Genetic Expression of Aryl Hydrocarbon Hydroxylase Induction

Intraperitoneal administration of aromatic hydrocarbons such as β-naphthoflavone or 3-methylcholanthrene stimulates hydroxylation activity toward carcinogens such as benzo[a]pyrene in the C57BL/6J inbred mouse strain, but this effect is virtually absent in the DBA/2J inbred mouse strain. Aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity was examined in vitro with various combinations of the solubilized NADPH-cytochrome P450 reductase, phospholipid, and cytochrome P448 or P450 fractions obtained from liver microsomes of β-naphthoflavone-treated mice of both strains. The results obtained indicate that the genetic difference in the inducible hydroxylase activity resides entirely in the fraction containing cytochromes P448 and P450. With respect to the reconstitution of d-benzphetamine N-demethylase and aryl hydrocarbon hydroxylase activities in vitro, each of these solubilized reductase, lipid, and cytochrome fractions—alone or in combination—from mouse liver can be interchanged successfully with those from rat liver, indicating a lack of species specificity in the hepatic monooxygenase system between mouse and rat.