Genetic association of increases in naphthalene, acetanilide, and biphenyl hydroxylations with inducible aryl hydrocarbon hydroxylase in mice

Abstract

The induction of four hepatic monooxygenase activities, naphthalene trans-1,2-dihy-drodiol formation, acetanilide 4-hydroxylase, biphenyl 4-hydroxylase, and biphenyl 2-hydroxylase, by polycyclic aromatic compounds is genetically associated with the induction of aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity and cytochrome P 1-450 in C57BL/6N and DBA/2N inbred mice and among progeny from the appropriate genetic crosses involving these two progenitor strains. These enzyme activities were studied with respect to (i) preferential inhibition by metyrapone, α-naphthoflavone, or Tween 80 in vitro; (ii) use of the microsomal inducers 3-methylcholanthrene, β-naphthoflavone, 2,3,7,8-tetrachlorodibenzo- p-dioxin, or phenobarbital; (iii) apparent K m values; and (iv) heat inactivation. Several lines of evidence suggest that aromatic hydrocarbon-induced naphthalene monooxygenase, acetanilide 4-hydroxylase, biphenyl 4-hydroxylase, and biphenyl 2-hydroxylase activities are, like the induced aryl hydrocarbon hydroxylase activity, associated with cytochrome(s) P 1-450 and that the basal activities of the first three of these enzymes are, like basal aryl hydrocarbon hydroxylase activity, associated with one (or more) forms of cytochrome P-450 other than cytochrome(s) P 1-450. On the other hand, the basal biphenyl 2-hydroxylase activity in mouse liver appears to be associated solely with cytochrome(s) P 1-450; this finding differs from all other basal monooxygenase activities associated with the Ah locus and studied thus far in a similar manner.