大肠粘膜细胞色素P450在致癌剂活化中的作用及其诱导和抑制
ROLE OF COLON MUCOSA CYTOCHROME P450 IN ACTIVATION OF CARCINOGEN AND THEIR INDUCTION AND INHIBITION
-
摘要: 本文研究了大肠粘膜细胞和肝细胞微粒体酶系对专一性致大肠癌化合物—二甲基肼(DMH)的代谢活性。实验证明,大肠粘膜细胞如同肝细胞一样,存在依赖细胞色素P450的混合功能氧化酶,能催化DMH的羟化反应.使之转变成具直接致癌活性的终致癌物,其羟化活性大约相当于肝的79.5%。大肠粘膜细胞对DMH的羟化活性及细胞色素P450含量,能被苯巴比妥钠所诱导,如给动物以维生素E,则两者同时降低。文中强调了大肠粘膜细胞色素P450在DMH代谢转变中的重要作用,并讨论了维生素E在预防大肠化学致癌过程中的意义。Abstract: The data presented in this report indicate that rat colon mucosa microsome contain a competent mixed function oxidase system depended on cytochrome P450. The colon enzymatic system catalyze the hydroxylation of the model colon carcinogen 1, 2—dimethylhydrazine(DMH). DMH is hydroxylated by colon system at rate 79.5% of the rate catalyzed by liver system. The colon system's hydroxylation activity and cytochrome P450 content can he induced by pretreatment with phenobarbital and can be inhibited by pretreatment with vitamin E. The experiment suggests important role of colon mucosa cytoehrome P450 in activation of carcinogen and possibility of vitamin E in protection of large bowel chemical carcinogenesis.