Influences of inducers and inhibitors of the microsomal monooxygenase system on the alkylating intensity of dimethylnitrosamine in mice.

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.