Influence of Drugs on Activation and Inactivation of Hepatocarcinogenic Nitrosamines

Abstract
The alkylation of liver macromolecules following in vivo administration of dimethylnitrosamine (DMN) was diminished after phenobarbital or 3-methylcholanthrene induction of the microsomal monooxygenase system, but increased after SKF 525 A pretreatment. Determination of CH2O and CH3 + formation in microsomal incubation systems revealed the same results for low DMN concentrations. An interpretation is given on the basis of spectrophotometric data and electron spinresonance (EPR) measurements, by proposing that metabolic inactivation of nitrosamines is catalysed by a reduction process in which cyt. P 450 seems to be involved.