摘要:

AbstractHuman diploid fibroblasts (strain VH‐10) were exposed to the direct‐acting alkylating agent, ethylene oxide (EtO), in vitro, and the frequency of HPRT mutants was evaluated by selection in medium containing 6‐thioguanine. A dose‐dependent increase of the mutant frequency was found in the dose range of 2.5–10 mMh of EtO. The EtO‐induced mutant frequency increased 5–19 times the background frequency at low or moderately toxic doses, which indicates that EtO is a strong mutagen in human fibroblasts in vitro. The mutagenic potency was 9.8

ISSN:0893-6692    

DOI:10.1002/em.2850190203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractTwenty‐eight chlorinated organic compounds were evaluated for their ability to induce DNA damage using the Microscreen prophage‐induction assay inEscherichia coli.Comparison of the performance characteristics of the prophage‐induction andSalmonellaassays to rodent carcinogenicity assays showed that the prophage‐induction assay had a somewhat higher specificity than did theSalmonellaassay (70% vs. 50%); sensitivity, concordance, and positive and negative predictivity were similar for the two microbial assays. The Microscreen prophage‐induction assay failed to detect eight carcinogens, perhaps due to toxicity or other unknown factors; five of these eight carcinogens were detected by theSalmonellaassay. However, the prophage‐induction assay did detect six carcinogens that were not detected by theSalmonellaassay, and five of these were single‐species, single‐site carcinogens, mostly mouse liver carcinogens. Some of these carcinogens, such as the chloroethanes, produce free radicals, which may be the basis for their carcinogenicity and ability to induce prophage. The prophage‐induction (or other SOS) assay may be useful in identifying some genotoxic chlorinated carcinogens that induce DNA damage that does not revert the standardSalmone

ISSN:0893-6692    

DOI:10.1002/em.2850190204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThree species of marine bivalve molluscs (Chamelea gallina, Ruditapes decussatus, andCrassostrea gigas) have been studied in order to evaluate the levels of pollution on the South Atlantic Spanish littoral. Several transition metals (Cu, As, Cd, Sn, Hg, Pb) were determined as a general index of total contamination. Animals from putative contaminated areas exhibited higher metal contents than those from cleaner waters.C. gigasshowed 5–20‐fold higher total metal content than the other two species. The mutagenicity of ethanolic extracts was assayed by using both the His reversion and the Ara forward mutation tests. Mollusc tissues from the three species did not contain genotoxins active on TA98 (frameshift mutations) or TA100 (mainly G:C base‐pair substitutions), but did contain direct‐acting genotoxins of a polar nature and oxidative type. This was based on the following observations: 1) mammalian metabolic activation was not required for mutagenicity, 2) mutagens were eluted with the polar fraction from XAD‐2 columns, and 3) mutagenic responses were observed withSalmonella typhimuriumTA102 (A:T base‐pair substitutions; sensitive to oxidative damages) andEscherichia colicatalase‐deficient (AraRforward mutations) strains. No relevant differences were found in the mutagenicity of mollusc extracts from areas with different pollution levels. Otherwise, our data suggest that, in general, animals living in contaminated environments had fewer genotoxins of oxidative type than those from less polluted areas. Such a result might be explained by the observation of increased levels of a number of detoxifying and antioxidant enzymes, such as glutathione‐S‐transferase, glutathione‐peroxidase, catalase, and superoxide dismutase. Thus, contaminated animals seem to be better protected against the oxidative damages induced by metals, in agreement with their lower malondialdehyde levels. To what extent the responsible mutagenic compounds are of endogenous origins, or “Nature's pesticides” (the major toxic chemicals ingested by phytoplankton filterfeeders), and/or the result of human activities r

