Batardy-Gregoire M, Razzouk C, Agazzi-Leonard E, Mercier M, Poncelet F, Roberfroid M
Toxicol Lett. 1981 Mar;7(6):385-92. doi: 10.1016/0378-4274(81)90082-5.
Pretreatment of rat, hamster or mouse by 3-methylcholanthrene (3-MC) largely induces the liver microsomal N-hydroxylase activity. The same pretreatment given simultaneously with 2-acetylaminofluorene (2-AAF) inhibits the hepatocarcinogenicity in the rat but not in the hamster. The present report compared the in vivo and in vitro effects of 3-MC on liver microsomal N-hydroxylation and liver microsome-mediated mutagenicity of 2-AAF in hamster, rat and mouse. The induction of hamster or mouse liver microsomal N-hydroxylase activity correlated well with the increase in the microsome-mediated mutagenicity of 2-AAF. With rat, however, even though the N-hydroxylase activity is largely enhanced, microsome-mediated mutagenicity is significantly reduced after pretreatment with 3-MC. Such a reduction parallels a decrease in enzyme affinity. Added in vitro to the incubation medium, 3-MC (microM concentration) inhibits both the N-hydroxylase activity and the microsome-mediated mutagenicity of 2-AAF. Those data are discussed in relationship with the biological interactions between 3-MC and 2-AAF.
用3-甲基胆蒽（3-MC）对大鼠、仓鼠或小鼠进行预处理，可在很大程度上诱导肝微粒体N-羟化酶活性。与2-乙酰氨基芴（2-AAF）同时进行相同的预处理可抑制大鼠的肝癌发生，但对仓鼠无效。本报告比较了3-MC对仓鼠、大鼠和小鼠肝微粒体N-羟化作用以及肝微粒体介导的2-AAF致突变性的体内和体外效应。仓鼠或小鼠肝微粒体N-羟化酶活性的诱导与微粒体介导的2-AAF致突变性的增加密切相关。然而，对于大鼠，尽管N-羟化酶活性大幅增强，但用3-MC预处理后，微粒体介导的致突变性显著降低。这种降低与酶亲和力的下降平行。在体外向孵育培养基中添加3-MC（微摩尔浓度）可抑制2-AAF的N-羟化酶活性和微粒体介导的致突变性。这些数据结合3-MC与2-AAF之间的生物学相互作用进行了讨论。
