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1.
D.B. McGregor G. Cruzan R.D. Callander K. May M. Banton 《Mutation Research - Genetic Toxicology and Environmental Mutagenesis》2005,565(2):265
Tertiary-Butyl alcohol (TBA), tertiary-butyl acetate™ (TBAc™) and methyl tertiary-butyl ether (MTBE) are chemicals to which the general public may be exposed either directly or as a result of their metabolism. There is little evidence that they are genotoxic; however, an earlier publication reported that significant results were obtained in Salmonella typhimurium TA102 mutagenicity tests with both TBA and MTBE. We now present results of testing these chemicals and TBAc™ against S. typhimurium strains in two laboratories. The emphasis was placed on testing with S. typhimurium TA102 and the use of both dimethyl sulphoxide and water as vehicles. Dose levels up to 5000 μg/plate were used and incubations were conducted in both the presence and absence of liver S9 prepared from male rats treated with either Arochlor 1254 or phenobarbital-β-naphthoflavone. The experiments were replicated, but in none of them was a significant mutagenic response observed, thus the current evidence indicates the TBA, TBAc™ and MTBE are not mutagenic in bacteria. 相似文献
2.
Williams-Hill D Spears CP Prakash S Olah GA Shamma T Moin T Kim LY Hill CK 《Mutation research》1999,446(1):15-21
Methyl-tert-butylether (MTBE) is an oxygenate widely used in the United States as a motor vehicle fuel additive to reduce emissions and as an octane booster [National Research Council, Toxicological and Performance Aspects of Oxygenated Motor Vehicle Fules, National Academy Press, Washington, DC, 1996]. But it is the potential for MTBE to enter drinking water supplies that has become an area of public concern. MTBE has been shown to induce liver and kidney tumors in rodents but the biochemical process leading to carcinogenesis is unknown. MTBE was previously shown to be non-mutagenic in the standard Ames plate incorporation test with tester strains that detect frame shift (TA98) and point mutations (TA100) and in a suspension assay using TA104, a strain that detects oxidative damage, suggesting a non-genotoxic mechanism accounts for its carcinogenic potential. These strains are deficient in excision repair due to deletion of the uvrB gene. We hypothesized that the carcinogenic activity of MTBE may be dependent upon a functional excision repair system that attempts to remove alkyl adducts and/or oxidative base damage caused by direct interaction of MTBE with DNA or by its metabolites, formaldehyde and tert-butyl alcohol (TBA), established carcinogens that are mutagenic in some Ames strains. To test our hypothesis, the genotoxicity of MTBE-induced DNA alterations was assayed using the standard Ames test with TA102, a strain similar to TA104 in the damage it detects but uvrB + and, therefore, excision repair proficient. The assay was performed (1) with and without Aroclor-induced rat S-9, (2) with and without the addition of formaldehyde dehydrogenase (FDH), and (3) with human S-9 homogenate. MTBE was weakly mutagenic when tested directly and moderately mutagenic with S-9 activation producing between 80 and 200 TA102 revertants/mg of compound. Mutagenicity was inhibited 25%-30% by FDH. TA102 revertants were also induced by TBA and by MTBE when human S-9 was substituted for rat S-9. We conclude that MTBE and its metabolites induce a mutagenic pathway involving oxidation of DNA bases and an intact repair system. These data are significant in view of the controversy surrounding public safety and the environmental release of MTBE and similar fuel additives. 相似文献
3.
Strain TA102 of S. typhimurium is a new histidine-requiring mutant, particularly suited to the detection of oxidative mutagens acting at A.T base pairs. 10 oxidizing chemicals, previously tested in strain TA102, were used to evaluate the mutagenic sensitivity of the L-arabinose forward mutation assay of S. typhimurium with respect to those types of mutagens. The mutagenicity of each compound was determined by liquid test, measuring both the frequency of mutants among the survivors and the absolute number of mutants growing in selective plates with traces of D-glucose. Strain BA13 with a wild-type lipopolysaccharide barrier was used as compared to the deep rough derivative strain BA9. The chemicals studied were: bleomycin, t-butyl hydroperoxide, chromium trioxide, cumene hydroperoxide, formaldehyde, glyoxal, glutaraldehyde, hydrogen peroxide, paraquat, and phenylhydrazine. Additionally, ultrasonic oscillation was used as a presumable non-mutagenic lethal control treatment. The L-arabinose forward mutation assay detected the mutagenic activity of all the chemicals under study with a high degree of sensitivity, including paraquat which is unable to revert strain TA102. Positive responses were obtained at doses equivalent to or 10 times lower than the doses detected by strain TA102. The results support the idea that the L-arabinose forward mutation assay could replace the set of specific tester strains used by the histidine reverse mutation assay in general screening for genetic toxins. 相似文献
4.