ISSN:0893-6692    

DOI:10.1002/em.2850190205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractA micronucleus assay based on cytogenetic analysis of early spermatids (Tates et al.;Mutation Research121:131–138, 1983) was applied to determine if the chelating agent ethylenedinitrilotetraacetic acid (EDTA) may induce aneuploidy in mouse meiotic cells. Previous results indicated aneuploidogenic activity of EDTA inDrosophilafemale germ cells (induction of chromosome loss; Zordan et al.:Environ Mol Mutagen15:205–213, 1990). In the same study, a standard aneuploidy test based on chromosome counting in mouse secondary spermatocytes failed however to show aneuploidogenic properties of FDTA in mouse somatic and germ cells. In the present study the effects of two clastogens, adriamycin (ADM) and mitomycin C (MMC), and of the aneuploidogenic agent chloral hydrate (CH) were also evaluated. All compounds were tested at a single dose level and at two time intervals corresponding to the treatment of diakinesis/metaphase I/metaphase II spermatocytes. The clastogenic potential of the compounds under study was also evaluated, by chromosomal aberration analysis in mouse spermatogonia, in an independent set of experiments. The results obtained indicate that ADM, CH and EDTA are able to induce micronuclei at meiosis. On the contrary, only ADM and MMC induced chromosomal aberrations in mouse spermatogonia. Therefore, the most probable origin of micronuclei produced by CH and EDTA is whole chromosome lagging. These results provide further evidence for the aneuploidogenic properties of these chelating age

ISSN:0893-6692    

DOI:10.1002/em.2850190206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractCoumarin has been shown to be an effective inhibitor of carcinogenesis in rodents if given before and during the carcinogen treatment. We investigated the possibility that pretreatment with coumarin would inhibit the genotoxicity of benzo(a)pyrene (BP) in ICR mice as indicated by the bone marrow micronucleus test, a widely used in vivo test for genotoxicity. Our studies showed that pretreatment of male mice with doses of coumarin at 65 or 130 mg/kg/day for 1 week (with 1 day of no treatment at midweek) partially inhibited the genotoxicity of BP at a single intraperitoneal dose of 150 mg/kg. Time course experiments showed a decrease in induced micronuclei in the bone marrow at several time points after the BP treatment, thus indicating a true inhibition and not a lag in the induction of micronuclei. However, no inhibition in micronuclei formation was seen in female mice pretreated with the same doses of coumarin. Coumarin treatment alone did not induce micronuclei in either sex. Future studies are needed to analyze the mechanisms responsible for the difference noted between the sexes.

ISSN:0893-6692    

DOI:10.1002/em.2850190207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe mutagenesis of metals in bacteria, as reported in the literature, can best be described as inconsistent. We report that cobalt chloride (Co++), ferrous sulfate (Fe++), manganese sulfate (Mn++), cadmium chloride (Cd++), and zinc chloride (Zn++) could be reproducibly detected as mutagens inSalmonellastrain TA97 when preincubation exposures were made in sterile, distilled, deionized water, or in Hepes buffer in NaCl2/KCl2, rather than the standard sodium phosphate buffer. Co++was also mutagenic under standard preincubation conditions. The individual components of Vogel‐Bonner medium, i.e., potassium and ammonium phosphates, citrate, and magnesium sulfate, inhibit mutagenesis by these metals. The phosphates and the citrate probably inhibit by chelating the metals, while data are presented to suggest that Mg++inhibition of metal mutagenesis is due to competitive inhibition for active transport via the magnesium active transport system inSalmonella.The chelator, diethyldithiocarbamate, inhibited the mutagenicity of Co++, Fe++, Zn++, and Mn++, but enhanced the mutagenicity of Cd++. The results presented show that divalent metals can be detected as mutagens inSalmonella, and that their lack of detection as mutagens is not due to an inherent insensitivity of Salmonella but to their interaction with media components and/or passive and active transport processe

