7,12-二甲基苯并[a]蒽在肝微粒体中的代谢途径。
Metabolic pathways of 7,12-dimethylbenz[a]anthracene in hepatic microsomes.
作者信息
Yang S K, Dower W V
出版信息
Proc Natl Acad Sci U S A. 1975 Jul;72(7):2601-5. doi: 10.1073/pnas.72.7.2601.
High pressure liquid chromatography has enabled quantitative analysis of the in vitro metabolism of 7,12-dimethylbenz[a]anthracene, 7-methyl-12-hydroxymethylbenz[a]anthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene, and 7,12-dihydroxymethylbenz[a]anthracene by 3-methylcholanthrene-induced and control rat liver microsomes. The following previously unrecognized metabolites have been tentatively identified: 5,6-dihydro-5,6-dihydroxy-7-methyl-12-hydroxymethylbenz[a]anthracene, 3-hydroxy-7,12-dihydrodihydroxymethylbenz[a]anthracene, 4-hydroxy-7,12-dihydrodihydroxymethylbenz[a]anthracene, and 8,9-dihydro-8,9-dihydroxy-7,12-dihydroxymethylbenz[a]anthracene. The epoxide hydratase inhibitor 1,2-epoxy-3,3,3-trichloropropane was found to eliminate all dihydrodiol formation and markedly inhibit the formation of several dimethylbenzanthracene metabolites. It is proposed that the tentatively identified 3-hydroxy and 4-hydroxy derivatives are formed by an enzymatic mechanism that does not involve epoxides as intermediates. The metabolic pathways of 7,12-dimethylbenz[a]anthracene in hepatic microsomal enzymes are proposed.
高压液相色谱法已能够对7,12-二甲基苯并[a]蒽、7-甲基-12-羟甲基苯并[a]蒽、7-羟甲基-12-甲基苯并[a]蒽和7,12-二羟甲基苯并[a]蒽在经3-甲基胆蒽诱导的大鼠肝微粒体及对照大鼠肝微粒体中的体外代谢进行定量分析。以下几种先前未被识别的代谢产物已被初步鉴定：5,6-二氢-5,6-二羟基-7-甲基-12-羟甲基苯并[a]蒽、3-羟基-7,12-二氢二羟甲基苯并[a]蒽、4-羟基-7,12-二氢二羟甲基苯并[a]蒽以及8,9-二氢-8,9-二羟基-7,12-二羟甲基苯并[a]蒽。发现环氧化物水合酶抑制剂1,2-环氧-3,3,3-三氯丙烷可消除所有二氢二醇的形成，并显著抑制几种二甲基苯并蒽代谢产物的形成。有人提出，初步鉴定出的3-羟基和4-羟基衍生物是通过一种不涉及环氧化物作为中间体的酶促机制形成的。文中还提出了7,12-二甲基苯并[a]蒽在肝微粒体酶中的代谢途径。
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