, domestic and agricultural wastes are discharged into rivers, lakes, streams, and estuaries. In some instances, these wastes contain substances that are capable I of permanently altering the genetic material of exposed organisms (i.e., they are mutagens). ...

  11. Miscoding and mutagenic properties of 8-oxoguanine and abasic sites: Ubiquitous lesions in damaged DNA

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Grollman, A.P.; Takeshita, Masaru

    1995-12-31

    More than twenty oxidatively-damaged bases, including 8-oxoguanine, have been found to occur in genomic DNA. Some of these lesions block DNA replication and are potentially lethal; others generate mutations which can initiate carcinogenesis and promote cellular aging. In this report, the authors focus attention on the mutagenicity and repair of 8-oxoguanine. Kasai and Nishimura`s discovery that hydroxyl radicals react with guanine residues in DNA to form 8-oxoguanine and the development of sensitive methods for the detection and quantitation of this modified base led to the observation that approximately 1 in 10{sup 5} guanine residues in mammalian DNA are oxidized atmore » the C-8 position. DNA containing 8-oxoguanine and synthetic analogs of the abasic site have been used to investigate the miscoding and mutagenic potential of these ubiquitous lesions. Studies in the laboratory were facilitated by the development of solid state synthetic methods by which these lesions could be introduced at defined positions in DNA. In this paper, the authors review studies in which 8-oxoguanine and abasic sites have been used in model systems to explore various early events in the replication of selectively damaged DNA.« less

  12. Different responses of vanillic acid, a phenolic compound, in HTC cells: cytotoxicity, antiproliferative activity, and protection from DNA-induced damage.

    PubMed

    Almeida, I V; Cavalcante, F M L; Vicentini, V E P

    2016-12-19

    The consumption of healthy and natural foods has increased over the last few years, primarily because these foods are rich in substances with biological properties of interest, such as exerting anticancer effects and decreasing oxidative stress in living tissues. These foods support adequate nutrition, maintain health, and improve quality of life. Vanillic acid (VA) is a phenolic compound used widely in the food industry as a flavoring, preservative, and food additive. VA can be found in various cereals, whole grains, fruits, herbs, green tea, juices, beers, and wines and possesses antioxidant, hepatoprotective, cardioprotective, and antiapoptotic activities. Studying the cytotoxicity as well as the mutagenic and antimutagenic effects of different concentrations of VA in Rattus norvegicus hepatoma cells (HTC) can identify new cellular activities of this substance. Concentrations up to 100 µM VA are not cytotoxic to HTC cells in a MTT [3-(4,5-dimethilthiazol-2-yl)-2,5-diphenil tetrazolium bromide] assay after 96-h exposure; therefore, VA does not compromise mitochondrial activity. Similarly, concentrations up to 500 µM do not compromise plasma membrane integrity. VA at 10 and 50 µM showed no mutagenic/clastogenic effects, as no significant micronuclei induction was observed. VA 10 µM presented no antiproliferative activity and reduced the cytotoxicity induced by benzo[a]pyrene. The antimutagenic activity of 10 µM VA was observed by the simultaneous, pre-, and post-treatments, as the phenolic compound significantly reduced the frequency of micronuclei induced by the mutagen. These results indicate that VA exerts different responses in HTC cells. Low concentrations present no cytotoxic, mutagenic, or antiproliferative effects and protect cells from DNA damage.

  13. Mutagenicity of the Musa paradisiaca (Musaceae) fruit peel extract in mouse peripheral blood cells in vivo.

    PubMed

    Andrade, C U B; Perazzo, F F; Maistro, E L

    2008-01-01

    Plants are a source of many biologically active products and nowadays they are of great interest to the pharmaceutical industry. In the present study, the mutagenic potential of the Musa paradisiaca fruit peel extract was assessed by the single-cell gel electrophoresis (SCGE) and micronucleus assays. Animals were treated orally with three different concentrations of the extract (1000, 1500, and 2000 mg/kg body weight). Peripheral blood cells of Swiss mice were collected 24 h after treatment for the SCGE assay and 48 and 72 h for the micronucleus test. The results showed that the two higher doses of the extract of M. paradisiaca induced statistically significant increases in the average numbers of DNA damage in peripheral blood leukocytes for the two higher doses and a significant increase in the mean of micronucleated polychromatic erythrocytes in the three doses tested. The polychromatic/normochromatic erythrocyte ratio scored in the treated groups was not statistically different from the negative control. The data obtained indicate that fruit peel extract from M. paradisiaca showed mutagenic effect in the peripheral blood cells of Swiss albino mice.

  14. IN VITRO AND IN VIVO MUTAGENICITY STUDIES OF ENVIRONMENTAL CHEMICALS

    EPA Science Inventory

    The objectives of this project were to evaluate the mutagenicity of various compounds, mostly pesticides, using microbial and mammalian cell in vitro techniques, as well as in vivo techniques in Drosophila and mice, and to further develop and refine these procedures for applicati...

  15. The Concentrations but Not the Components of Particulate Material and Secondary Transformation Products May Account for Much of the Variation in Air Mutagenicity

    EPA Science Inventory

    The mutagenic potency of ambient air PM in the Salmonella mutagenicity assay (rev/mg PM) varies only ~1 order of magnitude worldwide; however, the mutagenic potency of the air itself (rev/m3 of air) varies ~5 orders of magnitude (IARC Monograph Vol 109, 2016). Thus, the componen...

  16. Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish.

    PubMed

    Sugimura, Takashi; Wakabayashi, Keiji; Nakagama, Hitoshi; Nagao, Minako

    2004-04-01

    Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public

  17. A novel QSAR model of Salmonella mutagenicity and its application in the safety assessment of drug impurities

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Valencia, Antoni; Prous, Josep; Mora, Oscar

    As indicated in ICH M7 draft guidance, in silico predictive tools including statistically-based QSARs and expert analysis may be used as a computational assessment for bacterial mutagenicity for the qualification of impurities in pharmaceuticals. To address this need, we developed and validated a QSAR model to predict Salmonella t. mutagenicity (Ames assay outcome) of pharmaceutical impurities using Prous Institute's Symmetry℠, a new in silico solution for drug discovery and toxicity screening, and the Mold2 molecular descriptor package (FDA/NCTR). Data was sourced from public benchmark databases with known Ames assay mutagenicity outcomes for 7300 chemicals (57% mutagens). Of these data, 90%more » was used to train the model and the remaining 10% was set aside as a holdout set for validation. The model's applicability to drug impurities was tested using a FDA/CDER database of 951 structures, of which 94% were found within the model's applicability domain. The predictive performance of the model is acceptable for supporting regulatory decision-making with 84 ± 1% sensitivity, 81 ± 1% specificity, 83 ± 1% concordance and 79 ± 1% negative predictivity based on internal cross-validation, while the holdout dataset yielded 83% sensitivity, 77% specificity, 80% concordance and 78% negative predictivity. Given the importance of having confidence in negative predictions, an additional external validation of the model was also carried out, using marketed drugs known to be Ames-negative, and obtained 98% coverage and 81% specificity. Additionally, Ames mutagenicity data from FDA/CFSAN was used to create another data set of 1535 chemicals for external validation of the model, yielding 98% coverage, 73% sensitivity, 86% specificity, 81% concordance and 84% negative predictivity. - Highlights: • A new in silico QSAR model to predict Ames mutagenicity is described. • The model is extensively validated with chemicals from the FDA and the public domain. • Validation

  18. Mutagenicity of drinking water sampled from the Yangtze River and Hanshui River (Wuhan section) and correlations with water quality parameters.

    PubMed

    Lv, Xuemin; Lu, Yi; Yang, Xiaoming; Dong, Xiaorong; Ma, Kunpeng; Xiao, Sanhua; Wang, Yazhou; Tang, Fei

    2015-03-31

    A total of 54 water samples were collected during three different hydrologic periods (level period, wet period, and dry period) from Plant A and Plant B (a source for Yangtze River and Hanshui River water, respectively), and several water parameters, such as chemical oxygen demand (COD), turbidity, and total organic carbon (TOC), were simultaneously analyzed. The mutagenicity of the water samples was evaluated using the Ames test with Salmonella typhimurium strains TA98 and TA100. According to the results, the organic compounds in the water were largely frame-shift mutagens, as positive results were found for most of the tests using TA98. All of the finished water samples exhibited stronger mutagenicity than the relative raw and distribution water samples, with water samples collected from Plant B presenting stronger mutagenic strength than those from Plant A. The finished water samples from Plant A displayed a seasonal-dependent variation. Water parameters including COD (r = 0.599, P = 0.009), TOC (r = 0.681, P = 0.02), UV254 (r = 0.711, P = 0.001), and total nitrogen (r = 0.570, P = 0.014) exhibited good correlations with mutagenicity (TA98), at 2.0 L/plate, which bolsters the argument of the importance of using mutagenicity as a new parameter to assess the quality of drinking water.

  19. Mutagenicity of drinking water sampled from the Yangtze River and Hanshui River (Wuhan section) and correlations with water quality parameters

    PubMed Central

    Lv, Xuemin; Lu, Yi; Yang, Xiaoming; Dong, Xiaorong; Ma, Kunpeng; Xiao, Sanhua; Wang, Yazhou; Tang, Fei

    2015-01-01

    A total of 54 water samples were collected during three different hydrologic periods (level period, wet period, and dry period) from Plant A and Plant B (a source for Yangtze River and Hanshui River water, respectively), and several water parameters, such as chemical oxygen demand (COD), turbidity, and total organic carbon (TOC), were simultaneously analyzed. The mutagenicity of the water samples was evaluated using the Ames test with Salmonella typhimurium strains TA98 and TA100. According to the results, the organic compounds in the water were largely frame-shift mutagens, as positive results were found for most of the tests using TA98. All of the finished water samples exhibited stronger mutagenicity than the relative raw and distribution water samples, with water samples collected from Plant B presenting stronger mutagenic strength than those from Plant A. The finished water samples from Plant A displayed a seasonal-dependent variation. Water parameters including COD (r = 0.599, P = 0.009), TOC (r = 0.681, P = 0.02), UV254 (r = 0.711, P = 0.001), and total nitrogen (r = 0.570, P = 0.014) exhibited good correlations with mutagenicity (TA98), at 2.0 L/plate, which bolsters the argument of the importance of using mutagenicity as a new parameter to assess the quality of drinking water. PMID:25825837

  20. Mutagenic cost of ribonucleotides in bacterial DNA

    PubMed Central

    Schroeder, Jeremy W.; Randall, Justin R.; Hirst, William G.; O’Donnell, Michael E.; Simmons, Lyle A.

    2017-01-01

    Replicative DNA polymerases misincorporate ribonucleoside triphosphates (rNTPs) into DNA approximately once every 2,000 base pairs synthesized. Ribonucleotide excision repair (RER) removes ribonucleoside monophosphates (rNMPs) from genomic DNA, replacing the error with the appropriate deoxyribonucleoside triphosphate (dNTP). Ribonucleotides represent a major threat to genome integrity with the potential to cause strand breaks. Furthermore, it has been shown in the bacterium Bacillus subtilis that loss of RER increases spontaneous mutagenesis. Despite the high rNTP error rate and the effect on genome integrity, the mechanism underlying mutagenesis in RER-deficient bacterial cells remains unknown. We performed mutation accumulation lines and genome-wide mutational profiling of B. subtilis lacking RNase HII, the enzyme that incises at single rNMP residues initiating RER. We show that loss of RER in B. subtilis causes strand- and sequence-context–dependent GC → AT transitions. Using purified proteins, we show that the replicative polymerase DnaE is mutagenic within the sequence context identified in RER-deficient cells. We also found that DnaE does not perform strand displacement synthesis. Given the use of nucleotide excision repair (NER) as a backup pathway for RER in RNase HII-deficient cells and the known mutagenic profile of DnaE, we propose that misincorporated ribonucleotides are removed by NER followed by error-prone resynthesis with DnaE. PMID:29078353

  1. Evaluating the mutagenic potential of aerosol organic compounds using informatics-based screening

    NASA Astrophysics Data System (ADS)

    Decesari, Stefano; Kovarich, Simona; Pavan, Manuela; Bassan, Arianna; Ciacci, Andrea; Topping, David

    2018-02-01

    Whilst general policy objectives to reduce airborne particulate matter (PM) health effects are to reduce exposure to PM as a whole, emerging evidence suggests that more detailed metrics associating impacts with different aerosol components might be needed. Since it is impossible to conduct toxicological screening on all possible molecular species expected to occur in aerosol, in this study we perform a proof-of-concept evaluation on the information retrieved from in silico toxicological predictions, in which a subset (N = 104) of secondary organic aerosol (SOA) compounds were screened for their mutagenicity potential. An extensive database search showed that experimental data are available for 13 % of the compounds, while reliable predictions were obtained for 82 %. A multivariate statistical analysis of the compounds based on their physico-chemical, structural, and mechanistic properties showed that 80 % of the compounds predicted as mutagenic were grouped into six clusters, three of which (five-membered lactones from monoterpene oxidation, oxygenated multifunctional compounds from substituted benzene oxidation, and hydroperoxides from several precursors) represent new candidate groups of compounds for future toxicological screenings. These results demonstrate that coupling model-generated compositions to in silico toxicological screening might enable more comprehensive exploration of the mutagenic potential of specific SOA components.

  2. MUTAGENICITY OF NITRITE-TREATED AQUEOUS EXTRACT OF 'PIPER BETLE'; L

    EPA Science Inventory

    Betel quid is chewed as a masticatory material by people in certain areas of Asia. The quid chewing has been related to oral cancer by epidemiological study. The mutagenic components in the aqueous extracts of betel quid ingredients were studied. Only nitrite-treated aqueous extr...

  3. MUTAGENICITY AND CARCINOGENICITY ASSESSMENT OF 1,3-BUTADIENE. REVIEW DRAFT

    EPA Science Inventory

    The Mutagenicity and Carcinogenicity Assessment of 1,3-Butadiene was prepared to serve as a source document for Agency-wide use. In the development of this assessment document, the scientific literature has been inventoried, key studies have been evaluated, and the summary and co...

  4. Examination of in vivo mutagenicity of sodium arsenite and dimethylarsinic acid in gpt delta rats.

    PubMed

    Fujioka, Masaki; Gi, Min; Kawachi, Satoko; Tatsumi, Kumiko; Ishii, Naomi; Doi, Kenichiro; Kakehashi, Anna; Wanibuchi, Hideki

    2016-11-01

    Arsenic is a well-known human bladder and liver carcinogen, but its exact mechanism of carcinogenicity is not fully understood. Dimethylarsinic acid (DMA V ) is a major urinary metabolite of sodium arsenite (iAs III ) and induces urinary bladder cancers in rats. DMA V and iAs III are negative in in vitro mutagenicity tests. However, their in vivo mutagenicities have not been determined. The purpose of present study is to evaluate the in vivo mutagenicities of DMA V and iAs III in rat urinary bladder epithelium and liver using gpt delta F344 rats. Ten-week old male gpt delta F344 rats were randomized into 3 groups and administered 0, 92mg/L DMA V , or 87mg/L iAs III (each 50mg/L As) for 13weeks in the drinking water. In the mutation assay, point mutations are detected in the gpt gene by 6-thioguanine selection (gpt assay) and deletion mutations are identified in the red/gam genes by Spi - selection (Spi - assay). Results of the gpt and Spi - assays showed that DMA V and iAs III had no effects on the mutant frequencies or mutation spectrum in urinary bladder epithelium or liver. These findings indicate that DMA V and iAs III are not mutagenic in urinary bladder epithelium or liver in rats. Copyright © 2016. Published by Elsevier B.V.

  5. Chemopreventive effect and lack of genotoxicity and mutagenicity of the exopolysaccharide botryosphaeran on human lymphocytes.

    PubMed

    Malini, M; Camargo, M S; Hernandes, L C; Vargas-Rechia, C G; Varanda, E A; Barbosa, A M; Dekker, R F H; Matsumoto, S T; Antunes, L M G; Cólus, I M S

    2016-10-01

    Carbohydrate biopolymers of fungal-origin are an important natural resource in the search for new bioagents with therapeutic and nutraceutical potential. In this study the mutagenic, genotoxic, antigenotoxic and antioxidant properties of the fungal exopolysaccharide botryosphaeran, a (1→3)(1→6)-β-D-glucan, from Botryosphaeria rhodina MAMB-05, was evaluated. The mutagenicity was assessed at five concentrations in Salmonella typhimurium by the Ames test. Normal and tumor (Jurkat cells) human T lymphocyte cultures were used to evaluate the genotoxicity and antigenotoxicity (Comet assay) of botryosphaeran alone and in combination with the mutagen methyl methanesulfonate (MMS). The ability of botryosphaeran to reduce the production of reactive oxygen and nitrogen species (RONS) generated by hydrogen peroxide was assessed using the CM-H2DCFDA probe in lymphocyte cultures under different treatment times. None of the evaluated botryosphaeran concentrations were mutagenic in bacteria, nor induced genotoxicity in normal and tumor lymphocytes. Botryosphaeran protected lymphocyte DNA against damage caused by MMS under simultaneous treatment and post-treatment conditions. However, botryosphaeran was not able to reduce the RONS generated by H2O2. Besides the absence of genotoxicity, botryosphaeran exerted a protective effect on human lymphocytes against genotoxic damage caused by MMS. These results are important in the validation of botryosphaeran as a therapeutic agent targeting health promotion. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. In vitro mutagenicity assessment of aluminium oxide nanomaterials using the Salmonella/microsome assay.

