Induction of hepatic drug-metabolizing enzymes in rats treated with 1-nitropyrene.

The inducing effects of 1-nitropyrene (1-NP) on the microsomal cytochrome P-450 system were studied in rats. Intraperitoneal administration of 1-NP led to increases in cytochrome P-450 content and aryl hydrocarbon hydroxylase, ethoxycoumarin, and ethoxyresorufin-O-deethylase activities. These increases were dose dependent. Cytochrome b5 content and aminopyrine and p-nitroanisole demethylase activities were not affected by treatment of rats with 1-NP. Substrate specificity, sensitivity to mixed-function oxidase inhibitors, and electrophoretic pattern of 1-NP-induced cytochrome(s) P-450 were compared to the major forms of cytochrome P-450 induced by phenobarbital and methylcholanthrene. Furthermore microsomes from 1-NP-induced rats showed greater ability to metabolize the chemical as compared with those from control animals; this result indicates that 1-NP induces a form(s) of cytochrome P-450 especially effective in the metabolism of the substance itself.