查看更多>>摘要：Genotoxic agents can be detected by measuring DNA damage which result in the migration of DNA from single cells in agarose, using an electrophoretic field under alkaline conditions. The alkaline microgel electrophoresis technique was compared with in vitro structural chromosomal aberration (SCA) and mutation assays using V79 Chinese hamster lung cells and in vivo assays such as the bone marrow micronucleus assay in mice and a hepatocyte DNA repair assay in rats. Genotoxicants tested were those routinely used as positive control compounds in the various assays. In vitro assays included liver S9 for metabolic activation of cyclophosphamide (CP) for the SCA assay and benzo[a]pyrene (BP) for the mutation assay. A highly significant increase in DNA migration was induced by these agents under circumstances where a significant increase in DNA damage was detected using other endpoints. The alkaline microgel electrophoresis assay thus demonstrated the ability to detect DNA damage coinciding with the induction of DNA damage detected in these other assays for genotoxicity.
查看更多>>摘要：Capsaicin is the chemical responsible for the pungent, hot properties of Capsicum, a vegetable widely consumed in the diet of many countries in the world. In this work, the genotoxic capacity of capsaicin was studied in mouse during a 32-day treatment. We used the dosages of 1.46 and 1.94 mg/kg given by the i.p. route. Each week, the frequency of micronucleated normochromatic erythrocytes (MN-NE) and the ratio polychromatic/normochromatic erythrocytes (PE/NE) were scored. At the end of the experiment we also scored the frequency of sister chromatid exchanges (SCE). The results in the MN-NE analysis showed a genotoxic response with 1.94 mg/kg starting from day 16, while the 1.46 mg/kg dose produced a significant increase of MN-NE only at the 32nd day. The ratio PE/NE was only affected at the 32nd day with the high dose. Concerning the SCE frequency, the genotoxic effect was only observed with the highest dose. These results indicated that capsaicin is a genotoxicant, and due to the probable relation between an excessive consumption of Capsicum and an increase in gastric cancer, it is suggested that its consumption could be moderated until a definitive risk for humans is established.
查看更多>>摘要：The carbamate insecticides benfuracarb, carbosulfan and furathiocarb were investigated in the mouse bone marrow micronucleus assay to establish whether they show cytogenetic activity in vivo. Two doses of each substance were administered intraperitoneally to NMRI mice. All of the three substances led to a positive micronucleus response in polychromatic erythrocytes of the bone marrow at different expression times. While furathiocarb and carbosulfan showed similar patterns of the time-dependence of the micronucleus formation with maximum values after 72 h, benfuracarb exhibited a different behaviour with the maximum increase taking place within 24 h after substance application. In furathiocarb-treated animals the ratio of normochromatic to polychromatic erythrocytes showed a dose and time depending increase with the highest value obtained after 72 h in animals treated with the upper dose. The two yeast test systems Saccharomyces cerevisiae strains D7 and D61.M were applied in order to evaluate the genetic endpoints gene mutation, gene conversion and aneuploidy induction. None of the three insecticides had an influence on the frequencies of gene conversion and reverse mutation in the yeast S. cerevisiae D7 when tested with and without metabolic activation. In strain D61.M however benfuracarb and furathiocarb led to an increase of chromosome loss in the presence of the S9 metabolizing system.
查看更多>>摘要：Hemin and chlorophyllin are known to inhibit strongly the mutagenicity of benzo[a]pyrene in the Salmonella assay. To further investigate this phenomenon, a series of these pyrrole pigments including pure samples of Cu- and Fe-chlorins were tested for their potency to inhibit the mutagenicity of benzo[a]pyrene and its metabolites, benzo[a]pyrene-7,8-diol, benzo[a]pyrene-4,5-epoxide, and benzo[a]pyrene-7,8-diol-9, 10-epoxide. Hemin was the most potent among the pigments tested for these inhibitions. Both hemin and Cu-chlorin accelerated efficiently the degradation of benzo[a]pyrene-7,8-diol-9,10-epoxide, and this acceleration seemed to be the predominant mechanism by which these pigments inhibit,the overall mutagenicity of benzo[a]pyrene in Salmonella. Based on spectroscopic evidence, we speculate that a complex formation between hemin and benzo[a]pyrene-7,8-diol-9,10-epoxide takes place and that this complexing is the cause of the accelerated degradation.
查看更多>>摘要：Increased awareness of the role of environmental factors in carcinogenesis has led to an emphasis on preventing or minimizing exposure to genotoxicants. This is presently promoting the development of simple, rapid, cost-effective mutagenicity screening assays. We have developed a test system based on the well-known Salmonella mutagenicity assay. The lux genes, which permit cells to emit light through bioluminescence, were introduced into Salmonella typhimurium strain TA98. These bacteria were exposed for 48 h to chemicals or complex mixtures in 48-well microplates containing an appropriate liquid medium. Cells were subsequently centrifuged and resuspended in buffer, The final postexposure revertant biomass was then estimated using a microluminometer, Replication trials confirmed methodological reproducibility. Clear dose-response relationships were obtained with the direct frameshift mutagens 4NQO and 2NF. Mutagenicity threshold effect concentrations found for these compounds were comparable to those reported in the literature. Industrial effluents and environmental extracts (effluents, suspended solids) were also tested and results compared well with those of the SOS Chromotest. While further validation of this new adaptation of the Ames test will be required, it appears at this time that it could be well suited for routine screening of xenobiotics and environmental samples.
