Microsomal Metabolism of Dimethylnitrosamine and the Cytochrome P-450 Dependency of Its Activation to a Mutagen

Oxidative demethylation of the secondary carcinogen dimethylnitrosamine (DMN) by isolated mouse liver micro-somes 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.