    PubMed

    Balasubramanyam, A; Sailaja, N; Mahboob, M; Rahman, M F; Hussain, Saber M; Grover, Paramjit

    2010-09-01

    The aim of the current study was to evaluate the potential mutagenicity of aluminium oxide nanomaterials (NMs) (Al(2)O(3)-30 nm and Al(2)O(3)-40 nm). Characterization of the NMs was done before the initiation of the study. The mutagenicity of the NMs was studied by the Ames test with Salmonella typhimurium TA100, TA1535, TA98, TA97a and TA102 strains, in the presence and absence of the S9 mixture. Based on a preliminary cytotoxicity study conducted on the strains, different concentrations of Al(2)O(3)-30 nm, Al(2)O(3)-40 nm and Al(2)O(3)-bulk were selected. At all the concentrations tested, Al(2)O(3)-30 nm and Al(2)O(3)-40 nm did not significantly increase the number of revertant colonies compared to the Al(2)O(3)-bulk and control with or without S9 mixture. Our findings suggest that Al(2)O(3) NMs were devoid of any size and concentration dependent mutagenicity compared to the Al(2)O(3)-bulk and control. Copyright 2010 Elsevier Ltd. All rights reserved.

  7. Removals of pesticides and pesticide transformation products during drinking water treatment processes and their impact on mutagen formation potential after chlorination.

    PubMed

    Matsushita, Taku; Morimoto, Ayako; Kuriyama, Taisuke; Matsumoto, Eisuke; Matsui, Yoshihiko; Shirasaki, Nobutaka; Kondo, Takashi; Takanashi, Hirokazu; Kameya, Takashi

    2018-07-01

    Removal efficiencies of 28 pesticide transformation products (TPs) and 15 parent pesticides during steps in drinking water treatment (coagulation-sedimentation, activated carbon adsorption, and ozonation) were estimated via laboratory-scale batch experiments, and the mechanisms underlying the removal at each step were elucidated via regression analyses. The removal via powdered activated carbon (PAC) treatment was correlated positively with the log K ow at pH 7. The adjusted coefficient of determination (r 2 ) increased when the energy level of the highest occupied molecular orbital (HOMO) was added as an explanatory variable, the suggestion being that adsorption onto PAC particles was largely governed by hydrophobic interactions. The residual error could be partly explained by π-π electron donor-acceptor interactions between the graphene surface of the PAC particles and the adsorbates. The removal via ozonation correlated positively with the energy level of the HOMO, probably because compounds with relatively high energy level HOMOs could more easily transfer an electron to the lowest unoccupied molecular orbital of ozone. Overall, the TPs tended to be more difficult to remove via PAC adsorption and ozonation than their parent pesticides. However, the TPs that were difficult to remove via PAC adsorption did not induce strong mutagenicity after chlorination, and the TPs that were associated with strong mutagenicity after chlorination could be removed via PAC adsorption. Therefore, PAC adsorption is hypothesized to be an effective method of treating drinking water to reduce the possibility of post-chlorination mutagenicity associated with both TPs and their parent pesticides. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Antioxidative and antimutagenic activities of healthy herbal drinks from Chinese medicinal herbs.

    PubMed

    Chen, Wenlung; Weng, Yih-Ming; Tseng, Chin-Yin

    2003-01-01

    Twenty-nine Chinese medicinal herbs and three healthy herbal drinks made of those herbs in a food processing pilot plant were tested for their antioxidative, free radical scavenging, mutagenic and antimutagenic activities. Water extracts of herbs (with few exceptions) and herbal drinks showed free radical scavenging activity. All water extracts of herbs and herbal drinks showed no mutagenicity toward Salmonella typhimurium tester strains TA98 and TA100 used in the Ames mutagenic tests. In the antimutagenic tests, the mutagenic activity of 4-nitroquinoline N-oxide (NQNO) toward S. typhimurium TA98 was markedly inhibited by water extracts of herbs and herbal drinks. Based on the results, it is suggested that the herbal drinks manufactured in pilot-plant scale are safe and can be served as health-promoting drinks for the public.

  9. Mutagenicity and antimutagenicity of Baccharis dracunculifolia extract in chromosomal aberration assays in Chinese hamster ovary cells.

    PubMed

    Munari, Carla Carolina; Resende, Flávia Aparecida; Alves, Jacqueline Morais; de Sousa, João Paulo; Bastos, Jairo Kenupp; Tavares, Denise Crispim

    2008-09-01

    Baccharis dracunculifolia De Candole (Asteraceae), a native plant from the Brazilian "cerrado", is widely used in folk medicine as an anti-inflammatory agent and for the treatment of gastrointestinal diseases. B. dracunculifolia has been described as the most important plant source of propolis in southeastern Brazil, which is called green propolis due to its color. The aim of the present study was to evaluate the mutagenic and antimutagenic effects of the ethyl acetate extract of B. dracunculifolia leaves (Bd-EAE) on Chinese hamster ovary cells. On one hand, the results showed a significant increase in the frequencies of chromosome aberrations at the highest Bd-EAE concentration tested (100 microg/mL). On the other hand, the lowest Bd-EAE concentration tested (12.5 micro/mL) significantly reduced the chromosome damage induced by the chemotherapeutic agent doxorubicin. The present results indicate that Bd-EAE has the characteristics of a so-called Janus compound, that is, Bd-EAE is mutagenic at higher concentrations, whereas it displays a chemopreventive effect on doxorubicin-induced mutagenicity at lower concentrations. The constituents of B. dracunculifolia responsible for its mutagenic and antimutagenic effects are probably flavonoids and phenylpropanoids, since these compounds can act either as pro-oxidants or as free radical scavengers depending on their concentration.

  10. Mutagenicity testing with transgenic mice. Part I: Comparison with the mouse bone marrow micronucleus test

    PubMed Central

    Wahnschaffe, U; Bitsch, A; Kielhorn, J; Mangelsdorf, I

    2005-01-01

    As part of a larger literature study on transgenic animals in mutagenicity testing, test results from the transgenic mutagenicity assays (lacI model; commercially available as the Big Blue® mouse, and the lacZ model; commercially available as the Muta™Mouse), were compared with the results on the same substances in the more traditional mouse bone marrow micronucleus test. 39 substances were found which had been tested in the micronucleus assay and in the above transgenic mouse systems. Although, the transgenic animal mutation assay is not directly comparable with the micronucleus test, because different genetic endpoints are examined: chromosome aberration versus gene mutation, the results for the majority of substances were in agreement. Both test systems, the transgenic mouse assay and the mouse bone marrow micronucleus test, have advantages and they complement each other. However, the transgenic animal assay has some distinct advantages over the micronucleus test: it is not restricted to one target organ and detects systemic as well as local mutagenic effects. PMID:15655069

  11. Azo dyes in clothing textiles can be cleaved into a series of mutagenic aromatic amines which are not regulated yet.

    PubMed

    Brüschweiler, Beat J; Merlot, Cédric

    2017-08-01

    Azo dyes represent the by far most important class of textile dyes. Their biotransformation by various skin bacteria may release aromatic amines (AAs) which might be dermally absorbed to a major extent. Certain AAs are well known to have genotoxic and/or carcinogenic properties. Correspondingly, azo dyes releasing one of the 22 known carcinogenic AAs are banned from clothing textiles in the European Union. In the present study, we investigated the mutagenicity of 397 non-regulated AAs potentially released from the 470 known textile azo dyes. We identified 36 mutagenic AAs via publicly available databases. After predicting their mutagenicity potential using the method by Bentzien, we accordingly allocated them into different priority groups. Ames tests on 18 AAs of high priority showed that 4 substances (22%) (CASRN 84-67-3, 615-47-4, 3282-99-3, 15791-87-4) are mutagenic in the strain TA98 and/or TA100 with and/or without rat S9 mix. Overall, combining the information from the Ames tests and the publicly available data, we identified 40 mutagenic AAs being potential cleavage products of approximately 180 different parent azo dyes comprising 38% of the azo dyes in our database. The outcome of this study indicates that mutagenic AAs in textile azo dyes are of much higher concern than previously expected, which entails implications on the product design and possibly on the regulation of azo dyes in the future. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Cytotoxicity But No Mutagenicity In Bacteria With Externally Generated Singlet Oxygen

    NASA Astrophysics Data System (ADS)

    Midden, W. Robert; Dahl, Thomas A.; Hartman, Philip E.

    1988-02-01

    Singlet oxygen is believed to be an important intermediate responsible for the cytotoxicity of HpD phototherapy. It has been recognized as a possible intermediate in photosensitization for more than 20 years. However, it has been difficult to obtain conclusive evidence of its biological characteristics in the past because most of the methods available for its generation that are compatible with biological systems also generate other reactive intermediates whose effects are difficult to distinguish from singlet oxygen. We have used a recently devised separated-surface-sensi-tizer (S-S-S) system for singlet oxygen generation' to measure the cytotoxicity and mutagenicity of singlet oxygen in bacteria. The S-S-S system employs rose bengal as a sensitizer immobilized on one surface of a glass plate. The glass plate is placed sensitizer-side down a small distance (< 1.5 mm) above a microscopically flat membrane (MilliporeTM or NucleoporeTM) that carries a monocellular layer of bacteria. The sensi-tizer-coated plate is illuminated from above to generate singlet oxygen at the surface of the sensitizer. The singlet oxygen thus generated can diffuse the short dis-tance to the surface of the membrane to react with the bacteria. Because of the short lifetime of singlet oxygen in air, increasing the distance between the sensitizer and the membrane causes a decline in the amount of singlet oxygen reaching the membrane according to a function derived from the Einstein-Smoluchowski equation for net displacement by diffusion. Plotting the log of the effect measured (e.g., cytotoxicity) vs. the square of the distance gives a straight line. The slope of this line can be used to calculate the gas phase half life of the intermediate responsible for the observed effects. We have found that bacteria are rapidly killed in the illuminated S-S-S system and that the gas phase half life of the agent responsible for cell killing is the same as that of singlet oxygen. This observation and other

  13. Quantitative mammalian cell genetic toxicology: study of the cytotoxicity and mutagenicity of 70 individual environmental agents related to energy technologies and 3 subfractions of a crude synthetic oil in the CHO/HGPRT system. [Hamsters

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hsie, A W; ,; Neill, J P

    1978-01-01

    Conditions necessary for quantifying mutation-induction to 6-thioguanine resistance, which selects for >98% mutants deficient in the activity of hypoxanthine-guanine phosphoribosyl transferase (HGPRT) in a near-diploid Chinese hamster ovary (CHO) cell line, referred to as CHO/HGPRT system, have been defined. Employing this mutation assay, we have determined the mutagenicity of diversified agents including 11 direct-acting alkylating agents, 16 nitrosamines, 10 heterocyclic nitrogen mustards, 15 metallic compounds, 5 quinolines, 5 aromatic amines, 27 polycyclic hydrocarbons, 13 miscellaneous chemicals, 7 ionizing and non-ionizing physical agents. The direct-acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine is mutagenic while its noncarcinogenic analogue N-methyl-N'-nitro-N-nitroguanidine is not. Coupled with the rat livermore » S/sub 9/-activation system, procarcinogens such as nitrosopyrrolidine, benzo(a)pyrene, and 2-acetylaminofluorene are mutagenic while their analogues 2,5-dimethylnitrosopyrrolidine, pyrene and fluorene are not. The assay appears to be applicable for monitoring the genetic toxicity of crude organic mixtures in addition to diverse individual chemical and physical agents. The quantitative nature of the assay enables a study of EMS exposure dose: the mutagenic potential of EMS can be described as 310 x 10/sup -6/ mutants (cell mg ml/sup -1/ h)./sup -1/ It is also feasible to expand the CHO/HGPRT system for quantifying cytotoxicity and mutagenicity to determination of chromosomal aberrations and sister chromatid exchanges in cells treated under identical conditions which allows a simultaneous study of these four distinctive biological effects.« less

  14. Heptyl prodigiosin, a bacterial metabolite, is antimalarial in vivo and non-mutagenic in vitro.

    PubMed

    Lazaro, J Enrico H; Nitcheu, Josiane; Predicala, Rey Z; Mangalindan, Gina C; Nesslany, Fabrice; Marzin, Daniel; Concepcion, Gisela P; Diquet, Bertrand

    2002-12-01

    Heptyl prodigiosin was purified from a culture of alpha-proteobacteria isolated from a marine tunicate collected in Zamboanga, Philippines, as part of a program to screen natural products for antiparasitic activity. An in vitro antimalarial activity similar to that of quinine was found against the chloroquine-sensitive strain Plasmodium falciparum 3D7. The in vitro antimalarial activity was about 20 times the in vitro cytotoxic activity against L5178Y mouse lymphocytes. A single subcutaneous administration of 5 and 20 mg/kg significantly extended survival of P. berghei ANKA strain-infected mice but also caused sclerotic lesions at the site of injection. A single administration by gavage of 50 mg/kg did not increase survival time. The compound was not found to be mutagenic using in vitro micromethods for the Ames Salmonella typhimurium assay and the micronucleus assay using L5178Y mouse lymphoma cells.

  15. GENERAL ENHANCEMENT OF MUTAGENIC POTENCY OF VARIOUS MUTAGENS DUE TO DELETED GENES IN THE ΔuvrB STRAINS TA 98 AND TA 100 OF SALMONELLA COMPARED WITH STRAINS CONTAINING ONLY A POINT MUTATION IN uvrB

    EPA Science Inventory

    The two most common strains used in Ames mutagenicity assays, TA98 and TA 100, contain a �uvrB mutation designed to enhance the mutagenicity of compounds, presumably due to the loss of the nucleotide excision repair system. We showed previously that the �uvrB mutations in these s...

  16. The Small RNA GcvB Promotes Mutagenic Break Repair by Opposing the Membrane Stress Response

    PubMed Central

    Barreto, Brittany; Rogers, Elizabeth; Xia, Jun; Frisch, Ryan L.; Richters, Megan; Fitzgerald, Devon M.

