Mutation Research\/environmental Mutagenesis and Related Subjects最新文献

In a preliminary study Bamezai and Kumar (1992) reported that a 24-h period of sleep deprivation may raise sister chromatid exchange (SCE) frequencies up to 193% in peripheral blood lymphocytes. This was reinvestigated to clarify the role of sleep duration as a confounder for SCE, which is a well-established parameter dor biomonitoring in occupational medicine. In our study, the SCE baseline and the influence of a 24-h period of sleep deprivation (test period) on SCE were investigated for 20 non-smoking volunteers (10 females and 10 males; 20–29 years of age). There was no significant difference (P_all = 0.094) between the deviations of the two SCE rates of the control period (mean: −0.21 ± 0.90 SCE) and the differences between SCE rates before and after sleep deprivation (mean: 0.4 ± 0.94 SCE) of each proband. No significant difference was detected between females and males, and SCE did not correlate with age or sleep duration. Therefore we conclude that the influence of sleep deficit on SCE is in the range of a normal day-to-day variance, and has not to be taken into account when SCE is used for a genotoxic monitoring at the workplaces.

Cigarette smokers have been reported to void urine which is more mutagenic, as measured in the Ames assay, than urine voided by non-smokers. Condensate from the mainstream smoke of a cigarette which primarily heats tobacco (test cigarette) has shown significantly reduced mutagenicity in a battery of in vitro genotoxicity assays compared with tobacco-burning cigarettes. The objective of this study was to determine whether the reduction in mutagenic activity observed in the in vitro assays would be reflected in the urine of smokers of the test cigarette. Twenty smokers were enroled in a 4-week crossover study, with each smoker consuming test cigarettes ad libitum for a week and their usual brand of tobacco-burning cigarettes the other 3 weeks. Diet was strictly controlled throughout the study, and broiled and pan-fried meat was not served to minimize ingestion of mutagenic protein pyrolysis products. There was no statistically significant difference (p = 0.06) in consumption of tobacco-heating and tobacco-burning cigarettes. There were no statistically significant differences (p = 0.22) in salivary cotinine concentrations for smokers when smoking either tobacco-burning or tobacco-heating cigarettes. Urinary nicotine (ng/mg creatinine) was not different (p = 0.31) for smokers when smoking either tobacco-burning or tobacco-heating cigarettes. Urinary cotinine (ng/mg creatinine) was 32% lower (p = 0.0004) when smoking tobacco-heating cigarettes as compared with smoking tobacco-burning cigarettes. Twenty-four-hour urine samples were collected twice weekly, concentrated using XAD-2 resin and tested in Ames strains TA98 and YG1024 with metabolic activation. Tobacco-burning cigarette smokers experienced a 79% reduction in urinary mutagenicity as measured in strain YG1024 and a 72% reduction as measured in strain TA98 during the week that they smoked the tobacco-heating cigarette while maintaining a fixed dietary regimen. The results of this study indicate that smokers of tobacco-heating cigarettes void urine which is significantly less mutagenic than urine voided by smokers of tobacco-burning cigarettes.

Mothers who resided in Brownsville, Texas and who had children with neural tube defects (NTD) were studied to determine whether exposure to environmental mutagens may be a cause of abnormal reproductive outcomes. Peripheral blood lymphocytes from 19 of the mothers who had children with NTD and from 14 matched mothers who had normal children and who resided in Corpus Christi, Texas were investigated using the standard cytogenetic assay and a challenge assay to determine the existence of chromosome aberrations and abnormal DNA repair response. No differences were observed when the spontaneous and the challenged chromosome aberration frequencies were compared between the core and the control groups. Our data suggests that the core group was not exposed to mutagens at levels to cause significant increases of chromosome aberrations or to cause abnormal DNA repair response as determined by our assays. However, exposure to non-mutagenic environmental teratogens cannot be ruled out.

The plant Solanum trilobatum is mainly used for asthma, chronic febrile affections and difficult parturition. The active principle (Sobatum) obtained from the petroleum ether extract of the plant was proved as an anticancer agent by in vitro and in vivo experiments. Here, an effort was made to evaluate the induction of micronucleus by the Sobatum in the bone marrow of swiss mice. The micronucleus assay was conducted after 24 and 72 h of second administration of the Sobatum. The first set of experiments (24 h after second administration) consisted of 4 groups with 3 male Swiss albino mice each. The first group (as control) received only dimethyl sulfoxide, the second, third and fourth groups received different doses of the Sobatum (100, 200, 400 mg/kg body weight), and the fifth group (as positive control) received cyclophosphamide (100 mg/kg body weight) by i.p. injection. In the second set of experiment (72 h after the second administration) consisting of 5 groups, the first, as control, received dimethyl sulfoxide, the second, third and fourth groups received different concentrations of the Sobatum (100, 200, 400 mg/kg body weight), and the fifth group as positive control received cyclophosphamide (100 mg/kg body weight). All the animals of the first and second sets of experiment were killed 24 and 72 h after the second medication (2 consecutive days), and bone marrow smears were prepared, stained with May-Grunwald and Giemsa stain, and evaluated for the evidence of micronucleus. The study concluded that the Sobatum fails to influence the induction of micronuclei in bone marrow erythrocytes of mice 24 and 72 h after the second administration, thereby proving that Sobatum to has no cytogenetic toxic potential.

