Raj H G, Clearfield M S, Lotlikar P D
Carcinogenesis. 1984 Jul;5(7):879-84. doi: 10.1093/carcin/5.7.879.
Inhibition of microsome mediated aflatoxin B1 (AFB1) binding to exogenous or endogenous DNA by cytosolic glutathione (GSH) S-transferases is well established from our earlier studies. Correlation between inhibition of AFB1-DNA binding and AFB1-GSH conjugation in vitro using rat and hamster liver subcellular fractions is elucidated in this report. Even though hamster liver microsomes catalyzed AFB1 binding to exogenous DNA three times as much as the rat, hamster cytosol inhibited AFB1-DNA binding catalyzed by either microsomes severalfold more than the rat cytosol. AFB1-DNA binding is found to be inversely related to AFB1-GSH conjugation at all AFB1 concentrations (2-100 microM) studied. Presence of either styrene oxide or 3,3,3-trichloropropene oxide at 1 mM level diminished AFB1-GSH formation in vitro confirming some competition by these epoxides with AFB1-epoxide for cytosolic GSH S-transferases. In a reconstituted system with endogenous DNA, the ratio of AFB1-GSH to AFB1-DNA binding was found to be 10-15 times higher with the hamster in comparison with the rat indicating enhanced inactivation of the ultimate carcinogenic metabolite in the hamster. These results are discussed in relation to AFB1-DNA binding and AFB1 hepatocarcinogenicity in resistant and sensitive species.
我们早期的研究已充分证实，胞质谷胱甘肽（GSH）S-转移酶可抑制微粒体介导的黄曲霉毒素B1（AFB1）与外源性或内源性DNA的结合。本报告阐述了使用大鼠和仓鼠肝脏亚细胞组分在体外抑制AFB1-DNA结合与AFB1-GSH共轭之间的相关性。尽管仓鼠肝脏微粒体催化AFB1与外源性DNA的结合是大鼠的三倍，但仓鼠胞质溶胶对微粒体催化的AFB1-DNA结合的抑制作用比大鼠胞质溶胶强几倍。在所研究的所有AFB1浓度（2-100 microM）下，发现AFB1-DNA结合与AFB1-GSH共轭呈负相关。1 mM水平的环氧苯或1,1,1-三氯环氧丙烷的存在减少了体外AFB1-GSH的形成，证实了这些环氧化物与AFB1-环氧化物对胞质GSH S-转移酶存在一定竞争。在含有内源性DNA的重组系统中，发现仓鼠的AFB1-GSH与AFB1-DNA结合的比率比大鼠高10-15倍，表明仓鼠中最终致癌代谢物的失活增强。结合抗性和敏感物种中AFB1-DNA结合及AFB1肝癌致癌性对这些结果进行了讨论。
