Enhancement by alloxan-induced diabetes of the rate of metabolic activation of three pyrolysate carcinogens via increase in the P-448-H content in rat liver

Abstract Heterocyclic amines are believed to be a causative factor in human cancer. To exert their carcinogenic effects, these chemicals, including Glu-P-1 + , IQ and MeIQx, require metabolic activation through their N-hydroxylations catalyzed by a 3-MC-inducible cytochrome P-450, P-448-H [2–4] . Although P-448-H is low, but detectable in untreated rats [2] , the factor regulating the endogenous expression of this form is still unclear. Diabetes is known to affect the levels of hepatic drug-metabolizing activities probably through alterations in the hormonal level and/or other biological components. These results, together with the high susceptibility of hepatic cytochrome P-450 to endocrine factors [5] , suggest the possibility that diabetes changes the levels of specific forms of cytochrome P-450 and has an effect on the activating capacity for carcinogens in the liver. Thus, we have studied the influence of diabetes on the level of pyrolysate activation.