    2016-01-01

    ABSTRACT Microbes and human cells possess mechanisms of mutagenesis activated by stress responses. Stress-inducible mutagenesis mechanisms may provide important models for mutagenesis that drives host-pathogen interactions, antibiotic resistance, and possibly much of evolution generally. In Escherichia coli, repair of DNA double-strand breaks is switched to a mutagenic mode, using error-prone DNA polymerases, via the SOS DNA damage and general (σS) stress responses. We investigated small RNA (sRNA) clients of Hfq, an RNA chaperone that promotes mutagenic break repair (MBR), and found that GcvB promotes MBR by allowing a robust σS response, achieved via opposing the membrane stress (σE) response. Cells that lack gcvB were MBR deficient and displayed reduced σS-dependent transcription but not reduced σS protein levels. The defects in MBR and σS-dependent transcription in ΔgcvB cells were alleviated by artificially increasing σS levels, implying that GcvB promotes mutagenesis by allowing a normal σS response. ΔgcvB cells were highly induced for the σE response, and blocking σE response induction restored both mutagenesis and σS-promoted transcription. We suggest that GcvB may promote the σS response and mutagenesis indirectly, by promoting membrane integrity, which keeps σE levels lower. At high levels, σE might outcompete σS for binding RNA polymerase and so reduce the σS response and mutagenesis. The data show the delicate balance of stress response modulation of mutagenesis. IMPORTANCE Mutagenesis mechanisms upregulated by stress responses promote de novo antibiotic resistance and cross-resistance in bacteria, antifungal drug resistance in yeasts, and genome instability in cancer cells under hypoxic stress. This paper describes the role of a small RNA (sRNA) in promoting a stress-inducible-mutagenesis mechanism, mutagenic DNA break repair in Escherichia coli. The roles of many sRNAs in E. coli remain unknown. This study shows that ΔgcvB cells

  17. The Small RNA GcvB Promotes Mutagenic Break Repair by Opposing the Membrane Stress Response.

    PubMed

    Barreto, Brittany; Rogers, Elizabeth; Xia, Jun; Frisch, Ryan L; Richters, Megan; Fitzgerald, Devon M; Rosenberg, Susan M

    2016-12-15

    Microbes and human cells possess mechanisms of mutagenesis activated by stress responses. Stress-inducible mutagenesis mechanisms may provide important models for mutagenesis that drives host-pathogen interactions, antibiotic resistance, and possibly much of evolution generally. In Escherichia coli, repair of DNA double-strand breaks is switched to a mutagenic mode, using error-prone DNA polymerases, via the SOS DNA damage and general (σ S ) stress responses. We investigated small RNA (sRNA) clients of Hfq, an RNA chaperone that promotes mutagenic break repair (MBR), and found that GcvB promotes MBR by allowing a robust σ S response, achieved via opposing the membrane stress (σ E ) response. Cells that lack gcvB were MBR deficient and displayed reduced σ S -dependent transcription but not reduced σ S protein levels. The defects in MBR and σ S -dependent transcription in ΔgcvB cells were alleviated by artificially increasing σ S levels, implying that GcvB promotes mutagenesis by allowing a normal σ S response. ΔgcvB cells were highly induced for the σ E response, and blocking σ E response induction restored both mutagenesis and σ S -promoted transcription. We suggest that GcvB may promote the σ S response and mutagenesis indirectly, by promoting membrane integrity, which keeps σ E levels lower. At high levels, σ E might outcompete σ S for binding RNA polymerase and so reduce the σ S response and mutagenesis. The data show the delicate balance of stress response modulation of mutagenesis. Mutagenesis mechanisms upregulated by stress responses promote de novo antibiotic resistance and cross-resistance in bacteria, antifungal drug resistance in yeasts, and genome instability in cancer cells under hypoxic stress. This paper describes the role of a small RNA (sRNA) in promoting a stress-inducible-mutagenesis mechanism, mutagenic DNA break repair in Escherichia coli The roles of many sRNAs in E. coli remain unknown. This study shows that ΔgcvB cells

  18. Intakes of red meat, processed meat, and meat-mutagens increase lung cancer risk

    PubMed Central

    Lam, Tram Kim; Cross, Amanda J.; Consonni, Dario; Randi, Giorgia; Bagnardi, Vincenzo; Bertazzi, Pier Alberto; Caporaso, Neil E.; Sinha, Rashmi; Subar, Amy F.; Landi, Maria Teresa

    2009-01-01

    Red and processed meat intake may increase lung cancer risk. However, the epidemiologic evidence is inconsistent and few studies have evaluated the role of meat-mutagens formed during high cooking temperatures. We investigated the association of red meat, processed meat, and meat-mutagen intake with lung cancer risk in Environment And Genetics in Lung cancer Etiology (EAGLE), a population-based case-control study. Primary lung cancer cases (n=2101) were recruited from 13 hospitals within the Lombardy region of Italy examining ~80% of the cases from the area. Non-cancer population controls (n=2120), matched to cases on gender, residence, and age, were randomly selected from the same catchment area. Diet was assessed in 1903 cases and 2073 controls, and used in conjunction with a meat-mutagen database to estimate intake of heterocyclic amines and benzo[a]pyrene. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) for sex-specific tertiles of intake were calculated using unconditional logistic regression. Red and processed meat were positively associated with lung cancer risk (highest-versus-lowest tertile: OR=1.8; 95% CI=1.5–2.2; p-trend<0.001 and OR=1.7; 95% CI=1.4–2.1; p-trend<0.001, respectively); the risks were strongest among never smokers (OR=2.4, 95% CI=1.4–4.0, p-trend=0.001 and OR=2.5, 95% CI=1.5–4.2, p-trend=0.001, respectively). Heterocyclic amines and benzo[a]pyrene were significantly associated with increased risk of lung cancer. When separated by histology, significant positive associations for both meat groups were restricted to adenocarcinoma and squamous cell carcinoma, but not small cell carcinoma of the lung. In summary, red meat, processed meat, and meat-mutagens were independently associated with increased risk of lung cancer. PMID:19141639

  19. Dietary Intake of Meat Cooking-Related Mutagens (HCAs) and Risk of Colorectal Adenoma and Cancer: A Systematic Review and Meta-Analysis

    PubMed Central

    Chiavarini, Manuela; Bertarelli, Gaia; Minelli, Liliana; Fabiani, Roberto

    2017-01-01

    Much evidence suggests that the positive association between meat intake and colorectal adenoma (CRA) and cancer (CRC) risk is mediated by mutagenic compounds generated during cooking at high temperature. A number of epidemiological studies have estimated the effect of meat-related mutagens intake on CRC/CRA risk with contradictory and sometimes inconsistent results. A literature search was carried out (PubMed, Web of Science and Scopus) to identify articles reporting the relationship between the intake of meat-related mutagens (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline: DiMeIQx, benzo(a) pyrene (B(a)P) and “meat derived mutagenic activity” (MDM)) and CRC/CRA risk. A random-effect model was used to calculate the risk association. Thirty-nine studies were included in the systematic review and meta-analysis. Polled CRA risk (15229 cases) was significantly increased by intake of PhIP (OR = 1.20; 95% CI: 1.13,1.28; p < 0.001), MeIQx (OR = 1.14; 95% CI: 1.05,1.23; p = 0.001), DiMeIQx (OR = 1.13; 95% CI: 1.05,1.21; p = 0.001), B(a)P (OR = 1.10; 95% CI: 1.02,1.19; p = 0.017) and MDM (OR = 1.17; 95% CI: 1.07,1.28; p = 0.001). A linear and curvilinear trend was observed in dose–response meta-analysis between CRA risk in association with PhIP, MDM, and MeIQx. CRC risk (21,344 cases) was increased by uptake of MeIQx (OR = 1.14; 95% CI: 1.04,1.25; p = 0.004), DiMeIQx (OR = 1.12; 95% CI: 1.02,1.22; p = 0.014) and MDM (OR = 1.12; 95% CI: 1.06,1.19; p < 0.001). No publication bias could be detected, whereas heterogeneity was in some cases rather high. Mutagenic compounds formed during cooking of meat at high temperature may be responsible of its carcinogenicity. PMID:28524104

  20. Peptide bond-forming reagents HOAt and HATU are not mutagenic in the bacterial reverse mutation test.

    PubMed

    Nicolette, John; Neft, Robin E; Vanosdol, Jessica; Murray, Joel

    2016-04-01

    The peptide bond-forming reagents 1-hydroxy-7-azabenzotriazole (HOAt, CAS 39968-33-7) and O-(7-Azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU, CAS 148893-10-1) either have structural alerts, unclassified features or are considered out of domain when evaluated for potential mutagenicity with in silico programs DEREK and CaseUltra. Since they are commonly used reagents in pharmaceutical drug syntheses, they may become drug substance or drug product impurities and would need to be either controlled to appropriately safe levels or tested for mutagenicity. Both reagents were tested in the bacterial reverse mutation (Ames) test at Covance, under GLP conditions, following the OECD test guideline and ICH S2(R1) recommendations and found to be negative. Our data show that HOAt and HATU-common pharmaceutical synthesis reagents-are not mutagenic, and can be treated as ordinary drug impurities. © 2016 Wiley Periodicals, Inc.

  1. A REVIEW OF THE RODENT CARCINOGENICTY AND MUTAGENICITY OF AMBIENT AIR

    EPA Science Inventory

    This is a review of the information known about the carcinogenicity and mutagenicity of urban outdoor air including volatile pollutants and particulate organic material. The editors of Mutation Research decided to create a second special review volume on what is known about ...

  2. Health Effects of Soy-Biodiesel Emissions: Bioassay-Directed Fractionation for Mutagenicity*

    EPA Science Inventory

    BACKGROUND:Soy biodiesel is the predominant biodiesel used in the U.S., but there is little understanding of the classes of chemicals responsible for the mutagenicity of the emissions.OBJECTIVE: We determined some of the chemical classes responsible for various categories of mut...

  3. Diesel emissions significantly influence composition and mutagenicity of ambient particles: a case study in São Paulo, Brazil.

    PubMed

    Carvalho-Oliveira, R; Pozo, R M K; Lobo, D J A; Lichtenfels, A J F C; Martins-Junior, H A; Bustilho, J O W V; Saiki, M; Sato, I M; Saldiva, P H N

    2005-05-01

    In 2003, a bus strike paralyzed the fleet of buses in Sao Paulo, Brazil during 3 days, from 6 to 8 of April, the complete interruption of services being achieved on the 7th. We evaluated the effect of the absence of this source of pollution on the composition, mutagenicity, and toxicity of the fine particulate material collected during this period. Particles were sampled in glass fiber filters on days 7 and 15 of April of 2003 (strike and nonstrike days, respectively), using a high-volume sampler. Trace element determinations (As, Br, Co, Cl, Fe, La, Mn, Sb, Sc, and Th) of particulate material samples were carried out by neutron activation analysis. Sulfur determination was done by X-ray fluorescence analysis. The ratio between nonstrike/strike concentrations of hydrocarbons associated with automotive emissions (benzene, toluene, ethyl-benzene, and xylenes; BTEX) was determined by gas chromatography/mass spectrometry. Mutagenesis of testing solutions was determined by means of the Tradescantia micronucleus assay in early tetrads of Tradescantia pallida. The inhibition of mitosis of the cells of the primary meristema of the root tips of Allium cepa was used as an index of the toxicity. Fine particle trace element contents were lower during the strike. The concentrations of sulfur and BTEX were 50% and 39.3% lower, respectively, on the strike day. A significant (P=0.038) reduction of micronuclei induced by fine particles sampled during the strike was observed. No effect of the strike on toxicity was detected. These results indicate that a program aiming to reduce emissions of the bus fleet in our town may impact positively the air quality by reducing the mutagenic potential of ambient particles.

  4. Genotoxic activity of 4,4',5'-trimethylazapsoralen on plasmid DNA.

    PubMed

    Lagatolla, C; Dolzani, L; Granzotto, M; Monti-Bragadin, C

    1998-01-01

    The genotoxic activities of 8-methoxypsoralen (8-MOP) and 4,4',5'-trimethylazapsoralen (4,4',5'-TMAP) on plasmid DNA have been compared. In a previous work, 4,4',5'-TMAP, a methyl derivative of a psoralen isoster, had shown potential photochemotherapeutic activity. The mutagenic activity of mono- and bifunctional lesions caused by these compounds was evaluated both after UVA irradiation, which causes the formation of both kinds of lesions, and after a two-step irradiation procedure of the psoralen-plasmid DNA complex, which allowed monoadducts and interstrand crosslinks to be studied separately. Furthermore, we used a procedure that allowed us to evaluate both the mutagenic and recombinogenic activity of the two compounds. Results indicate that the most important difference between 8-MOP and 4,4',5'-TMAP consists in their mode of photoreaction with DNA rather than in their mutagenic potential. In fact, in all of the experimental procedures, 4,4',5'-TMAP shows a lower ability than 8-MOP to generate interstrand crosslinks. However, when comparable toxicity levels are reached, the two compounds show the same mutagenic potentiality.

  5. Reproductive Effects Assessment Group's Report on the Mutagenicity of Inorganic Arsenic

    EPA Science Inventory

    Various inorganic compounds of arsenic have been tested for mutagenicity in a variety of test systems ranging in complexity from bacteria to peripheral lymphocytes of exposed human beings. Although a great deal of the data are contradictory, the weight of evidence supports the fo...

  6. In vitro evaluation of the mutagenic and carcinogenic power of high purity zirconia ceramic.

    PubMed

    Covacci, V; Bruzzese, N; Maccauro, G; Andreassi, C; Ricci, G A; Piconi, C; Marmo, E; Burger, W; Cittadini, A

    1999-02-01

    Tetragonal zirconia polycrystal (TZP) is a new interesting ceramic for the manufacture of medical devices. Its wide use in orthopedic and odontoiatric implants was limited till now by the high chemical and radiochemical impurities of the raw materials. Purification processes now available allow to obtain high purity ceramic grade powders suitable for TZP ceramics manufacture, even if their possible mutagenic and transforming effects are still unclear. The aim of this work is to study in vitro the mutagenic and oncogenic effects of a new zirconia ceramic stabilized by yttria (Y-TZP). This ceramic was sintered from high purity powders obtained by a process developed under a project carried out within the Brite EuRam programme. For comparison, ceramics made from unpurified zirconia powder were also tested. Fibroblasts irradiated by a linear accelerator were used as positive control. The results obtained show that Y-TZP ceramic does not elicit either mutagenic or transforming effect on C3H/10T(1/2) (10T(1/2)) cells and demonstrate that ceramic from high purity powders can be considered suitable for biomedical applications from the point of view of the effects of its radioactive impurity content.

  7. Toxicity, mutagenicity and transport in Saccharomyces cerevisiae of three popular DNA intercalating fluorescent dyes.

    PubMed

    Sayas, Enric; García-López, Federico; Serrano, Ramón

    2015-09-01

    We have compared the toxicity, mutagenicity and transport in Saccharomyces cerevisiae of three DNA-intercalating fluorescent dyes widely used to stain DNA in gels. Safety data about ethidium bromide (EtBr) are contradictory, and two compounds of undisclosed structure (Redsafe and Gelred) have been proposed as safe alternatives. Our results indicate that all three compounds inhibit yeast growth, with Gelred being the most inhibitory and also the only one causing cell death. EtBr and Gelred, but not Redsafe, induce massive formation of petite (non-respiratory) mutants, but only EtBr induces massive loss of mitochondrial DNA. All three compounds increase reversion of a chromosomal point mutation (lys2-801(amber) ), with Gelred being the most mutagenic and Redsafe the least. These dyes are all cationic and are probably taken by cells through non-selective cation channels. We could measure the glucose-energized transport of EtBr and Gelred inside the cells, while uptake of Redsafe was below our detection limit. We conclude that although all three compounds are toxic and mutagenic in the yeast system, Redsafe is the safest for yeast, probably because of very limited uptake by these cells. Copyright © 2015 John Wiley & Sons, Ltd.

  8. Identification of polycyclic aromatic hydrocarbons in mutagenic adsorbates to a copper-phthalocyanine derivative recovered from municipal river water.

    PubMed

    Sayato, Y; Nakamuro, K; Ueno, H; Goto, R

    1993-08-01

    A study was made to identify polycyclic aromatic hydrocarbons (PAHs) in the mutagenic adsorbate to blue cotton recovered from the water of the Katsura River which is a tributary of the Yodo River, a typical municipal river. As blue cotton bears a covalently bound copper-phthalocyanine derivative which can adsorb PAHs over 3 rings, PAHs in the adsorbate were separated into 4 fractions (I-IV) by Sephadex LH-20 gel chromatography. Fractions III and IV showed high direct and indirect frameshift mutagenicity in strains YG1021 and YG1024, the nitroreductase- and O-acetyltransferase-overproducing derivatives of TA98, especially in YG1024 with S9 mix, whereas these fractions showed less mutagenicity in TA98NR or TA98/1,8-DNP6. These results suggest that mutagenic nitroarenes and aminoarenes are present in both fractions. The retention times of some peaks separated from both fractions using high performance liquid chromatography (HPLC) with a fluorescence detector were identical with those of authentic PAHs. Gas chromatography-mass spectrometry of some HPLC fractions demonstrated that anthraquinone, azulene derivative, quinoline derivative, chrysene and benzo[b]fluoranthene are probably contained in these fractions.

  9. Comparison between carcinogenicity and mutagenicity based on chemicals evaluated in the IARC monographs.

    PubMed Central

    Bartsch, H; Tomatis, L

    1983-01-01

    The qualitative relationship between carcinogenicity and mutagenicity (DNA-damaging activity), based on chemicals which are known to be or suspected of being carcinogenic to man and/or to experimental animals, is analyzed using 532 chemicals evaluated in Volumes 1-25 of the IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. About 40 compounds (industrial processes) were found to be either definitely or probably carcinogenic to man, and 130 chemicals have been adequately tested in rodents and most of them also in various short-term assays. For a comparison between the carcinogenicity of a chemical and its behavior in short-term tests, systems were selected that have a value for predicting carcinogenicity. These were divided into mutagenicity in (A) the S. typhimurium/microsome assay, (B) other submammalian systems and (C) cultured mammalian cells; (D) chromosomal abnormalities in mammalian cells; (E) DNA damage and repair; (F) cell transformation (or altered growth properties) in vitro. The following conclusions can be drawn. In the absence of studies in man, long-term animal tests are still today the only ones capable of providing evidence of the carcinogenic effect of a chemical. The development and application of an appropriate combination of short-term tests (despite current limitations) can significantly contribute to the prediction/confirmation of the carcinogenic effects of chemicals in animals/man. Confidence in positive tests results is increased when they are confirmed in multiple short-term tests using nonrepetitive end points and different activation systems. Assays to detect carcinogens which do not act via electrophiles (promoters) need to be developed. The results of a given short-term test should be interpreted in the context of other toxicological data. Increasing demand for quantitative carcinogenicity data requires further examination of whether or not there is a quantitative relationship between the potency of a

  10. Mutagenicity and clastogenicity of extracts of Helicobacter pylori detected by the Ames test and in the micronucleus test using human lymphoblastoid cells.