Mutagenicity of products formed by ozonation of naphthoresorcinol in aqueous solutions 总被引:2,自引:0,他引:2
The mutagenicity of products formed by ozonation of naphthoresorcinol in aqueous solution was assayed with Salmonella typhimurium strains TA97, TA98, TA100, TA102 and TA104 in the presence and absence of S9 mix from phenobarbital- and 5,6-benzoflavone-induced rat liver. Ozonated naphthoresorcinol was mutagenic in TA97, TA98, TA100 and TA104 without S9 mix. By the addition of S9 mix, the mutagenic activity of ozonated naphthoresorcinol was markedly suppressed in TA98 and TA100, but became positive in TA102. High-performance liquid chromatography (HPLC) after derivatization to 2,4-dinitrophenylhydrazones demonstrated the formation of glyoxal as an ozonation product of naphthoresorcinol. Ion chromatographic technique also demonstrated the formation of o-phthalic acid, muconic acid, maleic acid, mesoxalic acid, glyoxylic acid and oxalic acid as ozonation products. The mutagenicity assays of these identified products with five Salmonella showed that glyoxal and glyoxylic acid were directly mutagenic; the former in TA100, TA102 and TA104, the latter in TA97, TA100 and TA104. In the presence of S9 mix, glyoxylic acid gave a positive response of mutagenicity for TA102. The experimental evidence supported that glyoxal and glyoxylic acid may contribute to the mutagenicity of ozonated naphthoresorcinol. 相似文献
5.
The mutagenic effects of bithionol sulfoxide and its two major metabolites, bithionol and bithionol sulfone, on 4 Salmonella typhimurium strains (TA97, TA98, TA100 and TA102) were investigated. Bithionol sulfoxide was found to be mutagenic to TA98 and TA100. However, mutagenicity was abolished in the presence of rat-liver S9 fractions. 相似文献
6.
There is concern at present that treatment with histamine H2-receptor antagonists might promote the development of gastric cancer by producing conditions which favour intragastric formation of N-nitroso compounds. If H2-receptor antagonist therapy causes increased intragastric levels of N-nitroso compounds, an issue not yet resolved by analytical studies, corresponding changes in the mutagenic activity of gastric juice might be anticipated. In this study mutagenic activity and pH were measured in fasting gastric aspirate from 18 peptic ulcer patients before and during the final week of therapy with ranitidine (n = 10) or cimetidine (n = 8). Mutagenic activity was assessed using Salmonella typhimurium TA98 and TA100 in a modified pre-incubation "fluctuation" test. No significant change in mutagenic activity was detected after therapy. Of 15 patients found to have significant mutagenic activity in their fasting gastric juice before treatment, 14 remained mutagenic following treatment. Mutation frequencies (sum of positive wells in duplicate 96-well microtitre plates, mean +/- SD) for TA98 and TA100 were respectively, 20 +/- 34 and 100 +/- 64 before compared with 10 +/- 6 and 102 +/- 65 after therapy (p greater than 0.05). Changes in mutagenic activity were similar in both treatment groups and unrelated to duration of therapy, changes in gastric pH or ulcer healing. In vitro, neither cimetidine in aqueous solution, nor gastric juice preincubated with cimetidine showed significant mutagenic activity. These results provide no evidence that increased intragastric levels of genotoxic chemicals, such as N-nitroso compounds, occur during H2-receptor antagonist therapy. 相似文献
7.
