Genetic expression of microsomal electron transport in mice. Different patterns of dependence of constitutive cytochrome P-450 reductase activity of pyridine nucleotide concentrations

Abstract

Cytochrome P-450 reductase and aryl hydrocarbon hydroxylase activities were investigated in hepatic microsomes from untreated C57BL/6J, DBA/2J, B6D2F1, and (B6D2) D2 mice. The dependence of the rate of P-450 reduction on the concentration of added pyridine nucleotide (NADPH or NADH) was biphasic in DBA/2J microsomes but monophasic in C57BL/6J microsomes. Analogous strain-specific patterns were observed when the dependence of the rate of benzpyrene hydroxylation on NADPH concentration was examined. In crosses between the two inbred strains and between B6D2F1 mice and DBA/2J mice, the biphasic pattern for both the reductase and the hydroxylase activities was found to co-segregate with the recessive allele for aromatic hydrocarbon responsiveness. These results might reflect an architectural difference between the microsomal electron transport systems of responsive and nonresponsive mice.