Effect of enzyme inducers on metabolism of 1-nitropyrene in human hepatoma cell line HepG2.
We measured the response of HepG2 cells to the classic cytochrome (cyt.) P-450 inducers 3-methylcholanthrene (3-MC) and phenobarbital (PB), by evaluating oxidative and/or reductive metabolism of the nitroarenes, 1-NP and 1,6-dinitropyrene (1,6-DNP), in control and induced cells. In HepG2 cells, 3-MC induces ring-hydroxylation of 1-NP, whereas PB stimulates its nitroreduction. PB induces NADPH-cyt. c reductase, but does not affect other cytosolic and microsomal enzymes which contribute to 1-NP nitroreduction in these cells. However, PB-inducible nitroreductase activity seems to be associated primarily with cyt. P-450 isoenzymatic form(s), as indicated by the requirement for NADPH and the response to specific inhibitors such as alpha-naphthoflavone and CO.
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Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli, Italy.
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D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000378:metabolism*; D004790:Enzyme Induction; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism*; D008748:Methylcholanthrene / Q000494:pharmacology*; D009153:Mutagens / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology*; D011721:Pyrenes / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology; D014407:Tumor Cells, Cultured
D009153:Mutagens; D011721:Pyrenes; D008748:Methylcholanthrene; C033309:1,6-dinitropyrene; C032668:1-nitropyrene; D010634:Phenobarbital