Differential sensitivity of hepatic microsomal aryl hydrocarbon hydroxylase to the inhibitory effect of SKF 525-A in rats of varying age, hormonal- and drug-induced status.

The inhibition of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) activity by SKF 525-A in vitro was studied in hepatic microsomes from rats of varying age, sex hormone status, and drug treatment. The concentration of SKF 525-A required to produce a 50% inhibition of AHH activity, the IC50, was determined for the various microsomal preparations. Microsomes from adult female and immature rats exhibited a similar sensitivity to SKF 525-A. However, microsomes from adult male rats were significantly more sensitive to the inhibitory effect of the drug. AHH activity from pseudohermaphroditic male rats was found to have the same sensitivity to SKF 525-A as in the female littermates. Microsomes obtained from adult rats that had been pretreated with various cytochrome P-450 inducing agents yielded significantly different IC50 values from untreated controls. These differences in IC50 values indicated that the predominant form(s) of cytochrome P-450 that hydroxylate benzo(a)pyrene varied with the age, hormonal, and induced status of the animal.