Effects on hepatic microsomal N- and C-oxygenation of aromatic amines by in vivo corticosteroid or aminofluorene treatment, diet, or stress.

Various environmental, endocrine, and inherent conditions, which enhance the tumor-inducing capacity of carcinogenic aromatic amines, are associated with an increased N-oxygenation of these compounds in vivo. The impairment of proteinsynthesizing functions of liver ribosomes by reactive metabolites of the carcinogenic amines is, to a certain extent, correlated with these functions. Here the effect of similar conditions on microsomal N-oxygenation and C-oxygenation in vitro was studied, using N-oxide formation and N-demethylation of N,~N-dimethylaniline as test reactions. Increased microsomal N-oxygenation, and to a considerably smaller extent N-demethylation was obtained by in vivo treatment with corticosteroid or 2-aminofluorene. Vitamin E depletion, protein deficiency, or stress caused an increase in N-oxygenation accompanied by decreased N-demethylation. These conditions thus gave rise to an increase in the N-oxygenation/C-oxygenation ratio. Guinea pig liver microsomes showed a higher N-demethylating capacity and a lower N-oxygenation than did rat liver microsomes. The N-oxygenation of N,N-dimethylaniline by liver microsomes thus seems to be well correlated with the tumor-inducing properties and ribosome-impairing capacity of carcinogenic aromatic amines under various in vivo conditions.