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  • 1
    ISSN: 1432-0738
    Keywords: Aflatoxin B1 ; Parenchymal cells ; Nonparenchymal cells ; Mutagenicity ; DNA binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In vitro studies with rat liver parenchymal, Kupffer and endothelial cells isolated from male Sprague-Dawley rats were undertaken to investigate cell-specific bioactivation of aflatoxin B1, DNA binding and adduct formation. In the mutagenicity studies, using homogenates of all three separated liver cell populations (co-incubated with NADP+ and glucose-6-phosphate as cofactors for the cytochrome P-450 monooxygenase system) parenchymal, Kupffer and endothelial cells were able to activate aflatoxin B1 to a metabolite mutagenic to Salmonella typhimurium TA 98. In the case of nonparenchymal cells (i.e. Kupffer and endothelial cells) 10-fold higher concentrations of aflatoxin B1 had to be used to obtain a similar number of revertants to that observed with parenchymal cells. Induction studies with Aroclor 1254 led to a striking decrease in the activation of aflatoxin B1 in parenchymal cells, whereas nonparenchymal cells had a slightly enhanced metabolic activation capacity for aflatoxin B1. Metabolism studies with microsomes from induced and noninduced cells using testosterone as substrate revealed comparable results: after induction with Aroclor 1254, parenchymal cells showed a 60% decrease in the formation rate of 2α-hydroxytestosterone, whereas the formation rate of this metabolite remained unchanged in nonparenchymal cells; 2α-hydroxytestosterone is specifically formed by cytochrome P-450 IIC11, which also catalyses the activation of aflatoxin B1 to its epoxide. When freshly isolated, intact cells were incubated with tritiated aflatoxin B1, a dose-dependent aflatoxin B1 binding to DNA in parenchymal and nonparenchymal cells was observed. HPLC analysis of DNA acid hydrolysates of all three cell types showed the major adduct to be 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    International archives of occupational and environmental health 67 (1995), S. 35-39 
    ISSN: 1432-1246
    Keywords: Biomonitoring ; DNA damage Benzene ; Cigarette smoking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract DNA single strand breaks, including DNA adducts that lead to alkali-labile sites, were measured in peripheral mononuclear blood cells of 35 petrol pump attendants by alkaline filter elution. Blood samples from petrol pump attendants were taken on Monday and Friday. Additionally, DNA single strand breaks of smoking and non-smoking control persons were examined. For the smoking (n = 12) and the non-smoking controls (n = 20) a mean normalized elution rate of 1.49 ± 0.52 (mean value ± 95% confidence interval) and 1.32 ± 0.28, respectively, was obtained. The difference between smoking and non-smoking controls was not statistically significant (U test). An increase in DNA single strand breaks from Monday to Friday was detected for non-smoking petrol pump attendants with a daily working time of more than 4 h at the pump station. Their mean normalized elution rate increased from 1.08 on Monday to 1.89 on Friday. This difference was statistically significant (P 〈 0.05; Wilcoxon test for paired data), although the 95% confidence interval was large on Friday (0.43 on Monday; 1.23 on Friday). However, no significant increase was found for non-smoking petrol pump attendants who were on duty for less than 4 h per day at the pump station. No statistically significant increase in DNA single strand breaks could be detected for smoking petrol pump attendants whether they were pumping gasoline for more or for less than 4 h per day.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    International archives of occupational and environmental health 68 (1996), S. 141-146 
    ISSN: 1432-1246
    Keywords: Key words DNA strand breaks ; DNA adducts ; Biomonitoring ; Roofers ; Road paving workers ; Bitumen painters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The genotoxic effect of occupational exposure to bitumen-based products was determined by the extent of DNA strand breaks and alkali-labile sites of the DNA of peripheral mononuclear blood cells from seven roofers, 18 road paving workers, and nine bitumen painters. In order to evaluate short-term genotoxic effect the workers were investigated on Fridays and on Mondays after a weekend free of occupational exposure. The roofers (all cigarette smokers) showed a significantly (P 〈 0.002) 43% higher mean level of alkaline DNA strand breaks on Friday than did the ten smoking controls included in this study. Also, comparison of the individual levels of alkaline strand breaks on Mondays and on Fridays revealed a significant increase (P 〈 0.05, Wilcoxon test) during the work week. In the road paving workers and the bitumen painters no statistically significant difference in the mean levels of alkaline strand breaks could be found compared to controls either for the measurement on Mondays or for that on Fridays. However, interesting tendencies were observed. As in the group of roofers, the mean level of alkaline DNA strand breaks as well as the majority of the individual levels of alkaline strand breaks of road paving workers was higher on Fridays than on Mondays. In contrast, bitumen painters exhibited a relatively high level of alkaline DNA strand breaks on Mondays and a decreased mean level of strand breaks on Fridays. DNA adducts could be detected at a low level (up to 2.9 adducts per 109 bases) in 10 of 14 road paving workers and bitumen painters using the 32P-postlabelling assay. The number of DNA adducts correlated with the years spent in the present job. Road paving workers and bitumen painters showed only suggestive evidence for a possible genotoxic effect due to their occupational exposure. Because we cannot exclude the formation of DNA cross-links in these workers, a more detailed investigation of the hazard is urgently needed. For roofers, substantial genotoxic damage in peripheral mononuclear blood cells was observed in this study.
    Type of Medium: Electronic Resource
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