Characterization of the induction of rat hepatic microsomal drug-metabolizing enzymes by 1-nitropyrene metabolites, 1-aminopyrene and N-acetylaminopyrene.
The effect of 1-aminopyrene (1-AP) and N-acetylaminopyrene (1-NAAP) on rat hepatic microsomal monooxygenase system was investigated. Both drugs increased the total content of cytochrome P-450 (cyt. P-450). The substrate specificity and the electrophoretic pattern of 1-AP and 1-NAAP induced cytochrome(s) were compared with those of the major forms of cyt. P-450 induced by 3-methylcholanthrene (3-MC) and phenobarbital (PB). The results suggest that the form of cyt. P-450 induced by 1-AP and 1-NAAP resembles that one induced by 3-MC. Furthermore the abilities of liver microsomes from control or differently induced rats to ring hydroxylate and to activate 1-nitropyrene (1-NP) metabolites to species mutagenic for bacteria were compared. It was observed that: (1) 1-NAAP is a good substrate for microsome-mediated ring hydroxylation, whereas 1-AP is oxygenated only at a low extent; (2) 3-MC, 1-AP and 1-NAAP-stimulated microsomes are more active than control or PB-ones to ring hydroxylate 1-NAAP. As phenolic derivatives of 1-NAAP show high mutagenic activity, these results indicate that 1-AP and 1-NAAP induce toxification pathways of 1-NP in similar way, even if in less extent, as compared to 3-MC.
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Dipartimento di Biochimica e Biotechnologie Hediche, II Facoltá di Medicina e Chirurgia, Università degli Studi di Napoli, Italy.
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D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009153:Mutagens / Q000378:metabolism; D011721:Pyrenes / Q000378:metabolism* / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
D009153:Mutagens; D011721:Pyrenes; C060348:N-acetyl-1-aminopyrene; D003577:Cytochrome P-450 Enzyme System; C004482:1-aminopyrene; C032668:1-nitropyrene