Ho L L, Jhee E C, Gopalan P, Tsuji K, Lotlikar P D
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA.
IARC Sci Publ. 1991(105):427-30.
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.
利用雄性费希尔大鼠和叙利亚仓鼠新鲜分离的肝细胞，研究了黄曲霉毒素B1（AFB1）与DNA的结合以及AFB1代谢过程中AFB1与谷胱甘肽的结合情况。尽管细胞色素P450和谷胱甘肽含量没有显著差异，但这两个物种肝细胞中AFB1（33 nM）的代谢存在明显差异。因此，大鼠肝细胞中AFB1与DNA的结合比仓鼠肝细胞高6倍，而仓鼠肝细胞中AFB1与谷胱甘肽的结合比大鼠肝细胞高12倍。添加0.5 mM马来酸二乙酯对大鼠没有显著影响，而在仓鼠肝细胞中，它使AFB1与DNA的结合增加了9倍，同时硫醇结合受到85%的抑制。环氧苯乙烷（1 mM）分别使大鼠和仓鼠肝细胞中AFB1与DNA的结合增加了50%和25倍，同时硫醇结合相应减少。溴化三乙基锡（50 microM）在大鼠肝细胞中使这两个过程都受到50%的抑制，而在仓鼠肝细胞中，它使AFB1与DNA的结合增加了9倍，同时硫醇结合减少。这些结果表明，谷胱甘肽S-转移酶在调节仓鼠肝细胞中AFB1与DNA的结合方面比在大鼠肝细胞中发挥着更重要的作用。