The genotoxic potential of bidi tobacco was evaluated by mutagenicity testing of aqueous, aqueous: ethanolic, ethanolic and chloroform extracts of processed tobacco used in the manufacture of 'bidis', indigenous forms of cigarettes smoked in India. The Salmonella/mammalian microsome test (Ames assay) was used to detect mutagenicity in tester strains TA98, TA100 and TA102. The extracts were tested in the absence and presence of metabolic activation using liver S9 from rat and hamster, and following in vitro nitrosation with sodium nitrite at acidic pH. All the extracts were non-mutagenic in the absence of nitrosation. The nitrosated aqueous extract was mutagenic in strains TA98 and TA100. While weak mutagenicity was elicited by the nitrosated aqueous: ethanolic extract in TA100, the nitrosated ethanolic extract induced a 3-fold increase in the number of revertants in the same strain. Moreover both these extracts elicited a strong mutagenic response in TA102, while the chloroform extract was non-mutagenic even after nitrite treatment. The present study indicates that workers employed in the bidi industry are exposed to potentially mutagenic and genotoxic chemicals in the course of their occupation. 相似文献
8.
S Vasilieva B Tanirbergenov S Abilev G Migatchev M T Huttunen 《Mutation research》1990,244(4):321-329
A total of 23 chemicals--biphenyls, phenanthrenequinones and fluorenones--were tested for mutagenicity towards Salmonella typhimurium strains TA1538, TA1535 and TA98. SOS-inducing activity of the same chemicals was studied in terms of the SOS-inducing potency in Escherichia coli PQ37, using an automated instrument controlled by a dedicated computer program for the SOS Chromotest. Of the 23 chemicals studied 14 induced His+ revertants in S. typhimurium TA1538 hisD305 (-1 frameshift); none induced His+ reversions in TA1535 (base-pair substitution). The mutagenicity of the chemicals in S. typhimurium TA98 (pKM 101) was lower than in TA1538. There was a close correlation between mutagenicity and SOS-inducing activity of fluorenones and phenanthrenequinones. None of the biphenyls tested induced SOS response and this property does not depend upon the mutagenic activity of the chemicals. SOS Chromotest is particularly valid in detecting chemicals which give rise to base-pair substitutions through SOS induction. If positive results are obtained, the Salmonella assay may be omitted. However, this test cannot replace the Ames test especially for the primary screening of mutagenicity of chemicals with unknown structure. 相似文献
9.
The mutagenic and genotoxic effects of two methylxanthines, theophylline (TH) and theobromine (TB), were assessed in the Ames mutagenicity assay (in strains TA97a, TA100, TA102 and TA104) and in vivo sister chromatid exchanges (SCEs) in bone marrow cells of mice. These are the two most commonly used nervous system stimulators throughout the world. TH is used in the long-term treatment of asthma. Bacterial mutagenicity assay showed very weak mutagenic effects of both drugs in Salmonella strains TA102 and TA104 only in certain concentrations when S9 was added to it. No mutagenic effects were observed in any other strains used in this assay either with or without metabolic activation. But results of in vivo SCE assay indicate that these two drugs can induce significant SCE in bone marrow cells of mice. 相似文献
10.
The drug antipyrine and its 4-substituted analogs, 4-aminoantipyrine, 4-dimethylaminoantipyrine (aminopyrine) and 4-nitrosoantipyrine were tested for mutagenicity against the screening array of Salmonella typhimurium tester strains TA100, TA98, TA97, TA102 and TA104. Antipyrine and aminopyrine were nonmutagenic to all 5 tester strains even in the presence of S9. 4-Aminoantipyrine was directly mutagenic to TA97 only and the presence of S9 slightly increased its activity. 4-Nitrosoantipyrine was directly mutagenic to all tester strains used and S9 decreased its activity except with strain TA102. The possible long-term hazards of C-nitroso compounds derived from drugs and dietary constituents are discussed in view of their pluripotent direct genotoxicity. 相似文献
11.
Methyl isocyanate (MIC) was tested for mutagenicity using the Ames Salmonella/microsome liquid-preincubation procedure with slight modification of test conditions. In the modification the preincubation mixture was incubated at 10 degrees C for 60 min. MIC was assayed both in the presence and absence of Aroclor-1254-induced S9, using 5 tester strains of Salmonella typhimurium, TA97a, TA98, TA100, TA102 and TA104. MIC induced mutagenic response in two base-pair substitution strains, TA100 and TA104, in the presence and absence of S9. However, mutagenic response in the presence of S9 was low as compared to that in the absence of S9. In the comparative mutagenic activity at 3 different preincubation test conditions (37 degrees C for 20 min, 20 degrees C for 40 min and 10 degrees C for 60 min), optimum mutagenic response was observed at 10 degrees C for the 60-min test condition. However, no mutagenic response was observed at 37 degrees C for the 20-min test condition. 相似文献
12.
