摘要:

AbstractTrichloroethylene (TCE) is a high production volume chemical frequently stabilized with oxiranes. These oxiranes may be responsible for the mutagenic activity of TCE inSalmonella, which has been occasionally, but not consistently, reported. High purity and oxirane‐stabilized TCE samples were tested for their mutagenic potential inSalmonella typhimuriumstrains TA 1535, TA 98, and TA 100. Stabilized TCE was tested using a preincubation protocol up to a dose level of 10,000 μ per plate, but no mutagenic response was observed in either the presence or absence of a supplementary metabolic activation system (S9 mix) derived from Aroclor 1254‐induced male rat liver. TCE without oxirane stabilizers also was nonmutagenic when tested in a vapor delivery system at nominal concentrations of up to 20% and using S9 mix derived from either rat or hamster. TCE containing 0.5–0.6% 1, 2‐epoxybutane did induce mutagenic responses from strains TA 1535 and TA 100 in the presence and absence of S9 mix. The lowest effective dose was about 0.63% in TA 1535 in the absence of S9 mix. Vapor‐phase tests with 1, 2‐epoxybutane showed that an atmospheric concentration of 0.009% could induce 12‐fold and 3‐fold increases, respectively, in strains TA 1535 and TA 100. These increases would account for the mutagenic activity of the stabilized TCE sample. Epichlorohydrin (another commonly used stabilizer) induced similar increases in mutant numbers at an atmospheric concentration of 0.0009%. The absence of a significant response caused by unstabilized TCE in the presence of S9 mix is probably due to a lack of assay sensitivity, since chloral, a metabolite of TCE, is a mutagen in TA 100 [Haworth et al.:Environ Mutagen[Supplement 1

ISSN:0893-6692    

DOI:10.1002/em.2850130302

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

年代:1989

数据来源: WILEY

摘要:

AbstractPrevious studies showed that binary mixtures of the environmental pollutants 1‐ and 3‐nitrobenzo[a]pyrene produced a synergistic mutational response in theSalmonellareversion assay. Since nitroreduction is believed to mediate the direct‐acting mutagenicity of the individual compounds, we have examined the role of nitroreduction in the mutagenicity of mixtures of 1 ‐ and 3‐nitrobenzo[a]pyrene in theSalmonellaplate incorporation assay. While mixtures of 1 ‐ and 3‐nitrobenzo[a]pyrene induced up to 183% more revertants in strain TA98 than produced by equivalent amounts of the individual compounds, in the nitroreductase‐deficient strain TA98NR the same mixtures only induced up to 57% more revertants than the individual compounds. Analysis of mixtures of 1 ‐ and 3‐nitrosobenzo[a]pyrene (the two‐electron reduction products of 1 ‐ and 3‐nitrobenzo[a]pyrene) for mutation induction in TA98 yielded no evidence of a synergistic effect between the compounds. The mutagenicity of the mixtures was dependent upon the amount of the more mutagenic component.Salmonellacultures were also incubated with mixtures of 1 ‐ and 3‐nitrobenzo[a]pyrene, as well as with equivalent amounts of the individual compounds. In two experiments, nitroreductive ability, as measured by the amount of 1 ‐nitropyrene metabolized to 1 ‐aminopyrene in 1 hr, was increased 9 to 105% in cultures pretreated with the mixtures as compared with cultures pretreated with the individual compounds. The results of this study support the hypothesis that nitroreduction is a major factor in the synergistic mutational response induced by 1 ‐ and 3‐nitrobe

ISSN:0893-6692    

DOI:10.1002/em.2850130303

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

年代:1989

数据来源: WILEY

摘要:

AbstractAlkaline elution is a sensitive and commonly used technique to detect cellular DNA damage in the form of DNA strand breaks and DNA cross‐links. Conventional alkaline elution procedures have extensive equipment requirements and are tedious to perform. Our laboratory recently presented a rapid, simplified, and sensitive modification of the alkaline elution technique to detect carcinogen‐induced DNA strand breaks. In the present study, we have further modified this technique to enable the rapid characterization of chemically induced DNA‐interstrand and DNA‐protein associated cross‐links in cultured epithelial cells. Cells were exposed to three known DNA cross‐linking agents, nitrogen mustard (HN2), mitomycin C (MMC), or ultraviolet irradiation (UV). One hour exposures of HN2 at 0.25, 1.0, and 4.0 μM or of MMC at 20, 40, and 60 μM produced a dose‐dependent induction of total DNA cross‐links by these agents. Digestion with proteinase K revealed that HN2 and MMC induced both DNA‐protein cross‐links and DNA‐interstrand cross‐links. Ultraviolet irradiation induced both DNA cross‐links and DNA strand breaks, the latter of which were either protein and nonprotein associated. The results demonstrate that gravity‐flow alkaline elution is a sensitive and accurate method to characterize the molecular events of DNA cross‐linking. Using this procedure, elution of DNA from treated cells is completed in 1 hr, and only three fractions per sample are analyzed. This method may be useful as a rapid screening assay for genotoxicity and/or as an adjunct to other predictive assays for potential m