    PubMed

    Arimoto-Kobayashi, Sakae; Ohta, Kaori; Yuhara, Yuta; Ayabe, Yuka; Negishi, Tomoe; Okamoto, Keinosuke; Nakajima, Yoshihiro; Ishikawa, Takeshi; Oguma, Keiji; Otsuka, Takanao

    2015-07-01

    Epidemiological studies have demonstrated a close association between infection with Helicobacter pylori (H.pylori) and the development of gastric carcinoma. Chronic H.pylori infection increases the frequency of mutation in gastric epithelial cells. However, the mechanism by which infection of H.pylori leads to mutation in gastric epithelial cells is unclear. We suspected that components in H.pylori may be related to the mutagenic response associated with DNA alkylation, and could be detected with the Ames test using a more sensitive strain for alkylating agents. Our investigation revealed that an extract of H.pylori was mutagenic in the Ames test with Salmonella typhimurium YG7108, which is deficient in the DNA repair of O(6)-methylguanine. The extract of H.pylori may contain methylating or alkylating agents, which might induce O (6)-alkylguanine in DNA. Mutagenicity of the alkylating agents N-methyl-N-nitrosourea (MNU) and N-methyl-N'-nitro-N-nitrosoguanidine in the Ames test with S.typhimurium TA1535 was enhanced significantly in the presence of the extract of H.pylori. The tested extracts of H.pylori resulted in a significant induction of micronuclei in human-derived lymphoblastoid cells. Heat instability and dialysis resistance of the extracts of H.pylori suggest that the mutagenic component in the extracts of H.pylori is a heat-unstable large molecule or a heat-labile small molecule strongly attached or adsorbed to a large molecule. Proteins in the extracts of H.pylori were subsequently fractionated using ammonium sulphate precipitation. However, all fractions expressed enhancing effects toward MNU mutagenicity. These results suggest the mutagenic component is a small molecule that is absorbed into proteins in the extract of H.pylori, which resist dialysis. Continuous and chronic exposure of gastric epithelial cells to the alkylative mutagenic component from H.pylori chronically infected in the stomach might be a causal factor in the gastric carcinogenesis

  11. Discerning the Chemical Composition and Mutagenic Effects of Soy Biodiesel PM

    EPA Science Inventory

    Discerning the Chemical Composition and Mutagenic Effects of Soy Biodiesel PM David G. Nashab, Esra Mutluc, William T. Prestond, Michael D. Haysb, Sarah H. Warrenc, Charly Kingc, William P. Linakb, M. lan Gilmourc, and David M. DeMarinic aOak Ridge Institute for Science and Ed...

  12. Mutagenicity of ω-3 fatty acid peroxidation products in the Ames test.

    PubMed

    Grúz, Petr; Shimizu, Masatomi; Sugiyama, Kei-Ichi; Honma, Masamitsu

    2017-07-01

    Polyunsaturated fatty acids (PUFA) represent one of the main building blocks of cellular membranes and their varying composition impacts lifespan as well as susceptibility to cancer and other degenerative diseases. Increased intake of ω-3 PUFA is taught to compensate for the abundance of ω-6 PUFA in modern human diet and prevent cardiocirculatory diseases. However, highly unsaturated PUFA of marine and seed origin easily oxidize to aldehydic products which form DNA adducts. With increased PUFA consumption it is prudent to re-evaluate ω-3 PUFA safety and the genotoxic hazards of their metabolites. We have used the standard Ames test to examine the mutagenicity of 2 hexenals derived from lipid peroxidation of the common ω-3 PUFA in human diet and tissues. Both 4-hydroxyhexenal and 2-hexenal derived from the ω-3 docosahexaenoic and α-linolenic acid, respectively, induced base substitutions in the TA104 and TA100 Ames strains in a dose dependent manner. Their mutagenicity was dependent on the Y-family DNA polymerase RI and they did not induce other types of mutations such as the -2 and -1 frameshifts in the TA98 and TA97 strains. Our results expand previous findings about the mutagenicity of related ω-3 peroxidation product 4-oxohexenal and raise alert that overuse of ω-3 rich oils may have adverse effect on genome stability. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Ames and random amplified polymorphic DNA tests for the validation of the mutagenic and/or genotoxic potential of the drinking water disinfection by-products chloroform and bromoform.

    PubMed

    Khallef, Messaouda; Cenkci, Süleyman; Akyil, Dilek; Özkara, Arzu; Konuk, Muhsin; Benouareth, Djamel Eddine

    2018-01-28

    Chloroform and Bromoform are two abundant trihalomethanes found in Algerian drinking water. The investigation of the mutagenic hazard of these disinfection by-products was studied by Ames test as prokaryotic bioassay to show their mutagenic effects. For this, Salmonella typhimurium TA98 and TA100 strains were employed. Both chloroform and bromoform showed a direct mutagenic effect since the number of revertant colonies gradually increase in dose-dependent manner with all concentrations tested with the two bacterial strains and these were both in the absence and presence of S9 metabolic activation. The genotoxic hazard was also studied by random amplified polymorphic DNA test on the root cells of Allium cepa as eukaryotic bioassay. DNA extracted from the roots of the onion were incubated at different concentrations of chloroform and bromoform and then amplified by polymerase chain reaction. This was based on demonstrating a major effect of disappearance of bands compared to roots incubated in the negative control (distilled water). The results showed that these two compounds affected genomic DNA by breaks although by mutations.

  14. Water mutagenic potential assessment on a semiarid aquatic ecosystem under influence of heavy metals and natural radioactivity using micronuclei test.

    PubMed

    Chaves, Luiz Cláudio Cardozo; Navoni, Julio Alejandro; de Morais Ferreira, Douglisnilson; Batistuzzo de Medeiros, Silvia; Ferreira da Costa, Thomas; Petta, Reinaldo Antônio; Souza do Amaral, Viviane

    2016-04-01

    The contamination of water bodies by heavy metals and ionizing radiation is a critical environmental issue, which can affect water quality and, thus, human health. This study aimed to evaluate the water quality of the Boqueirão de Parelhas Dam in the Brazilian semiarid region. A 1-year study (2013-2014) was performed through the assessment of physicochemical parameters, heavy metal content, and radioactivity along with the mutagenicity potential of water using micronuclei test in Orechromis niloticus (in vivo) and the cytokinesis-block micronucleus (CBMN) assay in human lymphocytes (in vitro). A deterioration of water organoleptics characteristics by the presence of high levels of sulfate and total solids was observed. High concentrations of aluminum, nickel, silver, and lead along with the alpha particle content were higher than the limits suggested by the World Health Organization and Brazilian legislation for drinking water. An increase in the frequency of micronuclei and nuclear abnormalities was observed in both experimental models. The results obtained confirmed the mutagenic potential present in water samples. This study highlights that geogenic agents affect water quality becoming a human health concern to be taken into account due to the relevance that this water reservoir has in the region.

  15. Quantitative changes in endogenous DNA damage correlate with conazole mutagenicity and tumorigenicity.

    EPA Science Inventory

    The mouse liver tumorigenic conazolefungicides triadimefon and propiconazole have previously been shown to be in vivo mouse liver mutagens in the Big Blue" transgenic mutation assay when administered in feed at tumorigenic doses, whereas the nontumorigenic conazole myclobutanil w...

  16. Comparative studies on the lethal, mutagenic, and recombinogenic effects of ultraviolet -A, -B, -C, and visible light with and without 8-methoxypsoralen in Saccharomyces cerevisiae.

    PubMed

    Mondon, P; Shahin, M M

    1992-05-01

    Genetic effects of UV-A, UV-B, UV-C, and the combination of 8-methoxypsoralen (8-MOP) with UV-A or visible light were studied in the haploid strain XV185-14C and diploid strain D5 of Saccharomyces cerevisiae. The induction of his+, lys+, and hom+ reverse mutations was measured in strain XV185-14C. In strain D5 we measured the induction of genetically altered colonies, particularly twin spot colonies arising from a mitotic crossing-over. UV-C and UV-B induced point mutations at the three loci in the haploid strain and mitotic crossing-over and other genetic alterations in the diploid strain. UV-C was more mutagenic and recombinogenic than UV-B. UV-A or visible light alone did not induce genotoxic effects at the doses tested. However, UV-A plus 8-MOP produced lethal and mutagenic effects in the haploid strain XV185-14C, although mutagenic activity was less than that of UV-B. Visible light plus 8-MOP also induced genotoxic effects in strain XV185-14C. In the diploid strain D5, UV-A plus 8-MOP induced a higher frequency of genetic alterations than UV-B at comparative doses. Visible light plus 8-MOP was also genetically active in strain D5. The haploid strain was more sensitive to the lethal effects of UV-C, UV-B, UV-A, and impure visible light plus 8-MOP than the diploid strain.

  17. Chemical analysis and toxicity of seaweed extracts with inhibitory activity against tropical fruit anthracnose fungi.

    PubMed

    Machado, Levi Pompermayer; Matsumoto, Silvia Tamie; Jamal, Claudia Masrouah; da Silva, Marcelo Barreto; Centeno, Danilo da Cruz; Colepicolo Neto, Pio; de Carvalho, Luciana Retz; Yokoya, Nair S

    2014-07-01

    Banana and papaya are among the most important crops in the tropics, with a value amounting to millions of dollars per year. However, these fruits suffer significant losses due to anthracnose, a fungal disease. It is well known that certain seaweed extracts possess antifungal activity, but no published data appear to exist on the practical application of this property. In the present study, five organic Brazilian seaweed extracts were screened for their activity against banana and papaya anthracnose fungi. Furthermore, cytotoxic and mutagenic effects of the extracts were evaluated by the brine shrimp lethality assay and the Allium cepa root-tip mutagenicity test respectively, while their major components were identified by gas chromatography/mass spectrometry. Strong fungus-inhibitory effects of Ochtodes secundiramea and Laurencia dendroidea extracts were observed on both papaya (100 and 98% respectively) and banana (89 and 78% respectively). This impressive activity could be associated with halogenated terpenes, the major components of both extracts. Only Hypnea musciformis extract showed cytotoxic and mutagenic effects. The results of this study suggest the potential use of seaweed extracts as a source of antifungal agents with low toxicity to control anthracnose in papaya and banana during storage. © 2013 Society of Chemical Industry.

  18. Mutagenic atmospheres resulting from the photooxidation of aromatic hydrocarbon and NOx mixtures

    EPA Science Inventory

    Although many volatile organic compounds (VOCs) are regulated to limit air pollution and the consequent health effects, the photooxidation products generally are not. Thus, we examined the mutagenicity in Salmonella TA100 of photochemical atmospheres generated in a steady-state a...

  19. Modulatory effects of metformin on mutagenicity and epithelial tumor incidence in doxorubicin-treated Drosophila melanogaster.

    PubMed

    Oliveira, Victor Constante; Constante, Sarah Alves Rodrigues; Orsolin, Priscila Capelari; Nepomuceno, Júlio César; de Rezende, Alexandre Azenha Alves; Spanó, Mário Antônio

    2017-08-01

    Metformin (MET) is an anti-diabetic drug used to prevent hepatic glucose release and increase tissue insulin sensitivity. Diabetic cancer patients are on additional therapy with anticancer drugs. Doxorubicin (DXR) is a cancer chemotherapeutic agent that interferes with the topoisomerase II enzyme and generates free radicals. MET (2.5, 5, 10, 25 or 50 mM) alone was examined for mutagenicity, recombinogenicity and carcinogenicity, and combined with DXR (0.4 mM) for antimutagenicity, antirecombinogenicity and anticarcinogenicity, using the Somatic Mutation and Recombination Test and the Test for Detecting Epithelial Tumor Clones in Drosophila melanogaster. MET alone did not induce mutation or recombination. Modulating effects of MET on DXR-induced DNA damage were observed at the highest concentrations. In the evaluation of carcinogenesis, MET alone did not induce tumors. When combined with DXR, MET also reduced the DXR-induced tumors at the highest concentrations. Therefore, in the present experimental conditions, MET alone did not present mutagenic/recombinogenic/carcinogenic effects, but it was able to modulate the effect of DXR in the induction of DNA damage and of tumors in D. melanogaster. It is believed that this modulating effect is mainly related to the antioxidant, anti-inflammatory and apoptotic effects of this drug, although such effects have not been directly evaluated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Quantitative changes in endogenous DNA adducts correlate with conazole in vivo mutagenicity and tumorigenicity.

    PubMed

    Ross, Jeffrey A; Leavitt, Sharon A; Schmid, Judith E; Nelson, Garret B

    2012-09-01

    The mouse liver tumorigenic conazole fungicides triadimefon and propiconazole have previously been shown to be in vivo mouse liver mutagens in the Big Blue™ transgenic mutation assay when administered in feed at tumorigenic doses, whereas the nontumorigenic conazole myclobutanil was not mutagenic. DNA sequencing of the mutants recovered from each treatment group as well as from animals receiving control diet revealed that propiconazole- and triadimefon-induced mutations do not represent general clonal expansion of background mutations, and support the hypothesis that they arise from the accumulation of endogenous reactive metabolic intermediates within the liver in vivo. We therefore measured the spectra of endogenous DNA adducts in the livers of mice from these studies to determine if there were quantitative or qualitative differences between mice receiving tumorigenic or nontumorigenic conazoles compared to concurrent control animals. We resolved and quantitated 16 individual adduct spots by (32)P postlabelling and thin layer chromatography using three solvent systems. Qualitatively, we observed the same DNA adducts in control mice as in mice receiving conazoles. However, the 13 adducts with the highest chromatographic mobility were, as a group, present at significantly higher amounts in the livers of mice treated with propiconazole and triadimefon than in their concurrent controls, whereas this same group of DNA adducts in the myclobutanil-treated mice was not different from controls. This same group of endogenous adducts were significantly correlated with mutant frequency across all treatment groups (P = 0.002), as were total endogenous DNA adduct levels (P = 0.005). We hypothesise that this treatment-related increase in endogenous DNA adducts, together with concomitant increases in cell proliferation previously reported to be induced by conazoles, explain the observed increased in vivo mutation frequencies previously reported to be induced by treatment with

  1. 1H NMR study of the hetero-association of flavin-mononucleotide with mutagenic dyes: ethidium bromide and proflavine

    NASA Astrophysics Data System (ADS)

    Evstigneev, M. P.; Mukhina, Yu. V.; Davies, D. B.

    The hetero-association of the vitamin B2 derivative, flavin-mononucleotide (FMN), with a mutagenic dye, ethidium bromide (EB) or proflavine (PF), has been studied by 1D and 2D 500 MHz 1H NMR spectroscopy. The variations of proton chemical shifts of both the vitamin and dye as a function of concentration and temperature were analysed in terms of the structural and thermodynamical properties of the FMN-EB and FMN-PF complexes in solution. The structures of the complexes were also investigated by observed intermolecular ROE contacts and molecular mechanics calculations. The results show that the 1 : 1 hetero-association complexes in solution are more stable than the self-association complexes, which is consistent with formation of an intermolecular hydrogen-bond in the hetero-complexes of FMN-EB and FMN-PF. Hence it is possible that the toxicity of aromatic molecules such as EB and PF may be reduced in vitro by the presence of FMN, partly because of the known antimutagenic action of FMN and partly because it has been shown in this work that there is an effective intermolecular association between the mutagens and the vitamin.

  2. Mutagenicity study of weeds and common plants used in traditional medicine and for animal feed.

    PubMed

    Thepouyporn, Apanchanid; Kwanbunjan, Karunee; Pooudong, Somchai; Changbumrung, Supranee

    2006-01-01

    Mutagenicity and antimutagenicity potentials were tested using Ames' test in crude distilled water and absolute ethanol extracts from the stems and leaves of Peperomia pellucida (Linn.) Kunth, Eichhornia crassipes Solms, Colocasia esculenta Schott and Brachiaria mutica (Forssk.) Stapf, and the stems of Musa sapientum Linn. No mutagenic effect was found in any of the 10 mg/plate crude extracts of these plants for either TA98 or TA100 of Salmonella typhimurium, in a direct test and a mutagenic induced test by S-9 mix. Both distilled water and absolute ethanol extract of 0.5-10 mg/plate B. mutica showed strong antimutagenicity to AFB1, B(a)P and 4NQO in two tester strains. Ethanol extract of 0.1-0.5 mg/plate C. esculenta also showed antimutagenicity to AFB1, B(a)P and 4NQO in two tester strains, but the 0.5-10 mg/plate water extract had an antimutagenic effect only for B(a)P in TA98. The ethanol extracts of 5 mg/plate B. mutica and 0.5 mg/plate C. esculenta are cytotoxic, as indicated by their partial killing effect.

