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.
Belisario
M A
MA
Istituto di Biochimica Cellulare e Molecolare, II Facoltà di Medicina e Chirurgia, Napoli, Italy.
Borgia
R
R
Pecce
R
R
de Lorenzo
F
F
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D010634:Phenobarbital / Q000494:pharmacology; D011721:Pyrenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011721:Pyrenes; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C032668:1-nitropyrene; D010634:Phenobarbital