Comparisons of hepatic and renal cytochromes P-450-dependent monooxygenases from fuzzy and Sprague-Dawley rats.

The differences in monooxygenase activities between the fuzzy rat, a variant of the hairless rat, and the Sprague-Dawley rat were examined. Benzo(a)pyrene hydroxylase and benzphetamine N-demethylase activities and cytochrome P-450 contents were significantly lower in the livers of fuzzy rats than in the livers of the Sprague-Dawley rats. The hydroxylase activity in the kidneys of the two strains were not significantly different from each other. In comparison to the Sprague-Dawley rats, the induction of these enzymic activities by phenobarbital and 3-methylcholanthrene were of a lesser magnitude in the fuzzy rats, indicating that regulation of the hepatic monooxygenases differed in the two strains. Immunoblot data showed that cross-reactivity between antirat P-450IIB1 and microsomal protein from phenobarbital-treated rats appeared to be lower in the fuzzy rat when compared with the Sprague-Dawley rat. These differences in the constitutive enzymes and the differences in the induction of hepatic monooxygenases between the two strains of rats may be important determinants in studies involving metabolism of drugs and other chemicals following cutaneous exposure.