Microsomal metabolism of dimethylnitrosamine and the cytochrome P-450 dependency of its activation to a mutagen.

Abstract

Summary Oxidative demethylation of the secondary carcinogen dimethylnitrosamine (DMN) by isolated mouse liver microsomes and the activation of DMN to a bacterial mutagen followed similar kinetics. The rates of demethylation and DMN activation increased following induction of the cytochrome P-450 mixed-function oxidase system by polychlorinated biphenyls. Both the oxidative demethylation and the activation of DMN to a mutagen were inhibited by carbon monoxide, and the inhibition was maximally reversed by monochromatic light at 450 nm. These observations indicate that both microsomal metabolism and activation of DMN to a mutagen are cytochrome P-450 dependent.