Using the Ames plate reversion and fluctuation tests, the mutagenic activity of chloroquine was tested in the new tester strains of Salmonella typhimurium, TA97, TA102, and Escherichia coli strains WP2, WP2hcr, WP6 and WP67. The E. coli transconjugants obtained from the mating transfer of R-plasmid(s) in strains TA97 and TA102 respectively to E. coli WP2, i.e. EE97 and EE102, were also tested. Chloroquine reverted strain TA97 from histidine dependence to independence and also reverted E. coli strains EE97 and EE102 from tryptophan dependence to independence. The E. coli strains WP2, WP2hcr; WP6 and WP67 and S. typhimurium TA102 were not affected. S. typhimurium TA97 could be reverted with 250 ng/ml of chloroquine (therapeutic blood level of chloroquine is 300 ng/ml). Reversion generally occurred optimally at the relatively lower concentrations of chloroquine i.e. 25, 50 micrograms/ml than at higher concentrations. From the properties of the reverted tester strains, the results indicated that chloroquine per se mediated frameshift reversion. 相似文献
13.
Comparative extraction efficiency of the pre-packed Bakerbond-spe-SDB-1 resin and of Amberlite-AD2 (XAD-2) resin, for the preparation of urine extracts in biomonitoring studies. Urine extracts were prepared in parallel with the Bakerbond column and with the classical XAD-2 resin from urines (1) spiked with mutagenic chemicals, (2) collected from patients after chemotherapy, and (3) from smokers. Mutagenic activities were evaluated on Salmonella typhimurium tester strains TA97a, TA98, TA100 and TA102 with and without S9 mix. Mutagenic activities obtained with Bakerbond extracts were almost always higher or at least equivalent to those prepared on XAD-2 resin. Similar results were observed for the three urine sample groups. When fully validated, the use of the pre-packed columns will be more convenient and time-saving for large population studies. 相似文献
14.
Recently, mutagenic activity on several strains of Salmonella typhimurium has been found in many heat-processed foodstuffs. The previously reported direct-acting mutagenic activity of coffee in Salmonella typhimurium TA100 (Ames assay) was confirmed in our study. In addition to TA100, a mutagenic effect of coffee was also found by using the newly developed strain TA102. The mutagenic activity was abolished by the addition of rat-liver homogenate. 10% S9 mix completely eliminated the mutagenic activity of 30 mg of coffee per plate. The addition of reduced glutathione to active S9 further decreased the mutagenic activity and also reduced the mutagenicity together with inactivated S9. The compound or compounds responsible for this inactivation are heat-labile and seem to be located in the cytosol fraction of the S9. Part of the mutagenicity of coffee was also lost spontaneously upon incubation at temperatures between 0 degrees and 50 degrees C. The loss of activity was dependent on temperature, being more pronounced at 50 degrees C compared to 0 degrees C (at 50 degrees C approximately 50% of the mutagenic activity was lost after 6 h). As anaerobic conditions prevented this loss of mutagenicity almost totally, oxidative processes are probably responsible for the inactivation. The stability of the mutagen was not influenced by incubation at low pH values (pH 1-3), with or without the addition of pepsinogen. The mutagenic properties of methylglyoxal, which to some extent could be responsible for the mutagenic activity of coffee, were compared with those of coffee. Methylglyoxal was strongly mutagenic towards Salmonella typhimurium TA100 and TA102. Its mutagenic activity was partially inactivated by the addition of 10% S9. Glyoxalase I and II together with reduced glutathione abolished the mutagenic activity of methylglyoxal but reduced the mutagenicity of coffee by only 80%. Since these enzymes occur in mammalian cells, the mutagenic compound(s) of coffee could also be degraded in vivo. This conclusion is supported by the fact that a long-term carcinogenicity study with rats was negative. These results clearly demonstrate that the effects observed in vitro do not necessarily also occur in vivo, but that in vitro experiments may contribute to the understanding of fundamental mechanisms of chemical carcinogenesis. 相似文献
15.