ISSN:0893-6692    

DOI:10.1002/em.2850190208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

Abstract1‐Nitrosopyrene, a metabolite of the tumorigenic environmental pollutant 1‐nitropyrene, is a potent mutagen at thehprtlocus in Chinese hamster ovary (CHO) cells. A single DNA adduct,N‐(deoxyguanosin‐8‐yl)‐1‐aminopyrene, is produced in CHO cells treated with 1‐nitrosopyrene, and this adduct is found in rats and mice exposed to 1‐nitropyrene. In this study, the structure of thehprtgene and the structure and amount ofhprtmRNA were analyzed in 43 CHO cell mutants (16 isolated from solvent control cultures and 27 isolated from 1‐nitrosopyrene‐treated cultures).Pstl‐ andBamHl‐digested DNA from the mutants were subjected to Southern blot analysis using a hamsterhprtcDNA probe. None of the 1‐nitrosopyrene‐induced mutants and only one of the control mutants displayed hybridization patterns that were different from the parent CHO cells. Northern blot analysis revealed that two control mutants had truncatedhprtmRNAs, while 56% of the control mutants and 78% of the induced mutants had reduced levels ofhprtmRNA. Using polymerase chain reaction amplification of cDNA synthesized from RNA, thehprtprotein‐coding region could be amplified from 23 of the 1‐nitrosopyrene‐induced mutants and 11 of the control mutants. The amplification products from 3 of the control mutants and 5 of the induced mutants were smaller than that found with RNA from parental CHO cells. These results indicate that the mutagenic DNA damage produced by 1‐nitrosopyrene in CHO cells does not cause major structural alterations in thehprtgene and suggest that 1‐nitrosopyrene acts as a point mutagen. A large number of both control and 1‐nitrosopyrene‐induced mutants exhibited a marked reduction inhprtmRNA concentration or possessed truncated mRNAhprtprotein coding sequences. These alterations may contribu

ISSN:0893-6692    

DOI:10.1002/em.2850190209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractNitrobenzo[a]pyrenes (NBaPs) are ubiquitous environmental pollutants that produce mulations inSalmonella typhimuriumand Chinese hamster ovary cells. In this study, 1‐, 3‐, and 6‐NBaP induced amplification of SV40 DNA sequences in an SV40‐transformed Chinese hamster embryo cell line which is sensitive to DNA amplification by various known carcinogens. Of the three isomers, 3‐NBaP produced the highest level of gene amplification, which was 4.8 relative to untreated controls at a dose of 5 μg/ml. Considering the relationship between gene amplification and tumorigenesis, it seems prudent to carry out a more exhaustive analysis of the carcinogenic potential of th

ISSN:0893-6692    

DOI:10.1002/em.2850190210

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe liver carcinogen phenobarbital (PB) causes a weak but reproducible increase of the mutant frequency in the Ames test, strain TA1535, without S9. Since there is no obvious chemical basis for a “DNA reactivity” of this compound experiments were performed to obtain information about possible indirect mechanisms of enhancing the number of spontaneous mutant colonies. In the course of the study strong synergistic and comutagenic effects of PB when given in combination with Na‐azide or 2‐aminoanthracene (2AA) were observed. Not only TA1535 but the complete set of tester strains was responsive. However, PB did not enhance the effects of other mutagens such as 4‐nitroquinoline N‐oxide or 2‐nitrofluorene. It is argued that in strain TA1535 the fixation and expression of spontaneously occurring DNA lesions is amenable to modulation by PB similar to that of Na‐azide or 2AA induced lesions. Thus in the usual sense, PB is not genotoxic in the Ames test. Methapyrilene, another liver carcinogen with an assumed non‐genotoxic mode of action, showed almost identical properties in

ISSN:0893-6692    

DOI:10.1002/em.2850190211

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe mutagenic and genotoxic activities of 48 nitroimidazoles and related imidazole derivatives have been evaluated by using modified versions of the Ames test and the SOS Chromotest.Salmonella typhimuriumtester strain TA 100 was used with and without metabolic activation in the Ames test and Escherichia coli tester Strain PQ 37 was used with and without metabolic activation in the SOS Chromotest. Including metronidazole and dimetridazole, 45 derivatives were mutagenic and genotoxic. The mutagenic potencies (MP) ranged from 0.127 to 53,717 revertants/nmol while the SOS induction powers (SOSIP) ranged from 0.00131 to 107 IF/nmol. The overall correlation between MP and SOSIP was r = 0.845 (n = 84) as calculated by linear regression analysis. A higher correlation was observed between MP and SOSIP without the S9 mix than with it. Among the imidazole derivatives, the 5‐nitroimidazoles with a lactam ring at the 2‐position showed the highest MP and SOSIP. The presence of a nitro group at the 5‐position was critical for the mutagenicity and the genotoxicity of the derivatives. Substituents at the 1‐ and 2‐positions were also found to modulate these a

ISSN:0893-6692    

DOI:10.1002/em.2850190212

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY