Genetic Regulation of Aryl Hydrocarbon Hydroxylase Induction

Abstract

Abstract In the inbred C57BL/6N mouse, aryl hydrocarbon hydroxylase induction by polycyclic hydrocarbons increases rapidly in the neonatal period; this response to these pharmacological, exogenous compounds does not appear in the DBA/2N, NZW/BLN, or NZB/BLN strains. The development of the constitutive hydroxylase activity in the neonatal period is the same in all four strains. Small differences in pH optima, substrate affinities, relative thermolability, or benzo[a]pyrene metabolism, which might have affected the enzyme assay, do not account for the large genetic difference in the response to polycyclic hydrocarbons. The hydroxylase induction by aromatic hydrocarbons is inherited as a simple autosomal dominant trait, designated the ah locus. In the individual mouse that is genetically responsive to polycyclic hydrocarbons, the hydroxylase activity is induced as an all-or-none phenomenon in all tissues which regularly contain the polycyclic hydrocarbon-inducible enzyme. The magnitude of induction of the hydroxylase is 4- to 5-fold in liver, and ranges from 5- to more than 80-fold in kidney, bowel, lung, and skin. The formation of a spectrally distinct carbon monoxide-binding cytochrome from liver microsomes is associated with the polycyclic hydrocarbon-inducible enzyme activity and is not seen in the liver of mice which are genetically nonresponsive to aromatic hydrocarbons. Phenobarbital induces the hepatic oxygenase to similar levels (i.e. about 2-fold) in all four strains.