  3. Mutagenic potential of Cordia ecalyculata alone and in association with Spirulina maxima for their evaluation as candidate anti-obesity drugs.

    PubMed

    Araldi, R P; Rechiutti, B M; Mendes, T B; Ito, E T; Souza, E B

    2014-07-07

    Obesity is one of the most important nutritional disorders, and can be currently considered as an epidemic. Although there are few weight reduction drugs available on the market, some new drug candidates have been proposed, including Cordia ecalyculata, a Brazilian plant with anorectic properties, and Spirulina maxima, a cyanobacterium with antioxidant and anti-genotoxic activity. In this study, we evaluated the mutagenic potential of C. ecalyculata at doses of 150, 300, and 500 mg/kg alone and in association with S. maxima at doses of 75, 150, and 250 mg/kg, respectively, through an in vivo micronucleus test, using mice of both sexes, and an in vitro micronucleus test and comet assay, using human peripheral blood. For all tests, cyclophosphamide was used as a positive control. The results showed that treatment of 300 mg/kg C. ecalyculata and the combination treatment of 500 mg/kg C. ecalyculata with 250 mg/kg S. maxima resulted in anorectic effects. The mutagenic tests did not reveal any clastogenic or genotoxic activity for any treatment, indicating that these candidates could be marketed as weight-reduction drugs. Moreover, the drugs contain chemo-preventive substances that can protect against tumorigenesis, which has been associated with obesity.

  4. Reevaluation of the effect of ellagic acid on N-methyl-N-nitrosourea DNA alkylation and mutagenicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lord, H.L.; Josephy, P.D.; Snieckus, V.A.

    N-Methyl-N-nitrosourea (MNU) is a reactive, mutagenic methylating agent. MNU methylates DNA at various sites, including guanine N{sup 7}, guanine O{sup 6}, and adenine N{sup 3}. Dixit and Gold ((1986) Proc. Natl, Acad. Sci. U.S.A. 83, 8039-8043) reported that ellagic acid, a phenolic natural product, inhibited the mutagenicity of MNU in Salmonella typhimurium strain TA 100, inhibited salmon sperm DNA alkylation by ({sup 3}H)MNU, and also greatly reduced the ratio of guanine O{sup 6} to guanine N{sup 7} alkylation. We have examined the MNU-induced alkylation of calf thymus DNA and evaluated the effect of ellagic acid on this binding. Ellagic acidmore » had only a slight effect on total alkylation and did not alter the ratio of methylation at guanine-O{sup 6} and -N{sup 7} positions. In further experiments, ellagic acid did not significantly inhibit MNU mutagenicity. These findings do not support the potential use of ellagic acid as an inhibitor of biological damage induced by nitrosoureas.« less

  5. Induction of a bystander mutagenic effect of alpha particles in mammalian cells

    NASA Technical Reports Server (NTRS)

    Zhou, H.; Randers-Pehrson, G.; Waldren, C. A.; Vannais, D.; Hall, E. J.; Hei, T. K.; Chatterjee, A. (Principal Investigator)

    2000-01-01

    Ever since the discovery of X-rays was made by Rontgen more than a hundred years ago, it has always been accepted that the deleterious effects of ionizing radiation such as mutation and carcinogenesis are attributable mainly to direct damage to DNA. Although evidence based on microdosimetric estimation in support of a bystander effect appears to be consistent, direct proof of such extranuclear/extracellular effects are limited. Using a precision charged particle microbeam, we show here that irradiation of 20% of randomly selected A(L) cells with 20 alpha particles each results in a mutant fraction that is 3-fold higher than expected, assuming no bystander modulation effect. Furthermore, analysis by multiplex PCR shows that the types of mutants induced are significantly different from those of spontaneous origin. Pretreatment of cells with the radical scavenger DMSO had no effect on the mutagenic incidence. In contrast, cells pretreated with a 40 microM dose of lindane, which inhibits cell-cell communication, significantly decreased the mutant yield. The doses of DMSO and lindane used in these experiments are nontoxic and nonmutagenic. We further examined the mutagenic yield when 5-10% of randomly selected cells were irradiated with 20 alpha particles each. Results showed, likewise, a higher mutant yield than expected assuming no bystander effects. Our studies provide clear evidence that irradiated cells can induce a bystander mutagenic response in neighboring cells not directly traversed by alpha particles and that cell-cell communication process play a critical role in mediating the bystander phenomenon.

  6. Method for identifying mutagenic agents which induce large, multilocus deletions in DNA

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bradley, W.E.C.; Belouchi, A.; Dewyse, P.

    1993-07-13

    A method of identifying a mutagenic agent is described which includes a large, multilocus deletions in DNA in mammalian cells comprising: (i) exposing a class III heterozygous CHO cell line to a potential mutagenic agent under investigation, and allowing any mutation of the cell line to proceed, said cell line being characterized in that a restriction fragment length variation exists in on mutation it becomes resistant to 2,6-diaminopurine and in that the DNA sequence adjacent to the two alleles of the APRT gene such that the DNA sequence adjacent to one of the two alleles can be digested with themore » enzyme BclI but the DNA sequence variation adjacent to the other of the two alleles cannot be digested with BclI, (ii) isolating induced mutations of the cell line deficient in APRT function, (iii) isolating DNA from the induced mutants, (iv) digesting the isolated DNA with BclI enzyme to produce digested fragments including a 19 kb fragment and any 2 kb fragment, which fragments hybridize with the labeled probe derived from DNA fragment PDI, (v) separating any digested fragments, (vi) transferring the separated fragments of (v) to a solid support, (vii) hybridizing the supported separated fragments with a labeled probe derived from the clone DNA fragment PD 1, (viii) determining fragments having undergone loss of the 2 kb band identified by the probe, as an identification of parent mutants in which the loss occurred, and (ix) evaluating the mutating ability of the potential mutagenic agent.« less

  7. DNA adducts of ethylene dibromide: Aspects of formation and mutagenicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cmarik, J.L.

    1,2-Dibromoethane (ethylene dibromide, EDB), a potential human carcinogen, undergoes bioactivation by the pathway of glutathione (GSH) conjugation, which generates a reactive intermediate capable of alkylating DNA. The major DNA adduct formed is S-[2-(N[sup 7]-guanyl)ethyl]GSH. This dissertation examined the bioactivation of EDB and the formation of DNA adducts. The selectivity of purified rat and human GSH S-transferases for EDB was examined in vitro. An assay was developed to measure the formation of S,S[prime]-ethylene-bis(GSH). The [alpha] class of the GSH S-transferases was responsible for the majority of EDB-GSH conjugation with both the rat and human enzymes. Human tissue samples for a victimmore » of EDB poisoning were analyzed for S-[2-(N[sup 7]-guanyl)ethyl]GSH utilizing electrochemical detection. No adducts were detected in samples of brain, heart, or kidney. The pattern of alkylation of guanines in fragments of plasmid pBR322 DNA by S-(2-chloroethyl)GSH and related compounds was determined. Alkylation varied approximately ten-fold in intensity and was strongest in runs of guanines. Few differences were observed in the alkylation patterns generated by the different compounds tested. The spectrum of mutations caused by S-(2-chloroethyl)GSH was determined using an M13 bacteriophage forward mutation assay. The majority of mutations (70%) were G:C to A:T transitions. Participation of the N[sup 7]-guanyl adduct in the mutagenic process is strongly implicated. The sequence selectivity of alkylation in the region of M13 sequenced in the mutation assay was determined. Comparison of the sequence selectivity with the mutation spectrum revealed no obligate relationship between the extent of adduct formation and the number of mutations which resulted at different sites. Sequence context appears to exert a strong influence on the processing of lesions. These studies strongly implicate S-[2-(N[sup 7]-guanyl)-ethyl]GSH as a mutagenic lesion formed by EDB.« less

  8. MUTAGENICITY IN SALMONELLA OF SULFUR-CONTAINING POLYCYCLIC AROMATIC HETEROCYCLES AND THEIR DIHYDRODIOL DERIVATIVES

    EPA Science Inventory

    Polycyclic aromatic sulfur heterocycles (PASH) are common constituents of cigarette smoke, fossil fuel-derived materials, and their combustion byproducts. Many PASH are known mutagens and carcinogens. However, unlike their nonsulfur-containing counterparts, relatively little is k...

  9. Evolutionary Ensemble for In Silico Prediction of Ames Test Mutagenicity

    NASA Astrophysics Data System (ADS)

    Chen, Huanhuan; Yao, Xin

    Driven by new regulations and animal welfare, the need to develop in silico models has increased recently as alternative approaches to safety assessment of chemicals without animal testing. This paper describes a novel machine learning ensemble approach to building an in silico model for the prediction of the Ames test mutagenicity, one of a battery of the most commonly used experimental in vitro and in vivo genotoxicity tests for safety evaluation of chemicals. Evolutionary random neural ensemble with negative correlation learning (ERNE) [1] was developed based on neural networks and evolutionary algorithms. ERNE combines the method of bootstrap sampling on training data with the method of random subspace feature selection to ensure diversity in creating individuals within an initial ensemble. Furthermore, while evolving individuals within the ensemble, it makes use of the negative correlation learning, enabling individual NNs to be trained as accurate as possible while still manage to maintain them as diverse as possible. Therefore, the resulting individuals in the final ensemble are capable of cooperating collectively to achieve better generalization of prediction. The empirical experiment suggest that ERNE is an effective ensemble approach for predicting the Ames test mutagenicity of chemicals.

  10. URINARY MUTAGENICITY IN CHARCOAL WORKERS: A CROSS-SECTIONAL STUDY IN NORTHEASTERN BRAZIL

    EPA Science Inventory

    Urinary Mutagenicity in charcoal workers: a cross-sectional study in northeastern Brazil

    Charcoal production by wood carbonization is an ancient process that has changed little since the Bronze Age. Its production in large scale is necessary to sustain some steel and pig...

  11. Dose and temporal evaluation of ethylene oxide-induced mutagenicity in the lungs of male big blue mice following inhalation exposure to carcinogenic concentrations.

    PubMed

    Manjanatha, Mugimane G; Shelton, Sharon D; Chen, Ying; Parsons, Barbara L; Myers, Meagan B; McKim, Karen L; Gollapudi, B Bhaskar; Moore, Nigel P; Haber, Lynne T; Allen, Bruce; Moore, Martha M

    2017-04-01

    Ethylene oxide (EO) is a direct acting alkylating agent; in vitro and in vivo studies indicate that it is both a mutagen and a carcinogen. However, it remains unclear whether the mode of action (MOA) for cancer for EO is a mutagenic MOA, specifically via point mutation. To investigate the MOA for EO-induced mouse lung tumors, male Big Blue (BB) B6C3F1 mice (10/group) were exposed to EO by inhalation, 6 hr/day, 5 days/week for 4 (0, 10, 50, 100, or 200 ppm EO), 8, or 12 weeks (0, 100, or 200 ppm EO). Lung DNA samples were analyzed for cII mutant frequency (MF) at 4, 8 and 12 weeks of exposure; the mutation spectrum was analyzed for mutants from control and 200 ppm EO treatments. Although EO-induced cII MFs were 1.5- to 2.7-fold higher than the concurrent controls at 4 weeks, statistically significant increases in the cII MF were found only after 8 and 12 weeks of exposure and only at 200 ppm EO (P ≤ 0.05), which is twice the highest concentration used in the cancer bioassay. Consistent with the positive response, DNA sequencing of cII mutants showed a significant shift in the mutational spectra between control and 200 ppm EO following 8 and 12 week exposures (P ≤ 0.035), but not at 4 weeks. Thus, EO mutagenic activity in vivo was relatively weak and required higher than tumorigenic concentrations and longer than 4 weeks exposure durations. These data do not follow the classical patterns for a MOA mediated by point mutations. Environ. Mol. Mutagen. 58:122-134, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. Predictive Models for Carcinogenicity and Mutagenicity: Frameworks, State-of-the-Art, and Perspectives

    EPA Science Inventory

    Mutagenicity and carcinogenicity are endpoints of major environmental and regulatory concern. These endpoints are also important targets for development of alternative methods for screening and prediction due to the large number of chemicals of potential concern and the tremendou...

  13. Predictive Models for Carcinogenicity and Mutagenicity: Frameworks,State-of-the-Art, and Perspectives

    EPA Science Inventory

    Mutagenicity and carcinogenicity are endpoints of major environmental and regulatory concern. These endpoints are also important targets for development of alternative methods for screening and prediction due to the large number of chemicals of potential concern and the tremendou...

  14. Carcinogenicity and Mutagenicity Data: New Initiatives to Improve Access and Utility for Modeling

    EPA Science Inventory

    Currents models for prediction of chemical carcinogenicity and mutagenicity rely upon a relatively small number of publicly available data resources, where the data being modeled are highly summarized and aggregated representations of the actual experimental results. A number of...

  15. Formation and fate of gaseous and particulate mutagens and carcinogens in real and simulated atmospheres.

    PubMed Central

    Pitts, J N

    1983-01-01

    The growing use of coal for heating and electric power generation and diesel engines in light duty motor vehicles will increase not only the existing atmospheric concentrations of criteria pollutants such as NO2, SO2, O3 and fine particulates, but also the concentrations of a number of highly reactive gaseous copollutants such as HONO, HONO2, PAN and the nitrate radical, NO3. These gaseous noncriteria pollutants are of interest not only because of their roles in the chemistry of the "clean" and polluted troposphere, including "acid rain," but also because they may pose health risks disproportionate to their relatively low ambient concentrations, and through complex heterogeneous reactions, they may serve as precursors or catalysts in the formation of "nonclassical" particulate mutagens and carcinogens such as certain nitroarenes associated with combustion generated particulate polycyclic organic matter (POM). Results of research efforts to establish current ambient levels of these noncriteria pollutants and to develop an understanding of their sources, formation and sinks are reported here. First, long pathlength (greater than or equal to 1 km) infrared and UV-visible spectroscopic studies of ambient levels of gaseous HONO, NO3, HONO2, PAN, HCHO and HCOOH in southern California atmospheres are described, and data given on their ambient concentrations. Second, an integrated chemical/microbiological investigation is described. It is directed toward identifying the nature of direct-acting mutagens found in extracts of diesel and ambient POM, as well as those formed upon exposure of environmentally relevant PAH to simulated natural and polluted atmospheres. The identification of certain of these mutagens, including a newly identified class of mutagenic PAH-lactones is discussed, along with the mechanisms of their formation and fate in the natural and polluted troposphere. PMID:6337822

  16. Meat-cooking mutagens and risk of renal cell carcinoma

    PubMed Central

    Daniel, C R; Schwartz, K L; Colt, J S; Dong, L M; Ruterbusch, J J; Purdue, M P; Cross, A J; Rothman, N; Davis, F G; Wacholder, S; Graubard, B I; Chow, W H; Sinha, R

    2011-01-01

    Background: High-temperature cooked meat contains two families of carcinogens, heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Given the kidneys' role in metabolism and urinary excretion of these compounds, we investigated meat-derived mutagens, as well as meat intake and cooking methods, in a population-based case–control study conducted in metropolitan Detroit and Chicago. Methods: Newly diagnosed, histologically confirmed adenocarcinoma of the renal parenchyma (renal cell carcinoma (RCC)) cases (n=1192) were frequency matched on age, sex, and race to controls (n=1175). The interviewer-administered Diet History Questionnaire (DHQ) included queries for meat-cooking methods and doneness with photographic aids. Levels of meat mutagens were estimated using the DHQ in conjunction with the CHARRED database. Results: The risk of RCC increased with intake of barbecued meat (Ptrend=0.04) and the PAH, benzo(a)pyrene (BaP) (multivariable-adjusted odds ratio and 95% confidence interval, highest vs lowest quartile: 1.50 (1.14, 1.95), Ptrend=0.001). With increasing BaP intake, the risk of RCC was more than twofold in African Americans and current smokers (Pinteraction<0.05). We found no association for HCAs or overall meat intake. Conclusion: BaP intake, a PAH in barbecued meat, was positively associated with RCC. These biologically plausible findings advocate further epidemiological investigation into dietary intake of BaP and risk of RCC. PMID:21897389

  17. Can Spirulina maxima reduce the mutagenic potential of sibutramine?

    PubMed

    Araldi, R P; Santos, N P; Mendes, T B; Carvalho, L B; Ito, E T; de-Sá-Júnior, P L; Souza, E B

    2015-12-28

    The worldwide obesity pandemic requires the use of anti-obesity drugs. Sibutramine is an anti-obesity drug that has been used worldwide but is indiscriminately consumed in Brazil. Several studies have demonstrated that sibutramine promotes weight loss and weight maintenance, but several side effects have been associated with its systematic consumption. For this reason, sibutramine was withdrawn from the European and American markets, but still remains legal for use in Brazil. Studies have shown that a 5-10% reduction in body weight results in outstanding health benefits for obese patients. However, in order to promote significant weight loss, it is necessary to use sibutramine for at least 2 years. This long-term exposure has carcinogenic potential, as sibutramine causes DNA damage. Thus, this study evaluated the in vivo mutagenic potential of sibutramine alone (5, 7, 10, 15, and 20 mg/kg) and in association with Spirulina maxima (150 and 300 mg/kg), a cyanobacterium with antioxidant potential, using the polychromatic erythrocyte micronucleus test. Our results reinforced the mutagenic potential of sibutramine alone, which showed a time-dependent action. Combinatory treatments with S. maxima were not able to reduce the genotoxicity of sibutramine. These results were confirmed in vitro with the cytokinesis-blocked micronucleus test. In conclusion, our data showed that new alternative anti-obesity treatments are needed since the consumption of sibutramine can increase the risk of cancer in overweight patients.