The presence of structural chromosome aberrations and sister chromatid exchange frequencies (SCE) were studied in lymphocytes from 28 male subjects occupationally exposed to vinyl chloride monomer for a period of 9 years. A significant increase in chromosomal damages and elevated SCE frequencies was detected during the third and fourth year of the follow-up study. During the last 2 years, all examined parameters are approaching control values. This is a result of decreasing vinyl chloride monomer concentrations in the working environment without interrupting the working process.

A bacterial photomutagenicity test system has been established according to a predetermined protocol using a light source emitting multiple wave lengths, including UV-A and UV-B, and the tester strains used for standard bacterial mutagenicity testing. 8-Methoxypsoralen (8-MOP) was used as a photomutagenic positive control showing no mutagenicity in the absence of light and borderline (Salmonella typhimurium TA1537) or clear (Salmonella typhimurium TA102 and Escherichia coli WP2) mutagenic effects in the presence of light. Using the same experimental conditions, the UV filters p-aminobenzoic acid (PABA), octyl dimethyl PABA (Eusolex® 6007), and 4-methylbenzylidene camphor (Eusolex® 6300) were non-mutagenic (in the absence of light) and non-photomutagenic (in the presence of light). Dihydroxyacetone (DHA), used as an active ingredient in self-tanning lotions, slightly increased the number of revertants in Salmonella typhimurium TA100 and TA102 in the absence of light. However, the relevance of these effects is equivocal, since they occured at very high, cytotoxic concentrations (5000 μg/plate). Furthermore, these increases were not potentiated by light, thus demonstrating the non-photomutagenicity of DHA. In contrast, 7,12-dimethylbenz[a]anthracene (DMBA), which is non-mutagenic per se and is activated by external metabolizing systems (e.g., S9-mix) in the absence of light, was clearly mutagenic in Salmonella typhimurium TA98 and TA1537 in the presence of light (and the absence of S9-mix). Although the photomutagenic potency of DMBA, on a molar basis, was certainly lower than that of 8-MOP, the absolute mutagenic effects of DMBA in the respective bacterial strains were in a similar range under either S9-mix or photoactivation conditions. The strain specificity of the mutagenic effects were, however, different for either enzyme- or light-mediated mutagenicity. This indicates that different reactive intermediates are responsible for the mutagenicity in the tests using the two different activation systems. These results further suggest to use DMBA as a positive photomutagenic control compound alternatively to 8-MOP, since the latter is non- or only weakly photomutagenic in Salmonella typhimurium TA98 and TA1537. Furthermore, the usefulness and application of this photomutagenicity test system could be demonstrated for the testing of different photoabsorbing chemicals and cosmetic ingredients.

The frequency of chromosomal aberrations was evaluated in more than 500 liquidators of the Chernobyl accident. The ‘sarcophagus’ builders and the dosimetrists showed the highest frequency of aberrations per 100 cells: 3.24 ± 0.25 and 3.11 ± 0.43. For Chernobyl Atomic Power Station staff members the mean frequencies of aberrations per 100 cells was 2.37 ± 0.20. The mean yields of aberrations in the other groups was between 1.31 and 1.47 per 100 cells. If the mean frequencies of aberrations are converted into equivalent whole body doses, values between 136 and 414 mGy are obtained. Especially in the group of ‘sarcophagus’ builders, the yields of aberrations varied interindividually and corresponded to equivalent whole body doses of up to about 2 Gy.

In Taiwan, betel quid is a natural masticatory, which is composed of fresh green areca fruit, Piper betle and slaked lime paste. Areca fruit contains some alkaloids, of which arecoline is the major one. N-Nitrosoguvacoline (NG), one of the N-nitrosation products of arecoline, is the only one N-nitrosamine found in Taiwanese betel quid chewing saliva. The mutagenic studies in Ames Salmonella microsome test showed that crude alkaloid extracts of areca fruit and arecoline were active in Salmonella typhimurium TA100, and NG was weakly active in TA98 and TA100. The activities in both arecoline and NG decreased further in the presence of rat liver S9 mix. Nitrite was significantly consumed during the N-nitrosation of arecoline and sodium nitrite at acidic condition (pH 3), whereas the formation of NG was favored at neutral condition (pH 7). Crude phenolic extracts of leaf and inflorescence of Piper betle inhibited the formation of NG by blocking the nitrite. However, a high amount of crude phenolic extracts of areca fruit enhanced the formation of NG.

The alkaline comet assay (single cell gel electrophoresis assay) is a sensitive method for the detection of DNA damage. This paper describes the first application of this assay to plant cells for genotoxicological assessment. Germinating Vicia faba (field bean) seedlings were kept in water with either methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), mitomycin C (MMC), cycloheximide (CH), cadmium chloride (CdCl₂), potassium dichromate (K₂Cr₂O₇), or chromium trichloride (CrCl₃). Nuclei were isolated from the root cells and evaluated for the extent of DNA migration. With the exception of cycloheximide, all agents induced a significant increase in DNA migration. These results indicate that the comet assay may be a valuable tool for monitoring DNA damage in plant systems. However, there was a significant heterogeneity in the extent of DNA migration within and between seedlings, which may be intrinsic to the assay or indicative of sampling problems.