Genetic expression of aryl hydrocarbon hydroxylase induction. VI. Control of other aromatic hydrocarbon-inducible mono-oxygenase activities at or near the same genetic locus

When mice are administered aromatic hydrocarbons, the induction of aryl hydrocarbon (benzoa]pyrene) hydroxylase, p-nitroanisole O-demethylase, 7-ethoxycoumarin O-deethylase, and 3-methyl-4-methylaminoazobenzene N-demethylase activities—all membrane-bound mono-oxygenases having cytochrome P₄₅₀ associated with their active sites—is associated with the same genetic locus or with closely linked loci; we have previously proposed that this genetic region be designated the Ah locus for aromatic hydrocarbon responsiveness. Expression of these four inducible enzyme activities occurs as a single autosomal dominant trait in offspring from a genetic cross between inbred C57BL/6N and DBA/2N mice and from the appropriate backcrosses and intercross. There are no striking differences in relative thermolability or ontogenetic expression among these four closely linked aromatic hydrocarbon-induced mono-oxygenase activities. All four of these microsomal enzyme activities exist in two forms—one predominantly present in control or aromatic hydrocarbon-treated genetically nonresponsive mice and the other predominantly present in aromatic hydrocarbon-treated genetically responsive mice; the latter form is preferentially inhibited in vitro by such compounds as α-naphthoflavone. Whether a single induction-specific protein or a group of induction-specific proteins is associated with the Ah locus remains uncertain. The expression of aminopyrine N-demethylase, d-benzphetamine N-demethylase, NADPH-cytochrome c reductase, and NADPH-cytochrome P₄₅₀ reductase activities in aromatic hydrocarbon-treated genetically responsive and nonresponsive mice is not correlated with the Ah locus.