  18. In vivo mutagenicity of conazole fungicides correlates with tumorigenicity.

    PubMed

    Ross, Jeffrey A; Moore, Tanya; Leavitt, Sharon A

    2009-03-01

    Triadimefon, propiconazole and myclobutanil are conazoles, an important class of agricultural and therapeutic fungicides. Triadimefon and propiconazole are mouse liver tumorigens, while myclobutanil is not. All three conazoles are generally inactive in short-term genotoxicity tests. We studied the in vivo mutagenicity of these three conazoles using the Big Blue mouse assay system. Groups of mice were fed either control diet or diet containing 1800 p.p.m. triadimefon, 2500 p.p.m. propiconazole or 2000 p.p.m. myclobutanil. After 4 days of feeding, mice were immediately euthanized, livers were removed, DNA isolated and lacI genes recovered into infectious bacteriophage lambda particles by in vitro packaging. Bacteriophage with mutations in the lacI gene was detected by infecting into Escherichia coli, and mutant frequencies were determined using a colorimetric plaque assay. Propiconazole induced a 1.97-fold increase in mutant frequency compared to concurrent controls (P = 0.018) and triadimefon induced a 1.94-fold increase compared to concurrent controls (P = 0.009). Myclobutanil did not induce any change in mutant frequency (P = 0.548). These results provide the first evidence that the hepatotumorigenic conazoles are capable of inducing mutations in liver in vivo while the non-tumorigen myclobutanil is not, suggesting that mutagenicity may represent a key event in conazoles tumorigenic mode of action.

  19. MUTAGENIC PROPERTIES OF RIVER WATERS FLOWING THROUGH BIG CITY AREAS IN NORTH AMERICA

    EPA Science Inventory

    The hanging technique using Blue rayon, which specifically adsorbs mutagens with multicyclic planer structures, has advantages over the conventional method of bringing-large volumes of water back to the laboratory for extraction. Therefore, the analysis of many samples from remot...

  20. Microsomal P-450 induction by some secondary products from thermal oxidation of dietary lipids: epidermal hyperplasia, mutagenicity and cytochrome P-450 activities.

    PubMed

    Crawford, L; Wheeler, E L

    1983-12-01

    Distillable secondary products from roasted fowl were found to be cytotoxic but not mutagenic when assayed with Salmonella typhimurium strains TA98, TA100 and TA1537. A crudely separated fraction of the volatiles produced focal hyperplasia and damage to the epidermis of the backs of mice. The volatiles also caused an apparent synthesis of non-constitutive forms of rat hepatic cytochromes P-450 which metabolize benzo[a]pyrene B [a]P differently from the constitutive P-450.

  1. Trichloroethylene Biotransformation and its Role in Mutagenicity, Carcinogenicity and Target Organ Toxicity

    PubMed Central

    Lash, Lawrence H.; Chiu, Weihsueh A.; Guyton, Kathryn Z.; Rusyn, Ivan

    2014-01-01

    Metabolism is critical for the mutagenicity, carcinogenicity, and other adverse health effects of trichloroethylene (TCE). Despite the relatively small size and simple chemical structure of TCE, its metabolism is quite complex, yielding multiple intermediates and end-products. Experimental animal and human data indicate that TCE metabolism occurs through two major pathways: cytochrome P450 (CYP)-dependent oxidation and glutathione (GSH) conjugation catalyzed by GSH S-transferases (GSTs). Herein we review recent data characterizing TCE processing and flux through these pathways. We describe the catalytic enzymes, their regulation and tissue localization, as well as the evidence for transport and inter-organ processing of metabolites. We address the chemical reactivity of TCE metabolites, highlighting data on mutagenicity of these end-products. Identification in urine of key metabolites, particularly trichloroacetate (TCA), dichloroacetate (DCA), trichloroethanol and its glucuronide (TCOH and TCOG), and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NAcDCVC), in exposed humans and other species (mostly rats and mice) demonstrates function of the two metabolic pathways in vivo. The CYP pathway primarily yields chemically stable end-products. However, the GST pathway conjugate S-(1,2-dichlorovinyl)glutathione (DCVG) is further processed to multiple highly reactive species that are known to be mutagenic, especially in kidney where in situ metabolism occurs. TCE metabolism is highly variable across sexes, species, tissues and individuals. Genetic polymorphisms in several of the key enzymes metabolizing TCE and its intermediates contribute to variability in metabolic profiles and rates. In all, the evidence characterizing the complex metabolism of TCE can inform predictions of adverse responses including mutagenesis, carcinogenesis, and acute and chronic organ-specific toxicity. PMID:25484616

  2. EFFECT OF LAND TREATMENT ON THE MUTAGENICITY OF MILWAUKEE HARBOR SEDIMENT [POSTER PRESENTATION

    EPA Science Inventory

    Sediment from the Milwaukee harbor is known to be contaminated with PAHs and PCBs. A pilot-scale study was conducted to evaluate the potential of land treatment to detoxify these contaminants, as determined by several chemical and biological endpoints, including mutagenicity. T...

  3. EVALUATION OF THE MUTAGENIC ACTIVITY OF 3-NBA (3-NITROABENZANTHRONE) USING STRAINS OF SALMONELLA TYPHIMURIUM WITH DIFFERENT LEVELS OF THE ENZYMES NITROREDUCTASE AND ACETYLTRANSFERASE

    EPA Science Inventory

    The 3-NBA (3-nitro-7H- benz[d,e]antracen-7-one) is extremely potent in the Ames test an useful test for mutagenicity, being a possible inducer of tumors in animals and possible carcinogen for human beings. 3-NBA was previously identified in the exhausts of diesel, particulate mat...

  4. Low dose intoxication and a crisis of regulatory models. Chemical mutagens in the Deutsche Forschungsgemeinschaft (DFG), 1963-1973.

    PubMed

    von Schwerin, Alexander

    2010-12-01

    Regulation and the prevention of danger are among the main characteristics of the modern state. However, the idea and the conceptualization of what danger is have changed over time. The genealogy of these changes shows that the history of social change and the history of knowledge are well connected. The 1970s marked the start of a social transformation of Western industrialized societies. This article proposes that this transformation was connected with basic epistemic reconfigurations and that the genealogy of risk played a significant role. This thesis is explored through the example of DFG advisory politics. Beginning in the 1960s, the DFG expert commissions that had been established to make policy and regulation recommendations began to focus more and more on the health effects of environmental pollution. The Commission for Questions of Mutagenicity played a particularly interesting role because its recommendations resulted in the foundation of a research institution run by the DFG, the Central Laboratory for Mutagenicity Testing (CML). The challenges faced by the CML in mutagenic research and testing effected a crisis of the expert-based advisory politics of the Mutagenicity Commission and a fundamental shift in the way scientific (regulatory) knowledge was perceived and valued politically. The pattern of this crisis calls to mind the constellation of the "risk society", but as will be shown, the (re)balancing of science and politics/society presented here is more adequately understood within the framework of political epistemology.

  5. An evaluation of the mode of action framework for mutagenic carcinogens: chromium (VI)

    EPA Science Inventory

    In response to the 2005 revised U.S Environmental Protection Agency’s (EPA) Cancer Guidelines, a strategy is being developed to determine whether a carcinogen operates through a mutagenic mode of action (MOA). This information is necessary for EPA to decide whether age-dependent ...

  6. BIOASSAY-DIRECTED FRACTIONAL AND SALMONELLA MUTAGENICITY OF AUTOMOBILE AND FORKLIFT DIESEL EXHAUST PARTICLES

    EPA Science Inventory



    Abstract

    Many pulmonary toxicity studies of diesel exhaust particles (DEP) have used an
    automobile-generated sample (A-DEP) whose mutagenicity has not been reported. In contrast,
    rnany inutagenicity studies of DEP have used a forklift-generated sample (SRM ...

  7. The use of modified and non-natural nucleotides provide unique insights into pro-mutagenic replication catalyzed by polymerase eta

    PubMed Central

    Choi, Jung-Suk; Dasari, Anvesh; Hu, Peter; Benkovic, Stephen J.; Berdis, Anthony J.

    2016-01-01

    This report evaluates the pro-mutagenic behavior of 8-oxo-guanine (8-oxo-G) by quantifying the ability of high-fidelity and specialized DNA polymerases to incorporate natural and modified nucleotides opposite this lesion. Although high-fidelity DNA polymerases such as pol δ and the bacteriophage T4 DNA polymerase replicating 8-oxo-G in an error-prone manner, they display remarkably low efficiencies for TLS compared to normal DNA synthesis. In contrast, pol η shows a combination of high efficiency and low fidelity when replicating 8-oxo-G. These combined properties are consistent with a pro-mutagenic role for pol η when replicating this DNA lesion. Studies using modified nucleotide analogs show that pol η relies heavily on hydrogen-bonding interactions during translesion DNA synthesis. However, nucleobase modifications such as alkylation to the N2 position of guanine significantly increase error-prone synthesis catalyzed by pol η when replicating 8-oxo-G. Molecular modeling studies demonstrate the existence of a hydrophobic pocket in pol η that participates in the increased utilization of certain hydrophobic nucleotides. A model is proposed for enhanced pro-mutagenic replication catalyzed by pol η that couples efficient incorporation of damaged nucleotides opposite oxidized DNA lesions created by reactive oxygen species. The biological implications of this model toward increasing mutagenic events in lung cancer are discussed. PMID:26717984

  8. What’s in the Pool? A Comprehensive Identification of Disinfection By-products and Assessment of Mutagenicity of Chlorinated and Brominated Swimming Pool Water

    PubMed Central

    Richardson, Susan D.; DeMarini, David M.; Kogevinas, Manolis; Fernandez, Pilar; Marco, Esther; Lourencetti, Carolina; Ballesté, Clara; Heederik, Dick; Meliefste, Kees; McKague, A. Bruce; Marcos, Ricard; Font-Ribera, Laia; Grimalt, Joan O.; Villanueva, Cristina M.

    2010-01-01

    Background Swimming pool disinfectants and disinfection by-products (DBPs) have been linked to human health effects, including asthma and bladder cancer, but no studies have provided a comprehensive identification of DBPs in the water and related that to mutagenicity. Objectives We performed a comprehensive identification of DBPs and disinfectant species in waters from public swimming pools in Barcelona, Catalonia, Spain, that disinfect with either chlorine or bromine and we determined the mutagenicity of the waters to compare with the analytical results. Methods We used gas chromatography/mass spectrometry (GC/MS) to measure trihalomethanes in water, GC with electron capture detection for air, low- and high-resolution GC/MS to comprehensively identify DBPs, photometry to measure disinfectant species (free chlorine, monochloroamine, dichloramine, and trichloramine) in the waters, and an ion chromatography method to measure trichloramine in air. We assessed mutagenicity with the Salmonella mutagenicity assay. Results We identified > 100 DBPs, including many nitrogen-containing DBPs that were likely formed from nitrogen-containing precursors from human inputs, such as urine, sweat, and skin cells. Many DBPs were new and have not been reported previously in either swimming pool or drinking waters. Bromoform levels were greater in brominated than in chlorinated pool waters, but we also identified many brominated DBPs in the chlorinated waters. The pool waters were mutagenic at levels similar to that of drinking water (~ 1,200 revertants/L-equivalents in strain TA100–S9 mix). Conclusions This study identified many new DBPs not identified previously in swimming pool or drinking water and found that swimming pool waters are as mutagenic as typical drinking waters. PMID:20833605

  9. Evolution of the deaminase fold and multiple origins of eukaryotic editing and mutagenic nucleic acid deaminases from bacterial toxin systems

    PubMed Central

    Iyer, Lakshminarayan M.; Zhang, Dapeng; Rogozin, Igor B.; Aravind, L.

    2011-01-01

    The deaminase-like fold includes, in addition to nucleic acid/nucleotide deaminases, several catalytic domains such as the JAB domain, and others involved in nucleotide and ADP-ribose metabolism. Using sensitive sequence and structural comparison methods, we develop a comprehensive natural classification of the deaminase-like fold and show that its ancestral version was likely to operate on nucleotides or nucleic acids. Consequently, we present evidence that a specific group of JAB domains are likely to possess a DNA repair function, distinct from the previously known deubiquitinating peptidase activity. We also identified numerous previously unknown clades of nucleic acid deaminases. Using inference based on contextual information, we suggest that most of these clades are toxin domains of two distinct classes of bacterial toxin systems, namely polymorphic toxins implicated in bacterial interstrain competition and those that target distantly related cells. Genome context information suggests that these toxins might be delivered via diverse secretory systems, such as Type V, Type VI, PVC and a novel PrsW-like intramembrane peptidase-dependent mechanism. We propose that certain deaminase toxins might be deployed by diverse extracellular and intracellular pathogens as also endosymbionts as effectors targeting nucleic acids of host cells. Our analysis suggests that these toxin deaminases have been acquired by eukaryotes on several independent occasions and recruited as organellar or nucleo-cytoplasmic RNA modifiers, operating on tRNAs, mRNAs and short non-coding RNAs, and also as mutators of hyper-variable genes, viruses and selfish elements. This scenario potentially explains the origin of mutagenic AID/APOBEC-like deaminases, including novel versions from Caenorhabditis, Nematostella and diverse algae and a large class of fast-evolving fungal deaminases. These observations greatly expand the distribution of possible unidentified mutagenic processes catalyzed by

  10. Applying the erythrocyte Pig-a assay concept to rat epididymal sperm for germ cell mutagenicity evaluation.

    PubMed

    Ji, Zhiying; LeBaron, Matthew J

    2017-08-01

    The Pig-a assay, a recently developed in vivo somatic gene mutation assay, is based on the identification of mutant erythrocytes that have an altered repertoire of glycosylphosphatidylinositol (GPI)-anchored cell surface markers. We hypothesized that the erythrocyte Pig-a assay concept could be applied to rat cauda epididymal spermatozoa (sperm) for germ cell mutagenicity evaluation. We used GPI-anchored CD59 as the Pig-a mutation marker and examined the frequency of CD59-negative sperm using flow cytometry. A reconstruction experiment that spiked un-labeled sperm (mutant-mimic) into labeled sperm at specific ratios yielded good agreement between the detected and expected frequencies of mutant-mimic sperm, demonstrating the analytical ability for CD59-negative sperm detection. Furthermore, this methodology was assessed in F344/DuCrl rats administered N-ethyl-N-nitrosourea (ENU), a prototypical mutagen, or clofibrate, a lipid-lowering drug. Rats treated with 1, 10, or 20 mg/kg body weight/day (mkd) ENU via daily oral garage for five consecutive days showed a dose-dependent increase in the frequency of CD59-negative sperm on study day 63 (i.e., 58 days after the last ENU dose). This ENU dosing regimen also increased the frequency of CD59-negative erythrocytes. In rats treated with 300 mkd clofibrate via daily oral garage for consecutive 28 days, no treatment-related changes were detected in the frequency of CD59-negative sperm on study day 85 (i.e., 57 days after the last dose) or in the frequency of CD59-negative erythrocytes on study day 29. In conclusion, these data suggest that the epidiymal sperm Pig-a assay in rats is a promising method for evaluating germ cell mutagenicity. Environ. Mol. Mutagen. 58:485-493, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Chemistry and potential mutagenicity of humic substances in waters from different watersheds in Britain and Ireland

    USGS Publications Warehouse

    Watt, B.E.; Malcolm, R.L.; Hayes, M.H.B.; Clark, N.W.E.; Chipman, J.K.

