Alterations of microsomal monooxygenase system and carcinogen metabolism by streptozotocin-induced diabetes in rats

The effects of diabetes on the liver microsomai monooxy-genaseenzymes and carcinogen metabolism have been studied in rats.Treatment with streptozotocin causes a marked enhancement inmicrosomai N-nitrosodimethylamine (NDMA) demethylase activity.The enhancement is due mainly to the induction of a high affinityNDMA demethylase (K_m, {small tilde}0.05 mM) which is accompaniedby the induction of a protein species with mol. wt. of 50 000.The treatment also induces aniline hydroxylase whose activityis in parallel with NDMA demethylase. Streptozotocin-induceddiabetes also increases the metabolism of N-nitrosomethyl-ethylaminebut not that of N-nitrosomethylaniline or N-nitrosomethylbenzylamine.On the other hand, diabetes decreases the metabolism of benzo[a]pyrene,benzphetamine, and ethylmorphine. The results suggest that diabetescauses an alteration of the composition of cytochrome P-450isozymes; the forms efficient in metabolizing NDMA are increasedwhile certain other forms of cytochrome P-450 are decreased.