ISSN:0893-6692    

DOI:10.1002/em.2850130304

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe industrial chemical acrylamide is suspected to induce potentially heritable genetic damage. While several studies in rodents have indicated that this substance can damage spermiogenic cells, resulting in dominant lethals and heritable translocations, cytogenetic assessments of premeiotic and meiotic cells after exposure have produced equivocal results. In the present study, various cytogenetic endpoints in both somatic and germ‐line cells from acrylamide‐treated mice were evaluated. Sister chromatid exchanges and micronuclei, but not chromosome aberrations, were induced in spleen cells; synaptonemal complex irregularities (asynapsis), but not chromosome aberrations, were induced in germ ce

ISSN:0893-6692    

DOI:10.1002/em.2850130305

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe mutagenic activity of airborne particulate matter collected in Pisa, a small nonindustrial town located in Italy, has been monitored over 1 year using the AmesSalmonellaTest. Airborne particulate was collected on fibreglass filters using a Hi‐Vol sampler and extracted by sonication and Soxhlet acetone extraction in sequence. TA 98 and TA 100 salmonella strains gave positive results with the great majority of samples. The mutagenicity trend fits with a harmonic regression with a peak during December/January and inversely correlates with the temperature. No correlations were observed with other meteorological conditions such as wind, cloud, rainfall, atmospheric pressure, and humidity. The ratio between mutagenicity/μg of particulate matter with S9 and that without S9 remains more or less constant regardless of seasonal fluctuations, suggesting that during cold months quantitative increases of mutagens onto particulate matter have probably occurred. The comparison of air mutagenicity in different sites suggests that motor vehicle exhaust fumes are the major source of air pollution. Finally, because of high‐traffic volume, air mutagenicity at street level is comparable to that observed in several metropolitan areas all over the w

ISSN:0893-6692    

DOI:10.1002/em.2850130306

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

年代:1989

数据来源: WILEY

摘要:

AbstractTertiary butyl hydroquinone (TBHQ)—a phenolic antioxidant, was evaluated by assessing the induction of sister chromatid exchanges (SCEs) in bone marrow metaphase cells of mice. Six concentrations, 0.5, 2, 20, 50, 100, and 200 mg/kg, of TBHQ were injected intraperitoneally. A positive dose‐response effect in the SCE frequency was observed using the Cochran‐Armitage trend test. Two mg/kg of TBHQ was found to be the minimum effective dose. Study of the cell‐cycle kinetics showed a delay in cell cycle induced by the higher concentrations of TBHQ. Thus, TBHQ was found to be a DNA damage‐inducing agent and also a cytotoxic chemical in viv

ISSN:0893-6692    

DOI:10.1002/em.2850130307

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

年代:1989

数据来源: WILEY

摘要:

AbstractIn recent years, evidence has accumulated that suggests that mammalian topoisomerase may play a role in the formation of spontaneous or chemically induced sister chromatid exchange (SCE). In microbial systems, nalidixic acid is known to disrupt the function of a topoisom‐erase‐like enzyme, DNA gyrase. To explore the possible relationship to topoisomerase function and SCE formation in mammalian cells, an analog of nalidixic acid with potent topoisomerase II inhibitory activity was selected for examination in a variety of genetic toxicology assays. This analog, CP‐67, 015, proved to be a positive direct‐acting mutagen in the L5178Y/TK+/‐, CHO/ HGPRT, and V79/HGPRT systems. However, no gene mutational activity was observed using the Ames test in direct plate, mouse and rat metabolic activation, and mouse urine tests. In vitro cytogenetic studies showed strong clastogenic activity in human lymphocytes and in CHO cells. Compound‐induced chromosome damage was also observed in vivo in mouse bone marrow cells. Surprisingly, SCE studies in vitro in human lymphocytes or CHO cells showed only slight increases, even at levels producing severe chromosome breakage. Mouse bone marrow showed no significant elevation of SCE following parenteral treatment with CP‐67, 015.These results, taken together, demonstrate that CP‐67, 015 is a direct‐acting mutagen in mammalian cells with both gene and chromosomal level effects. The relative ineffectiveness in producing SCEs suggests that CP‐67, 015 may interfere with a DNA replicative/repair process, perhaps by alteration of one or more DNA polymerase activities. This suggestion is based in part on the known effect of the analog nalidixic acid on DNA gyrase in microbial cells and on topoisomerase in mammalian cells. The profile of genetic activity of CP‐67, 015, coupled with its inhibitory effect on topoisomerase function, gives rise to a model for SCE formation that is based on anomalies of topoisomerase activity

