Darby N J, Burnet F R, Lodola A
Biochem Pharmacol. 1985 Aug 1;34(15):2669-74. doi: 10.1016/0006-2952(85)90565-9.
2AAF is a potent inducer of cytochrome P-450 in the chick embryo liver. The induction has been characterized with respect to a range of monooxygenase activities and the regiospecificity of 2AAF hydroxylation. Similarities to the response elicited by both PB and 3MC were noted. 2AAF was rapidly deacetylated by hepatic microsomes prepared from control animals to 2AF, an inhibitor of monooxygenase activity. Metabolites generated in vivo and carried over in vitro might have therefore interfered with the subsequent kinetic analysis. In general terms induction of a unique cytochrome P-450 subform(s) could not be attributed to 2AAF in the chick embryo. The data is discussed with respect to the reported resistance of avian species to the hepatocarcinogenic effects of 2AAF. Two possibilities are highlighted, a diversion of 2AAF to ring hydroxylated metabolites and/or deacetylation of 2AAF. Both effects could reduce carcinogenicity by decreasing the concentration of proximate carcinogen and/or promoter(s).
2-乙酰氨基芴(2AAF)是鸡胚肝脏中细胞色素P-450的强效诱导剂。已对一系列单加氧酶活性以及2AAF羟基化的区域特异性进行了该诱导作用的表征。注意到其与苯巴比妥(PB)和3-甲基胆蒽(3MC)引发的反应有相似之处。2AAF被对照动物制备的肝微粒体迅速脱乙酰化为2-氨基芴(2AF),一种单加氧酶活性抑制剂。因此,体内产生并在体外残留的代谢产物可能干扰了后续的动力学分析。总体而言,在鸡胚中,独特的细胞色素P-450亚型的诱导不能归因于2AAF。结合所报道的鸟类对2AAF致癌作用的抗性对该数据进行了讨论。强调了两种可能性,2AAF转向环羟基化代谢产物和/或2AAF的脱乙酰化。这两种效应都可以通过降低近端致癌物和/或启动子的浓度来降低致癌性。