    1996-01-01

    Humic substances are amorphous organic macromolecules responsible for the hue of natural waters. They are also known to be precursors of mutagens formed on chlorination prior to distribution of drinking water. In this study humic substances from the waters of primary streams, from major rivers, and from reservoirs were isolated and fractionated into humic acids (HA), fulvic acids (FA) and XAD-4 acids using columns of XAD-8 and of XAD-4 resins in tandem, and the fractions from the different sources were chlorinated and assayed for mutagenicity. CPMAS 13C NMR spectroscopy showed marked differences in compositions not only between HA, FA, and XAD-4 acids from the same water samples, but also between the same fractions from water samples from different watersheds. There were found to be strong similarities between the fractions from watersheds which had closely related soil types. Aromaticity was greatest in HAs, and lowest in XAD-4 acids, and carboxyl contents and aliphatic character were greatest in the XAD-4 acids. Carbon content decreased in the order HA > FA > XAD-4 acids, and amino acids and neutral sugars contents decreased in the order HA > XAD-4 > FA. Titration data complemented aspects of the NMR data, demonstrating that carboxyl content decreased in the order XAD-4 acids > FA > HA, and indicated that phenolic character was highest in HAs and lowest in the XAD-4 acids. All samples tested gave rise to bacterial mutagens on chlorination. Although the mutagenicities were of the same order of magnitude for the chlorinated humic samples from the different sources, the samples which showed the greatest number of revertant bacterial colonies were from the Thames and Trent, large rivers with humic materials from diverse environments, and relatively high in amino acid contents.

  12. Exposure to polycyclic aromatic hydrocarbons (PAHs), mutagenic aldehydes and particulate matter during pan frying of beefsteak.

    PubMed

    Sjaastad, Ann Kristin; Jørgensen, Rikke Bramming; Svendsen, Kristin

    2010-04-01

    Cooking with gas or electric stoves produces fumes, especially during frying, that contain a range of harmful and potentially mutagenic compounds as well as high levels of fine and ultrafine particles. The aim of this study was to see if polycyclic aromatic hydrocarbons (PAHs) and higher mutagenic aldehydes which were collected in the breathing zone of the cook, could be detected in fumes from the frying of beefsteak. The frying was performed in a model kitchen in conditions similar to those in a Western European restaurant kitchen. The levels of PAHs (16 EPA standard) and higher aldehydes (trans,trans-2,4-decadienal, 2,4-decadienal, trans-trans-2,4-nonadienal, trans-2-decenal, cis-2-decenal, trans-2-undecenal, 2-undecenal) were measured during frying on an electric or gas stove with margarine or soya bean oil as the frying fat. The number concentration of particles <100 nm in size (ultrafine) was also measured, as well as the mass concentration of total particulate matter. Levels of naphthalene were in the range of 0.15-0.27 microg/m(3) air. Measured levels of mutagenic aldehydes were between non-detectable and 61.80 microg/m(3) air. The exposure level of total aerosol was between 1.6 and 7.2 mg/m(3) air. Peak number concentrations of ultrafine particles were in the range of 6.0x10(4)-89.6x10(4) particles/cm(3) air. Naphthalene and mutagenic aldehydes were detected in most of the samples. The levels were variable, and seemed to be dependent on many factors involved in the frying process. However, according to the present results, frying on a gas stove instead of an electric stove causes increased occupational exposure to some of the components in cooking fumes which may cause adverse health effects.

  13. TOXICITY AND MUTAGENICITY OF A MIXTURE OF 25 CHEMICALS FOUND IN CONTAMINATED GROUNDWATER

    EPA Science Inventory

    A defined mixture of 25 chemicals that are often found in contaminated ground water was prepared as a water solution and studied for mutagenicity in bacteria, for prophage induction in bacteria, for palatability and effect on weight-gain in rats and mice, and for cytogenetic effe...

  14. MUTAGENICITY AND DISINFECTION BY-PRODUCTS IN SURFACE DRINKING WATER DISINFECTED WITH PERACETIC ACID

    EPA Science Inventory

    The aims of this research were to study the influence of peracetic acid (PAA) on the formation of mutagens in surface waters used for human consumption and to assess its potential application for the disinfection of drinking water. The results obtained using PAA were compared to ...

  15. DGR mutagenic transposition occurs via hypermutagenic reverse transcription primed by nicked template RNA

    PubMed Central

    Naorem, Santa S.; Han, Jin; Wang, Shufang; Lee, William R.; Heng, Xiao; Miller, Jeff F.

    2017-01-01

    Diversity-generating retroelements (DGRs) are molecular evolution machines that facilitate microbial adaptation to environmental changes. Hypervariation occurs via a mutagenic retrotransposition process from a template repeat (TR) to a variable repeat (VR) that results in adenine-to-random nucleotide conversions. Here we show that reverse transcription of the Bordetella phage DGR is primed by an adenine residue in TR RNA and is dependent on the DGR-encoded reverse transcriptase (bRT) and accessory variability determinant (Avd ), but is VR-independent. We also find that the catalytic center of bRT plays an essential role in site-specific cleavage of TR RNA for cDNA priming. Adenine-specific mutagenesis occurs during reverse transcription and does not involve dUTP incorporation, indicating it results from bRT-catalyzed misincorporation of standard deoxyribonucleotides. In vivo assays show that this hybrid RNA-cDNA molecule is required for mutagenic transposition, revealing a unique mechanism of DNA hypervariation for microbial adaptation. PMID:29109248

  16. Evaluation of an Air Quality Health Index for Predicting the Mutagenicity of Simulated Atmospheres

    EPA Science Inventory

    No study has evaluated the mutagenicity of atmospheres with a calculated air quality health index (AQHI). Thus, we generated in a UV-light-containing reaction chamber two simulated atmospheres (SAs) with similar AQHIs but different proportions of criteria pollutants and evaluated...

  17. Molecular understanding of mutagenicity using potential energy methods. Progress report, July 1, 1992--September 30, 1993

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Broyde, S.; Shapiro, R.

    1993-09-01

    Our objective has been to elucidate on a molecular level, at atomic resolution, the structures of DNAs modified by highly mutagenic aromatic amines and hydrocarbons. The underlying hypothesis is that DNA replicates with reduced fidelity when its normal right-handed B-structure is altered, and one result is a higher mutation rate. This change in structure may occur normally at a low incidence but it may be enhanced greatly after covalent modification by a mutagenic substance. The methods that we use to elucidate structures are computational, but we keep in close contact with experimental developments, and we incorporate data from NMR studiesmore » in our calculations when they are available. X-ray and low resolution spectroscopic studies have not succeeded in producing atomic resolution views of mutagen and carcinogen-oligonucleotide adducts. Even the high resolution NMR method cannot alone yield molecular views, though it does so in combination with our computations. The specific methods that we employ are minimized potential energy calculations using the torsion angle space molecular mechanics program DUPLEX to yield static views. Molecular dynamics simulations of static structures with solvent and salt can be carried out with the program AMBER; this yields mobile views in a medium that mimics aspects of the natural aqueous environment of the cell.« less

  18. Unvented kerosene-heater emissions in mobile homes: Studies on indoor air particles, semivolatile organics, carbon monoxide, and mutagenicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mumford, J.L.; Lewtas, J.; Burton, R.M.

    1990-01-01

    The study was conducted to assess human exposure to air pollutants resulting from the use of kerosene heaters in mobile homes. It has been estimated that 15-17 million unvented kerosene heaters have been sold in the United States, and 33% of these heaters have been sold to mobile home residents. The emissions from kerosene heaters can result in high pollutants levels in mobile homes that have a small air volume and low ventilation rate. Indoor air exchange rate, temperature, and humidity were measured. Chemical analyses, including polycyclic aromatic hydrocarbon (PAH) and nitro PAH, also were performed on the indoor airmore » samples from a selected home with the kerosene heater on and off. Increases in CO and organic concentrations resulting from the use of kerosene heaters were found in most homes monitored. Chemical analysis data also suggested the presence of evaporated, unburned kerosene fuel present in semivolatile organics collected in the XAD samples. When kerosene heaters were on, 56% of the sampling days (in all homes) showed dose-response mutagenic activity and 19% showed mutagenic activity on the heater-off days. In comparison with the U.S. national ambient air standards, four out of the eight heaters investigated in this study emitted pollutants that exceeded the ambient air standards some days. These data suggested that emissions from unvented kerosene heaters can significantly impact indoor air quality in mobile homes and that these emissions contain carcinogenic compounds and can be potentially carcinogenic in humans.« less

  19. INFLUENCE OF CHEMICAL AND PHYSICAL MUTAGENIC FACTORS ON THE VIRUS of tick-BORNE ENCEPHALITIS

    DTIC Science & Technology

    In experiments the chemicals azouridine, azouracil, 5-bromuracil, formaldehyde, urethan and proflavine were used as mutagenic agents. The influence of...with passaging (tests with proflavine ). Subject to further study is the problem of the reversibility of these properties, and also the fixing of

  20. The use of modified and non-natural nucleotides provide unique insights into pro-mutagenic replication catalyzed by polymerase eta.

    PubMed

    Choi, Jung-Suk; Dasari, Anvesh; Hu, Peter; Benkovic, Stephen J; Berdis, Anthony J

    2016-02-18

    This report evaluates the pro-mutagenic behavior of 8-oxo-guanine (8-oxo-G) by quantifying the ability of high-fidelity and specialized DNA polymerases to incorporate natural and modified nucleotides opposite this lesion. Although high-fidelity DNA polymerases such as pol δ and the bacteriophage T4 DNA polymerase replicating 8-oxo-G in an error-prone manner, they display remarkably low efficiencies for TLS compared to normal DNA synthesis. In contrast, pol η shows a combination of high efficiency and low fidelity when replicating 8-oxo-G. These combined properties are consistent with a pro-mutagenic role for pol η when replicating this DNA lesion. Studies using modified nucleotide analogs show that pol η relies heavily on hydrogen-bonding interactions during translesion DNA synthesis. However, nucleobase modifications such as alkylation to the N2 position of guanine significantly increase error-prone synthesis catalyzed by pol η when replicating 8-oxo-G. Molecular modeling studies demonstrate the existence of a hydrophobic pocket in pol η that participates in the increased utilization of certain hydrophobic nucleotides. A model is proposed for enhanced pro-mutagenic replication catalyzed by pol η that couples efficient incorporation of damaged nucleotides opposite oxidized DNA lesions created by reactive oxygen species. The biological implications of this model toward increasing mutagenic events in lung cancer are discussed. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells

    PubMed Central

    Weng, Mao-wen; Hu, Yu; Chen, Wei-sheng; Chou, David; Liu, Yan; Donin, Nicholas; Huang, William C.; Lepor, Herbert; Wu, Xue-Ru; Wang, Hailin; Beland, Frederick A.; Tang, Moon-shong

    2014-01-01

    Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants, can cause bladder tumor in rat models. Their role in TS related BC has not been forthcoming. To establish the relationship between acrolein and 4-ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT), and measured their mutagenicity in human urothelial cells. We found that the acrolein-dG levels in NHUM and BTT are 10-30 fold higher than 4-ABP-DNA adduct levels and that the acrolein-dG levels in BTT are 2 fold higher than in NHUM. Both acrolein-dG and 4-ABP-DNA adducts are mutagenic; however, the former are 5 fold more mutagenic than the latter. These two types of DNA adducts induce different mutational signatures and spectra. We found that acrolein inhibits nucleotide excision and base excision repair and induces repair protein degradation in urothelial cells. Since acrolein is abundant in TS, inhaled acrolein is excreted into urine and accumulates in the bladder and because acrolein inhibits DNA repair and acrolein-dG DNA adducts are mutagenic, we propose that acrolein is a major bladder carcinogen in TS. PMID:24939871

  2. Topology of evolving, mutagenized viral populations: quasispecies expansion, compression, and operation of negative selection.

    PubMed

    Ojosnegros, Samuel; Agudo, Rubén; Sierra, Macarena; Briones, Carlos; Sierra, Saleta; González-López, Claudia; Domingo, Esteban; Cristina, Juan

    2008-07-17

    The molecular events and evolutionary forces underlying lethal mutagenesis of virus (or virus extinction through an excess of mutations) are not well understood. Here we apply for the first time phylogenetic methods and Partition Analysis of Quasispecies (PAQ) to monitor genetic distances and intra-population structures of mutant spectra of foot-and-mouth disease virus (FMDV) quasispecies subjected to mutagenesis by base and nucleoside analogues. Phylogenetic and PAQ analyses have revealed a highly dynamic variation of intrapopulation diversity of FMDV quasispecies. The population diversity first suffers striking expansions in the presence of mutagens and then compressions either when the presence of the mutagenic analogue was discontinued or when a mutation that decreased sensitivity to a mutagen was selected. The pattern of mutations found in the populations was in agreement with the behavior of the corresponding nucleotide analogues with FMDV in vitro. Mutations accumulated at preferred genomic sites, and dn/ds ratios indicate the operation of negative (or purifying) selection in populations subjected to mutagenesis. No evidence of unusually elevated genetic distances has been obtained for FMDV populations approaching extinction. Phylogenetic and PAQ analysis provide adequate procedures to describe the evolution of viral sequences subjected to lethal mutagenesis. These methods define the changes of intra-population structure more precisely than mutation frequencies and Shannon entropies. PAQ is very sensitive to variations of intrapopulation genetic distances. Strong negative (or purifying) selection operates in FMDV populations subjected to enhanced mutagenesis. The quantifications provide evidence that extinction does not imply unusual increases of intrapopulation complexity, in support of the lethal defection model of virus extinction.

  3. An evaluation of the mode of action framework for mutagenic carcinogens: Chromium (VI): SOT.

    EPA Science Inventory

    In response to the 2005 revised U.S Environmental Protection Agency’s (EPA) Cancer Guidelines, a strategy is being developed to determine whether a carcinogen operates through a mutagenic mode of action (MOA). This information is necessary for EPA to decide whether age-dependent ...

  4. Determination of the mutagenic and genotoxic potential of simulated leachate from an automobile workshop soil on eukaryotic system.

    PubMed

    Alabi, Okunola Adenrele; Omosebi, Omotoyosi; Chizea, Ifychukwwu

    2015-07-01

    Contamination of soil and water bodies with spent engine oil and petroleum products is a serious ecological problem, primarily in the automobile workshops and garages. This has potential short and chronic adverse health risks. Information is currently scarce on the potential mutagenicity and genotoxicity of such wastes. In this study, the potential mutagenic and genotoxic effects of simulated leachate from automobile workshop soil in Sagamu, Ogun state, Nigeria, were investigated. The assays utilized were bone marrow micronucleus (MN) and chromosome aberration (CA), sperm morphology and sperm count in mice. The physicochemical analysis of the leachate was also carried out. Experiments were carried out at concentrations of 1, 5, 10, 25, 50, 75 and 100% (volume per volume; leachate:distilled water) of the leachate sample. MN analysis showed a concentration-dependent induction of micronucleated polychromatic erythrocytes across the treatment groups. In the CA test, there was concentration-dependent significant reduction in mitotic index and induction of different types of CAs. Assessment of sperm shape showed a significant increase in sperm abnormalities with significant decrease in mean sperm count in treated groups. Heavy metals analyzed in the tested sample are believed to contribute significantly to the observed genetic damage. This indicates that automobile workshop soil-simulated leachate contains potential genotoxic agents and constitutes a genetic risk in exposed human population. © The Author(s) 2013.

  5. Approach for detecting mutagenicity of biodegraded and ozonated pharmaceuticals, metabolites and transformation products from a drinking water perspective.

    PubMed

    Gartiser, Stefan; Hafner, Christoph; Kronenberger-Schäfer, Kerstin; Happel, Oliver; Trautwein, Christoph; Kümmerer, Klaus

    2012-09-01

    Many pharmaceuticals and related metabolites are not efficiently removed in sewage treatment plants and enter into surface water. There, they might be subject of drinking water abstraction and treatment by ozonation. In this study, a systematic approach for producing and effect-based testing of transformation products (TPs) during the drinking water ozonation process is proposed. For this, two pharmaceutical parent substances, three metabolites and one environmental degradation product were investigated with respect to their biodegradability and fate during drinking water ozonation. The Ames test (TA98, TA100) was used for the identification of mutagenic activity present in the solutions after testing inherent biodegradability and/or after ozonation of the samples. Suspicious results were complemented with the umu test. Due to the low substrate concentration required for ozonation, all ozonated samples were concentrated via solid phase extraction (SPE) before performing the Ames test. With the exception of piracetam, all substances were only incompletely biodegradable, suggesting the formation of stable TPs. Metformin, piracetam and guanylurea could not be removed completely by the ozonation process. We received some evidence that technical TPs are formed by ozonation of metformin and piracetam, whereas all tested metabolites were not detectable by analytical means after ozonation. In the case of guanylurea, one ozonation TP was identified by LC/MS. None of the experiments showed an increase of mutagenic effects in the Ames test. However, the SPE concentration procedure might lead to false-positive results due to the generation of mutagenic artefacts or might lead to false-negative results by missing adequate recovery efficiency. Thus, these investigations should always be accompanied by process blank controls that are carried out along the whole ozonation and SPE procedure. The study presented here is a first attempt to investigate the significance of

  6. Recent meteor observing activities in Japan

    NASA Astrophysics Data System (ADS)

    Yamamoto, M.

