Metabolic activation of dimethylnitrosamine to mutagens: role of cytochromes P-450 and P-448.

Pretreatment of hamsters with phenobarbitone, 3-methylcholanthrene and Arochlor 1254 induced the hepatic microsomal mixed function oxidases, yet decrease the efficiency of activation of dimethylnitrosamine (DMN) to intermediates mutagenic to the Salmonella typhimurium strain TA-100. Furthermore, no correlation was obtained between cytochrome P-450 content, microsomal demethylation of DMN and its activation to mutagens. These results indicate that the demethylation of DMN by the mixed-function oxidases is not the rate-limiting step in the metabolic activation of the carcinogen to mutagen(s), and that other microsomal or soluble enzymes may be involved.