Thirty compounds of various chemical classes were investigated for mutagenicity in a collaborative study (3 laboratories) using Salmonella typhimurium TA102. With 5 compounds, namely hydrazine sulfate, phenylhydrazine, hydralazine, glutardialdehyde and glyoxal, mutagenicity was detected by all laboratories. Formaldehyde was assessed as weakly mutagenic in only 1 of 3 laboratories. The remaining 24 agents were uniformly described as non-genotoxic in TA102. In spite of the overall good qualitative agreement in the mutagenicity results between the 3 laboratories some quantitative discrepancies occurred in the dose response of the mutagenic compounds. Varying inter- and intra-laboratory differences in the spontaneous rate of revertants were obtained. The usefulness of the tester strain TA102 in routine mutagenicity testing is discussed. 相似文献
16.
Benzo[b]phenanthro[2,3-d]thiophene (BPT), and a number of its metabolites, including BPT-3,4-diol, BPT sulfoxide, BPT sulfone, and 3-hydroxyBPT were assessed for their mutagenic activity in Salmonella typhimurium strain TA100, and S. typhimurium base-specific strains TA7001, TA7002, TA7003, TA7004, TA7005, and TA7006. Among the compounds tested in strain TA100, BPT, BPT sulfone, and 3-hydroxyBPT did not show any significant mutagenic response in the presence of S9. In contrast BPT sulfoxide and BPT-3,4-diol (a precursor to the bay-region diol epoxide of BPT) showed significant mutagenic activity in the presence of S9. Surprisingly, BPT sulfoxide was nearly 3.3-fold more mutagenic than BPT-3,4-diol in the presence of S9. BPT sulfoxide also displayed intrinsic mutagenic activity, which was nearly 1.5-fold less than that displayed by BPT-3,4-diol in the presence of S9. In base specific tester strains, BPT sulfoxide was the most active metabolite in strains TA7002, TA7004, and TA7005 with S9 activation. In these strains, BPT-3,4-diol was 2- to 7-fold less mutagenic than BPT sulfoxide in the presence of S9. Only in strain TA7006, BPT-3,4-diol was four-fold more mutagenic than BPT sulfoxide. The fact that BPT sulfoxide is significantly more mutagenic than BPT-3,4-diol in S. typhimurium strain TA100 suggests that the formation of sulfoxide may be the principal pathway for the metabolic activation of BPT to mutagenic products. Based on the results from Tester Strain TA7005, it indicate that BPT and its most mutagenic metabolite BPT sulfoxide induce predominantly CG --> AT transversion, which is observed as the most frequent base substitution mutation of p53 tumor-suppressor gene in human lung cancer. 相似文献
17.
Photomutagenicity of 16 polycyclic aromatic hydrocarbons from the US EPA priority pollutant list 总被引:13,自引:0,他引:13
The photomutagenicity of 16 polycyclic aromatic hydrocarbons (PAHs), all on the United States Environmental Protection Agency (US EPA) priority pollutant list, was studied. Concomitant exposing the Salmonella typhimurium bacteria strain TA102 to one of the PAHs and light (1.1 J/cm2 UVA+2.1 J/cm2 visible) without the activation enzyme S9, strong photomutagenic response is observed for anthracene, benz[a]anthracene, benzo[ghi]perylene, benzo[a]pyrene, indeno[1,2,3-cd]pyrene, and pyrene. Under the same conditions, acenaphthene, acenaphthylene, benzo[k]fluoranthene, chrysene, and fluorene are weakly photomutagenic. Benzo[b]fluoranthene, fluoranthene, naphthalene, phenanthrene, and dibenz[a,h]anthracene are not photomutagenic. These results indicate that PAHs can be activated by light and become mutagenic in Salmonella TA102 bacteria. At the same time, the mutagenicity for all the 16 PAHs was examined with the standard mutagenicity test with 10% S9 as the activation system. Benzo[b]fluoranthene, benzo[k]fluoranthene, chrysene, acenaphthylene, and fluorene are weakly mutagenic, while the rest of the PAHs are not. In general, the photomutagenicity of PAHs in TA102 does not correlate with their S9-activated mutagenicity in either TA102 or TA98/TA100 since they involve different activation mechanisms. 相似文献
18.
