Aflatoxin B1-DNA binding and aflatoxin B1-glutathione conjugation with isolated hepatocytes from rats and hamsters.
Binding of aflatoxin B1 (AFB1) to DNA and AFB1-glutathione conjugation during the metabolism of AFB1 have been examined with freshly isolated hepatocytes from male Fischer rats and Syrian hamsters. Even though there was no significant difference in cytochrome P450 and glutathione contents, there were marked differences in the metabolism of AFB1 (33 nM) in hepatocytes from these two species. Thus, AFB1-DNA binding was six-fold higher in the rat than in hamster hepatocytes, whereas AFB1-glutathione conjugation was 12-fold higher in hamster than in rat hepatocytes. The addition of 0.5 mM diethylmaleate had no significant effect in rats, whereas its presence produced a nine-fold increase in AFB1-DNA binding with 85% inhibition of thiol conjugation in hamster hepatocytes. Styrene oxide (1 mM) produced 50% and 25-fold increases in AFB1-DNA binding in rat and hamster hepatocytes, respectively, with corresponding decreases in thiol conjugation. Triethyltin bromide (50 microM) inhibited both processes by 50% in rat hepatocytes, whereas it produced a nine-fold increase in AFB1-DNA binding with a concomitant decrease in thiol conjugation in hamster hepatocytes. These results suggest that glutathione S-transferases play a more significant role in modulating AFB1-DNA binding in hamster than in rat hepatocytes.
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Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA.
Jhee
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Gopalan
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Tsuji
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Lotlikar
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D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D004852:Epoxy Compounds / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008298:Maleates / Q000494:pharmacology; D051381:Rats; D013045:Species Specificity; D014267:Triethyltin Compounds / Q000494:pharmacology
D000348:Aflatoxins; D002273:Carcinogens; D004852:Epoxy Compounds; D008298:Maleates; D014267:Triethyltin Compounds; D004247:DNA; D016604:Aflatoxin B1; C013690:styrene oxide; C014476:diethyl maleate; D005978:Glutathione; C026405:bromotriethylstannane