Guttenplan J B, Hutterer F, Garro A J
Mutat Res. 1976 Jun;35(3):415-22. doi: 10.1016/0027-5107(76)90203-7.
The relationship between microsomal dimethylnitrosamine (DMN) demethylase activity and the capacity of isolated hepatic microsomes to activate DMN to a mutagen was examined using microsomes from C57 and DBA/2 mice which had been exposed to three different types of microsomal enzyme inducers: phenobarbital, which induces cytochrome P-450, 3-methylcholanthrene, which induces cytochrome P-448, and the polychlorinated biphenyl, Aroclor 1254 which appears to induce both types of cytochromes. DNM induced mutagenesis was assayed by a Salmonella auxotroph reversion test. With the C57 mice all three inducers increased both the activity of microsomal DMN demethylase and the capacity of the microsomes to activate DMN mutagenicity. In each case, however, the increase in mutagenicity was disproportionately greater than the increase in DMN demethylase activity. This was particularly evident with microsomes prepared from Aroclor induced mice. Microsomes from 3-methylcholanthrene treated DBA/2 mice were not induced for DMN demethylase or the activation of DMN mutagenicity. In addition the capacity of Aroclor to function as an inducer was relatively poor in this strain. Both DMN demethylation and mutagenesis were inhibited by the addition of either SKF 525-A or benzo (a)pyrene to the reaction mixtures. Thus microsomal activation of DMN to a mutagen and DMN demethylase appear to involve both cytochromes P-450 and P-448.
利用来自C57和DBA/2小鼠的微粒体，研究了微粒体二甲基亚硝胺（DMN）脱甲基酶活性与分离的肝微粒体将DMN激活为诱变剂的能力之间的关系。这些小鼠已暴露于三种不同类型的微粒体酶诱导剂：诱导细胞色素P - 450的苯巴比妥、诱导细胞色素P - 448的3 - 甲基胆蒽，以及似乎能诱导这两种细胞色素的多氯联苯Aroclor 1254。通过鼠伤寒沙门氏菌营养缺陷型回复突变试验测定DNM诱导的诱变作用。对于C57小鼠，所有三种诱导剂均增加了微粒体DMN脱甲基酶的活性以及微粒体激活DMN致突变性的能力。然而，在每种情况下，诱变性的增加都比DMN脱甲基酶活性的增加大得多。这在由Aroclor诱导的小鼠制备的微粒体中尤为明显。用3 - 甲基胆蒽处理的DBA/2小鼠的微粒体未被诱导产生DMN脱甲基酶或激活DMN的致突变性。此外，Aroclor在该品系中作为诱导剂的功能相对较差。向反应混合物中添加SKF 525 - A或苯并（a）芘均可抑制DMN的脱甲基作用和诱变作用。因此，微粒体将DMN激活为诱变剂以及DMN脱甲基酶似乎都涉及细胞色素P - 450和P - 448。
