Appel K E, Schwarz M, Rickart R, Kunz W
J Cancer Res Clin Oncol. 1979 May 14;94(1):47-61. doi: 10.1007/BF00405349.
Male mice were pretreated with various drugs, which are known either induce or to inhibit cytochrome P 450 function. Five hours after the administration of 14C-dimethylnitrosamine (10 mg/kg) in pretreated and control mice, total and specific radioactivities of cellular macromolecules of the liver were determined. Various types of nucleic acids were extracted and hydrolyzed, and the bases and nucleotides separated by ion-exchange-chromatography. Radioactivity resulting from incorporation and alkylation was measured. Pretreatment of mice with the inducers phenobarbital and 3-Methylcholanthrene decreased the alkylation rates, while administration of the inhibitors SKF 525 A and CFT 1201 caused an increase. These results appear to contradict the accepted activation mechanism of nitrosamines if DMN demethylation as catalyzed by cyt. P 450 is influenced in the same way as other cyt. P 450 dependent reactions.
雄性小鼠用各种已知可诱导或抑制细胞色素P 450功能的药物进行预处理。在预处理小鼠和对照小鼠中给予14C-二甲基亚硝胺（10 mg/kg）5小时后，测定肝脏细胞大分子的总放射性和比放射性。提取并水解各种类型的核酸，通过离子交换色谱法分离碱基和核苷酸。测量掺入和烷基化产生的放射性。用诱导剂苯巴比妥和3-甲基胆蒽预处理小鼠可降低烷基化率，而给予抑制剂SKF 525 A和CFT 1201则导致烷基化率增加。如果细胞色素P 450催化的DMN去甲基化与其他细胞色素P 450依赖性反应受到相同方式的影响，那么这些结果似乎与公认的亚硝胺活化机制相矛盾。