ISSN:0893-6692    

DOI:10.1002/em.2850130308

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

年代:1989

数据来源: WILEY

摘要:

AbstractAdherent peritoneal exudate cells rich in macro‐phages were harvested from Cornell K‐strain chickens 42 hr after i.p. stimulation with Sephadex G‐50. Glass‐adherent monolayers were obtained on coverslips and subjected to in vitro exposure to methyl methanesulfonate (MMS) at various doses for 1 hr. Solvent (0.17% ethanol final concentration) and sham (RPMI 1640 growth media) exposures were also performed. At selected times after exposure, the macrophages were analyzed for cell viability, adherence, DMA damage, and functional activity. Although MMS doses of 5 × 10−3M and 1 × 10−3M concentrations resulted in significant cytoxicity, 2 × 10−4M had no significant cytotoxic effect. However, this exposure resulted in DNA damage as measured by alkaline elution. Concomitant with the DNA damage was a significant decrease in the phagocytic activity of macrophages. Repair of MMS‐induced DMA lesions in macrophages was indicated by a normal DNA alkaline elution profile 10 hr postrecovery. Functional activity of cells also returned to normal levels. In contrast, the incidence of Fc receptor‐positive cells detected by rosetting increased immediately after MMS exposure, and phagocytosis of opsonized SRBCs was not affected by 2 × 10−4M MMS treatment. Similarly, MMS treatment did not alter the acid phosphatase activity of macrophages. However, bactericidal ability of MMS‐treated macrophages for unopsonizedEscherichia coliwas significantly depressed. These results suggest that the avion macrophage is a useful target cell for examining possible relationships between genotoxic and immunotoxic effects

ISSN:0893-6692    

DOI:10.1002/em.2850130309

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

年代:1989

数据来源: WILEY

摘要:

AbstractSodium azide mutagenesis is mediated through a metabolic intermediate in bacteria and plant species. However, very little is known about the interaction of this intermediate with nucleic acids, its genotoxic potential, or its mechanism of action, especially in mammalian cells. Chinese hamster cells and normal human skin fibroblasts were treated with extracts fromSalmonella typhimuriumorHordeum vulgare(barley) containing a crude mutagenic metabolite, as well as with synthetically produced azidoalanine. The cells were evaluated for the induction of sister chromatid exchanges and the ability to perform unscheduled DNA synthesis. With the purified azidoalanine and the azide‐treated extracts fromHordeum vulgare, there was a statistically significant increase in the frequency of sister chromatid exchanges observed in both Chinese hamster cells and human fibroblasts. This increase was about twofold, as compared with the control. On the other hand, there was no detectable genotoxic response when cells were exposed to azide‐treated extract fromSalmonella typhimurium.The results imply that azidoalanine and the crude mutagenic metabolite fromHordeum vulgareare weakly genotoxic in mammalian ce

ISSN:0893-6692    

DOI:10.1002/em.2850130310

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe azo dyes Sunset Yellow and Orange II were gavaged to rodent species to check bile, urine, and fecal extracts for possible mutagenic activity in the Ames test or in bone marrow cells for clastogenicity using cytogenetic test systems. After oral application the dyes showed a negative response in bile, excrements, and bone marrow. When an exogenous metabolic activation was performed, increased revertant numbers usingSalmonellastrain TA100 were obtained only in fecal extracts of Sunset Yellow‐treated animals. It is concluded that no genotoxic harm is to be expected from the ingestion of Sunset Yellow or Orange I

ISSN:0893-6692    

DOI:10.1002/em.2850130311

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

年代:1989

数据来源: WILEY