    2005-02-01

    The meteor train observation (METRO) campaign is described as an example of recent meteor observing activity in Japan. Other topics of meteor observing activities in Japan, including Ham-band radio meteor observation, the ``Japan Fireball Network'', the automatic video-capture software ``UFOCapture'', and the Astro-classroom programme are also briefly introduced.

  7. SOS gene induction and possible mutagenic effects of freeze-drying in Escherichia coli and Salmonella typhimurium.

    PubMed

    Rosen, Rachel; Buchinger, Sebastian; Pfänder, Ramona; Pedhazur, Rami; Reifferscheid, Georg; Belkin, Shimshon

    2016-11-01

    We report the results of a study of the potential negative effects of the freeze-drying process, normally considered a benign means for long-term conservation of living cells and the golden standard in bacterial preservation. By monitoring gene induction using a whole-cell Escherichia coli bioreporter panel, in which diverse stress-responsive gene promoters are fused to luminescent or fluorescent reporting systems, we have demonstrated that DNA repair genes belonging to the SOS operon (recA, sulA, uvrA, umuD, and lexA) were induced upon resuscitation from the freeze-dried state, whereas other stress-responsive promoters such as grpE, katG, phoA, soxS, and sodA were not affected. This observation was confirmed by the UMU-chromotest (activation of the umuD gene promoter) in Salmonella typhimurium, as well as by real-time PCR analyses of selected E. coli SOS genes. We further show that a functional SOS operon is important in viability maintenance following resuscitation, but that at the same time, this repair system may introduce significantly higher mutation rates, comparable to those induced by high concentrations of a known mutagen. Our results also indicate that the entire freeze-drying process, rather than either freezing or drying separately, is instrumental in the induction of DNA damage.

  8. Quantification of a potent mutagenic 4-amino-3,3'-dichloro-5,4'-dinitrobiphenyl (ADDB) and the related chemicals in water from the Waka River in Wakayama, Japan.

    PubMed

    Mizuno, Tomoko; Takamura-Enya, Takeji; Watanabe, Tetsushi; Hasei, Tomohiro; Wakabayashi, Keiji; Ohe, Takeshi

    2007-06-15

    4-Amino-3,3'-dichloro-5,4'-dinitrobiphenyl (ADDB) is a novel chemical exerting strong mutagenicity, especially in the absence of metabolic activation. In addition to mutagenicity, ADDB may also disrupt the endocrine system in vitro. ADDB may be discharged from chemical plants near the Waka River and could be unintentionally formed via post-emission modification of drainage water containing 3,3'-dichlorobenzidine (DCB), which is a precursor in the manufacture of polymers and dye intermediates in chemical plants. The main purpose of this study was to make a comprehensive survey of the behaviour and levels of ADDB and suspected starting material or intermediates of ADDB, i.e., DCB, 3,3'-dichloro-4,4'-dinitrobiphenyl (DDB), and 4-amino-3,3'-dichloro-4'-nitrobipheny (ADNB) in Waka River water samples. We also postulated the formation pathway of ADDB. Water samples were collected at five sampling sites from the Waka River four times between March 2003 and December 2004. Samples were passed through Supelpak2 columns, and adsorbed materials were then extracted with methanol. Extracts were used for quantification of ADDB and the related chemicals by HPLC on reverse-phase columns; mutagenicity was evaluated in the Salmonella assay using the O-acetyltransferase-overexpressing strain YG1024. High levels of ADDB, DCB, DDB, and ADNB (12.0, 20,400, 134.8, and 149.4ng/L-equivalent) were detected in the samples collected at the site where wastewater was discharged from chemical plants into the river. These water samples also showed stronger mutagenicity in YG1024 both with and without S9 mix than the other water samples collected from upstream and downstream sites. The results suggest that ADDB is unintentionally formed from DCB via ADNB in the process of wastewater treatment of drainage water containing DCB from chemical plants.

  9. Interstitial telomeric sequences in human chromosomes cluster with common fragile sites, mutagen sensitive sites, viral integration sites, cancer breakpoints, proto-oncogenes and breakpoints involved in primate evolution

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Adekunle, S.S.A.; Wyandt, H.; Mark, H.F.L.

    1994-09-01

    Recently we mapped the telomeric repeat sequences to 111 interstitial sites in the human genome and to sites of gaps and breaks induced by aphidicolin and sister chromatid exchange sites detected by BrdU. Many of these sites correspond to conserved fragile sites in man, gorilla and chimpazee, to sites of conserved sister chromatid exchange in the mammalian X chromosome, to mutagenic sensitive sites, mapped locations of proto-oncogenes, breakpoints implicated in primate evolution and to breakpoints indicated as the sole anomaly in neoplasia. This observation prompted us to investigate if the interstitial telomeric sites cluster with these sites. An extensive literaturemore » search was carried out to find all the available published sites mentioned above. For comparison, we also carried out a statistical analysis of the clustering of the sites of the telomeric repeats with the gene locations where only nucleotide mutations have been observed as the only chromosomal abnormality. Our results indicate that the telomeric repeats cluster most with fragile sites, mutagenic sensitive sites and breakpoints implicated in primate evolution and least with cancer breakpoints, mapped locations of proto-oncogenes and other genes with nucleotide mutations.« less

  10. SYNTHESIS, MUTAGENICITY, CELL TRANSFORMATION, AND IN VITRO METABOLISM OF NAPHTHO[1,2-E]PYRENE

    EPA Science Inventory

    Synthesis, mutagenicity, cell transformation, and in vitro metabolism of naphtho[ I ,2-e ]pyrene

    Relatively, little attention has been given to C24HJ4- PAH; in part due to the lack of established methods for the synthesis of all possible isomers. Among the naphthopyrene (...

  11. Legal implications of monitoring workers for carcinogenic and mutagenic risk.

    PubMed

    Damme, C J

    1982-01-01

    Many industries have initiated testing programs designed to identify workers who are especially vulnerable to workplace assaults by carcinogenic or mutagenic agents. This paper examines a number of legal issues attendant on such programs, including disclosure and consent, confidentiality, and other potential liability-producing factors. This paper also briefly looks at the legal issues that might arise if the federal government were to mandate similar programs. Finally, the basic rationale of industrial monitoring programs is discussed within the context of the emerging legal issues.

  12. Carcinogens, Teratogens and Mutagens: Their Impact on Occupational Health, Particularly for Women in Veterinary Medicine.

    ERIC Educational Resources Information Center

    Milligan, J. E.; And Others

    1983-01-01

    Pregnant women, especially those working in veterinary medicine, face occupational health/disease risks from mutagens, teratogens, and carcinogens. These hazards can be placed into three categories: physical, chemical, and biological. Each of these hazards is discussed with examples. (Author/JN)

  13. Quantitative changes in endogenous DNA adducts correlate with conazole mutagenicity and tumorigenicity in mouse liver.**

    EPA Science Inventory

    We have previously shown that the conazole fungicides triadimefon and propiconazole, which are tumorigenic in mouse liver, are in vivo mouse liver mutagens in the Big Blue" transgenic mutation assay when administered in feed at tumorigenic doses. The nontumorigenic conazole myclo...

  14. Quantitative changes in endogenous DNA adducts correlate with conazole mutagenicity and tumorigenicity in mouse liver.

    EPA Science Inventory

    We have previously shown that the conazole fungicides triadimefon and propiconazole, which are tumorigenic in mouse liver, are in vivo mouse liver mutagens in the Big Blue" transgenic mutation assay when administered in feed at tumorigenic doses. The nontumorigenic conazole myclo...

  15. Improved mutagen testing systems in mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Roderick, T.H.

    Our laboratory was the first to induce and ascertain a mammalian chromosomal inversion; we did this by searching for a high frequency of first meiotic anaphase bridges in testes of males whose fathers received post-spermatogonial radiation or mutagenesis from chromosomal breaking chemical mutagens. One test in was examined in each mouse, and those showing a high frequency were then mated to determine if the high frequency were passed on as a dominant and whether linkage analysis suggested the presence of an inversion. A very high incidence (exceeding 20% bridges in first meiotic anaphase bridges) was found in about 1 inmore » 150 males examined and this frequency was generally found to be passed on to the offspring an predicted. Later cytological banding techniques were developed elsewhere and we used them to show visually the inverted orders of the inverted chromosomal segments. Since that time we have induced inversions covering most of the mouse genome.« less

  16. Genetic tests in mice of caffeine alone and in combination with mutagens

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Thayer, P.S.; Kensler, C.J.

    1973-06-01

    The possible mutagenicity of caffeine was studied in mice by the dominant-lethal method, in three experiments. Male mice were given caffeine in drinking water for 8 weeks at 3.6, 13.4, 49, and 122 mg/kg/day (comparable to human consumption of 2.8 to 95 cups of coffee per day). Subsequent mating of each of six males from each group to five females per week for 8 weeks showed no significant increase in dominant-lethal mutations (embryonic deaths) whether expressed as early deaths per pregnant female or as mutation index. Although males consuming the two higher levels of caffeine produced fewer pregnancies, litter sizesmore » of females giving birth were not reduced. Single ip injections of caffeine (15 mg/kg) were given to groups of male mice prior to, subsequent to, and immediately at the time of receiving x-rays (100 R). Each of five males from each group was mated to five females per week for 7 weeks. Embryonic deaths did not show any enhancing effect of caffeine on the mutagenicity produced by the irradiation. Three groups of male mice ingested caffeine in water for 16 weeks at levels of 0, 4, and 13 mg/kg/day. Subgroups of five from each group were given either: no further treatment, a single dose of triethylene melamine at 0.2 mg/kg, or 100 R of x ray, and mated for 7 weeks as above. Fertility and litter size were not affected by the caffeine pretreatment, nor did it modify the induction of dominant-lethal mutations by triethylene melamine or x rays. Litter sizes showed no significant preimplantation losses in any experiment. Thus, under the conditions described herein and at the doses employed (higher than human exposure), there was no evidence for the mutagenicity of caffeine or the inhibition of DNA repair mechanisms in these mammalian systems. (auth)« less

  17. Quantitative assessment of groundwater quality using a biological indicator: some preliminary observations.

    PubMed

    Pfeil, R M; Venkat, J A; Plimmer, J R; Sham, S; Davis, K; Nair, P P

    1994-02-01

    The genotoxicity of groundwater was evaluated, using a novel application of the SOS microplate assay (SOSMA). Organic residues were extracted from groundwater samples from Maryland, Pennsylvania, and Delaware by using C-18 bonded silica solid phase extraction tubes. Total organic carbon content (TOC) of water samples was also determined. The genotoxicity of the extracts was determined by the SOSMA. Relative activity (RA) as determined by the SOSMA is a quantitative measure of genotoxicity based on a comparison to the activity of the mutagen, 4-nitroquinoline oxide. Low levels of RA (about 2x background) were detected in waters from sites within these states. There was considerable temporal and spatial variation in the observed RA, but no definite patterns were observed in the variation. Between sampling sites there was a positive correlation between RA and TOC; however, this relationship appeared to be reversed occasionally within a sampling site. The extraction and bioassay methods provide an easy and relatively inexpensive means of determining water quality.

  18. Naked eye detection of mutagenic DNA photodimers using gold nanoparticles.

    PubMed

    Kim, Joong Hyun; Chung, Bong Hyun

    2011-01-15

    We developed a method to detect mutagenic DNA photodimers by the naked eye using gold nanoparticles. The stability of gold nanoparticles in a high ionic strength solution is maintained by straight ssDNA adsorbed physically on the AuNPs. However, we found that UV-irradiated DNA was less adsorptive onto gold nanoparticles because of a conformational change of UV-irradiated DNA. The accumulated deformation of the DNA structure by multiple-dimer formation triggered aggregation of the gold nanoparticles mixed with the UV-irradiated DNA and thus red to purple color changes of the mixture, which allowed colorimetric detection of the DNA photodimers by the naked eye. No fragmented mass and reactive oxygen species production under the UVB irradiation confirmed that the aggregation of gold nanoparticles was solely attributed to the accumulated deformation of the UV irradiated DNA. The degree of gold nanoparticles-aggregation was dependent on the UVB irradiated time and base compositions of the UV-irradiated oligonucleotides. In addition, we successfully demonstrated how to visually qualify the photosensitizing effect of chemical compounds in parallel within only 10 min by applying this new method. Since our method does not require any chemical or biochemical treatments or special instruments for purifying and qualifying the DNA photolesions, it should provide a feasible tool for the studies of the UV-induced mutagenic or carcinogenic DNA dimers and accelerate screening of a large number of drug candidates. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  19. Persistent damaged bases in DNA allow mutagenic break repair in Escherichia coli

    PubMed Central

    Moore, Jessica M.; Correa, Raul; Rosenberg, Susan M.

    2017-01-01

    Bacteria, yeast and human cancer cells possess mechanisms of mutagenesis upregulated by stress responses. Stress-inducible mutagenesis potentially accelerates adaptation, and may provide important models for mutagenesis that drives cancers, host pathogen interactions, antibiotic resistance and possibly much of evolution generally. In Escherichia coli repair of double-strand breaks (DSBs) becomes mutagenic, using low-fidelity DNA polymerases under the control of the SOS DNA-damage response and RpoS general stress response, which upregulate and allow the action of error-prone DNA polymerases IV (DinB), II and V to make mutations during repair. Pol IV is implied to compete with and replace high-fidelity DNA polymerases at the DSB-repair replisome, causing mutagenesis. We report that up-regulated Pol IV is not sufficient for mutagenic break repair (MBR); damaged bases in the DNA are also required, and that in starvation-stressed cells, these are caused by reactive-oxygen species (ROS). First, MBR is reduced by either ROS-scavenging agents or constitutive activation of oxidative-damage responses, both of which reduce cellular ROS levels. The ROS promote MBR other than by causing DSBs, saturating mismatch repair, oxidizing proteins, or inducing the SOS response or the general stress response. We find that ROS drive MBR through oxidized guanines (8-oxo-dG) in DNA, in that overproduction of a glycosylase that removes 8-oxo-dG from DNA prevents MBR. Further, other damaged DNA bases can substitute for 8-oxo-dG because ROS-scavenged cells resume MBR if either DNA pyrimidine dimers or alkylated bases are induced. We hypothesize that damaged bases in DNA pause the replisome and allow the critical switch from high fidelity to error-prone DNA polymerases in the DSB-repair replisome, thus allowing MBR. The data imply that in addition to the indirect stress-response controlled switch to MBR, a direct cis-acting switch to MBR occurs independently of DNA breakage, caused by ROS

  20. Persistent damaged bases in DNA allow mutagenic break repair in Escherichia coli.

    PubMed

    Moore, Jessica M; Correa, Raul; Rosenberg, Susan M; Hastings, P J

    2017-07-01

    Bacteria, yeast and human cancer cells possess mechanisms of mutagenesis upregulated by stress responses. Stress-inducible mutagenesis potentially accelerates adaptation, and may provide important models for mutagenesis that drives cancers, host pathogen interactions, antibiotic resistance and possibly much of evolution generally. In Escherichia coli repair of double-strand breaks (DSBs) becomes mutagenic, using low-fidelity DNA polymerases under the control of the SOS DNA-damage response and RpoS general stress response, which upregulate and allow the action of error-prone DNA polymerases IV (DinB), II and V to make mutations during repair. Pol IV is implied to compete with and replace high-fidelity DNA polymerases at the DSB-repair replisome, causing mutagenesis. We report that up-regulated Pol IV is not sufficient for mutagenic break repair (MBR); damaged bases in the DNA are also required, and that in starvation-stressed cells, these are caused by reactive-oxygen species (ROS). First, MBR is reduced by either ROS-scavenging agents or constitutive activation of oxidative-damage responses, both of which reduce cellular ROS levels. The ROS promote MBR other than by causing DSBs, saturating mismatch repair, oxidizing proteins, or inducing the SOS response or the general stress response. We find that ROS drive MBR through oxidized guanines (8-oxo-dG) in DNA, in that overproduction of a glycosylase that removes 8-oxo-dG from DNA prevents MBR. Further, other damaged DNA bases can substitute for 8-oxo-dG because ROS-scavenged cells resume MBR if either DNA pyrimidine dimers or alkylated bases are induced. We hypothesize that damaged bases in DNA pause the replisome and allow the critical switch from high fidelity to error-prone DNA polymerases in the DSB-repair replisome, thus allowing MBR. The data imply that in addition to the indirect stress-response controlled switch to MBR, a direct cis-acting switch to MBR occurs independently of DNA breakage, caused by ROS