查看更多>>摘要：Garlic extract was evaluated in the mouse bone marrow micronucleus test for its possible protective effects against gamma-radiation-induced chromosomal damage. Together with this, biochemical assays were carried out to determine the changes in sulfhydryl content and glutathione S-transferase activities. Three doses of freshly prepared garlic extract (125, 250 and 500 mg/kg b.w.) were orally administered for 5 consecutive days, and the animals were irradiated 2 h after the final feeding. The results of the micronucleus test demonstrated that pre-treatment with garlic extract can lead to significant dose-related reductions in the frequencies of gamma-radiation-induced (2 Gy) micronucleated polychromatic erythrocytes. The anticlastogenic effect of garlic extract was observed against lower radiation doses of 0.5 and 1 Gy, but not 0.25 Gy. Significant increases in the sulfhydryl content and glutathione S-transferase activity were observed after either pre-treatment with garlic extract or irradiation. However, the irradiated garlic-extract pre-treated animals showed a significant reduction in sulfhydryl content and glutathione S-transferase activities.
查看更多>>摘要：The mutagenicity induced by soy sauce after reaction with 50 mM nitrite at pH 3, 37 degrees C, for 60 min in the presence of 1.25-10% ethanol was reduced in proportion to the ethanol concentration. The mutagenicity of soy sauce treated with nitrite was also reduced in the presence of commercial alcoholic beverages, Japanase sake, wine, 'shochu', whisky and brandy, but not beer, in proportion to the concentration. The mutagenicity of nitrite-treated tyramine, which is a major precursor of a mutagen in soy sauce treated with nitrite, was strongly reduced in the presence of ethanol, n-propanol or isopropanol and more strongly reduced in the presence of methanol, but was increased twofold in the presence of the sugars glucose or sucrose. The reduction of the mutagenicity of nitrite-treated tyramine required simultaneous treatment of tyramine with ethanol and nitrite. The mutagenicity of tyramine treated with nitrite was clearly reduced in the presence of shochu and whisky, similarly to ethanol. Analysis by high-performance liquid chromatography revealed that the reduction of the mutagenicity of nitrite-treated tyramine in the presence of ethanol resulted from the reduced production of mutagenic 3-diazotyramine from tyramine.
查看更多>>摘要：Chemicals used in the treatment of cancer include several that are potent mutagens in a range of in vitro and in vivo assays. For some, genetic effects have also been demonstrated in humans, detected as chromosomal aberrations in peripheral lymphocytes. Because (1) many of these agents are confirmed mutagens, (2) humans are exposed to them in relatively high doses, and (3) an increasing number of early cancer victims are surviving to reproductive age, it is important that information be available on the genetic and reproductive hazards associated with exposure to these agents. Chlorambucil and melphalan are structurally related chemicals that are included in our efforts to identify and assess such hazards among cancer chemotherapy agents. To date, both have been reported to induce specific locus mutations in germ cells of male mice (Russell et al., 1989; Russell et al., 1992b) and melphalan is one of very few chemicals shown to induce such mutations in spermatogonial stem cells. More recently, both chemicals were found to have strong reproductive effects in female mice (Bishop and Generoso, 1995, in preparation). In the present studies, these chemicals were tested for the induction of dominant lethal mutations and heritable translocations in male mice. Both chemicals were found to have reproductive effects attributable to cytotoxicity in specific male germ cell stages and to induce dominant lethal mutations and heritable translocations in postmeiotic germ cells, particularly in mid to early stage spermatids. Thus, relatively extensive data are now available for assessing the genetic and reproductive hazards that may result from therapeutic exposures to these chemicals.
查看更多>>摘要：Polychlorinated biphenyls (PCBs) are industrial chemicals which have been detected in fish, birds and humans. They are known to exert marked effects on the liver. They induce hepatocellular carcinoma in rats and birds, and are suspected of being carcinogenic to humans. To better understand the genotoxic effects of PCBs, we used P-32-postlabelling to investigate DNA adduct formation, after exposure to PCBs (Aroclor 1254 and 3,3',4,4'-tetrachlorobiphenyl), in primary cultures of fetal hepatocytes from two animal species and in a human cell line (Hep G2). We also studied the induction of 7-ethoxyresorufin-O-deethylase (EROD) in these PCB-treated cells. The three cell types used are known to express different cytochrome P450 families. The aim was to see whether a correlation could be established between EROD activity (a CYP1A1-related activity) and DNA adduct formation, DNA adducts were found in all three models after exposure to 50 mu M 3,3',4,4'-tetTachloiphenyl, The number of adducts was higher in quail hepatocytes (37 adducts per 10(9) nucleotides) than in rat hepatocytes or Hep G2 cells (20 adducts per 10(9) nucleotides in both cases). The major adduct was the same in all three cell types, but some adducts were found in only one or two species. These inter-species differences probably reflect metabolic differences leading to different ultimate carcinogens. Exposure to Aroclor 1254 failed to produce significant levels of DNA adducts, suggesting that pre-treated cells are required to magnify Aroclor 1254 metabolism. No correlation was found between adduct formation and the level of EROD induction.
查看更多>>摘要：Male Sprague-Dawley rats were intubated with 4 g/kg body weight of ethanol (in a 20%, v/v, water solution). Brain cells were analyzed for single-strand DNA breaks at various post-ethanol administration time points using an alkaline microgel electrophoresis assay. Results showed a significant increase in single-strand DNA breaks in brain cells that peaked at approx. 4 h and returned to control level within 6 h after ethanol administration.
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