Mutagenicity and DNA-damaging activity for several pesticides tested with Bacillus subtilis mutants 总被引:1,自引:0,他引:1
The active pure compounds of 4 pesticides were tested for DNA-damaging and mutagenic activity in Bacillus subtilis and Salmonella typhimurium tester strains. Included were zinc ethylenebisdithiocarbamate (dithane), 1,2-dihydropyridazine-3,6-dione (maleic hydrazide), O,O-dimethylphosphorodithioate (malathion), and 1,2-dibromoethane (fumazone). These agents gave either weak or negative mutagenic responses with the Salmonella/microsome tests for mutagenicity, but were all positive when the tester was B. subtilis strain TKJ6321. Of the 4 chemicals, only fumazone required metabolic activation with rat-liver S9 mix. Upon activation, it produced a volatile mutagenic product. Dithane, maleic hydrazide, and malathion were all mutagenic and did not require metabolic activation. Among these agents, dithane was strongly mutagenic while fumazone, maleic hydrazide and malathion were moderately mutagenic. Only dithane gave significant DNA-damaging activity when applied to a battery of repair-deficient B. subtilis mutants. For the chemicals reported, it is concluded that B. subtilis is superior to S. typhimurium in the detection of mutagenic activity. We strongly recommend its use for prescreening procedures in combination with the S. typhimurium testers. 相似文献
19.
The role of reactions of conjugation with uridine diphosphoglucuronic acid (UDPGA) and with 3-phosphoadenosine-5-phosphosulfate (PAPS) in modification of the mutagenic effect of diethyl nitrosamine (DENA), nitrosomorpholine (NM) and cyclophosphane (CP) was studied by the Ames test. It was shown that adding UDPGA to the activating mixture significantly decreased the level of the mutagenic effect of DENA, NM and CP on bacteria Salmonella typhimurium TA 1950, when S9 and microsomal fractions of rat liver homogenate were used. Adding PAPS to the activating mixture when S9 and cytosole fractions were used, did not affect mutagenic action of DENA on S. typhimurium TA 1950 and TA 1535, enhancing the mutagenic effect of CP on TA 1535, with no such influence on TA 1950. Introduction of PAPS into the activating mixture elevated the mutagenic effect of NM on both bacterial strains using S9 fraction but not cytosole fraction. 相似文献
20.
Aristolochic acid (1), a constituent of Aristolochia species, has been used for medicinal purposes since the Graeco-Roman period. Following the observation that the compound was mutagenic and carcinogenic, it was removed from pharmaceutical products. Consistent with previous reports, we have found that 1 serves as a direct-acting mutagen in Salmonella typhimurium strains TA100, TA102, TA1537 and TM677, but was not active in the nitroreductase-deficient strains TA98NR and TA100NR. However, aristolic acid (2), a compound that differs in structure only by the absence of the nitro group, was also found to be a direct-acting mutagen in Salmonella strains TA98, TA100, TA102, TA1537, and TM677, as well as strains TA98NR and TA100NR. Both compounds (1 and 2) were active mutagens when evaluated with cultured Chinese hamster ovary cells. Thus, in contrast to previous suggestions, the nitro group at position 10 is not required to induce a mutagenic response. Also, a series of structural relatives (the methyl esters of 1 and 2 (3 and 4, respectively), aristolochic acid-D (5), aristolactam (6), aristolactam A-II (7), and aristolactam-N-beta-D-glucoside (8)) were evaluated for mutagenic potential with Salmonella typhimurium strain TM677 and found to be inactive. Since compounds 3 and 4 were found to be active mutagens with Salmonella typhimurium strains TA98, TA100, TA102 and TA1537 (sufficient quantities of compounds 5-8 were not available for testing), differential sensitivity of the tester strains unrelated to mutagenic potential is suggested. Further, compounds 1, 2, and 6-8 were evaluated for potential to inhibit growth with cultured KB or P388 cells. P388 cells were substantially more sensitive, and compound 1 was the most active of the materials tested (ED5 = 0.58 microM). Compound 6 also demonstrated appreciable activity (ED50 = 4.2 microM), as did compound 8 (ED50 = 6.0 microM). It therefore appears that phenanthrene-ring substituents, in addition to the nitro group at position 10, serve important roles for biological potential. In considering the carcinogenic event induced by aristolochic acid, these functionalities should also be taken into account. 相似文献