Properties of aryl hydrocarbon (benzo[alpha]pyrene) hydroxylase in lung microsomes of mice

The activity of aryl hydrocarbon hydroxylase (AHH) in the lung from C3H/He and DBA/2 strains of mice was apparently increased by the oral administration of benzo[alpha]pyrene, but the enzyme activity in the liver was not. Properties of AHH enzymes in the lung microsomes from mice treated intraperitoneally with 3-methylcholanthrene (induced enzymes) were compared with those treated with corn oil (constitutive enzymes). The two enzymes were similar in pH-activity curve and the apparent Km for NADPH or NADH, but differed in the apparent Km for benzo[alpha]pyrene; the value for the induced enzyme (6micron) being lower than that for the constitutive enzyme (25 micron). Both 5,6- and 7,8-benzoflavones and 2,2'-bipyridine inhibited the activity of the two enzymes similarly, but N-benzyl-N,alpha-dimethylphenethylamine hydrochloride and 2-diethylaminoethyl diphenylpropylacetate inhibited the activity of the constitutive enzyme more severely than that of the induced enzyme. Cyclohexene oxide, 1,1,1-trichloropropane oxide, and leupeptin inhibited the activity of the constitutive enzyme slightly, but enhanced the activity of the induced enzyme. The significance of these differences was discussed briefly in relation to the carcinogenicity of polycyclic hydrocarbons.