Effect of enzyme inducers on metabolism of 1-nitropyrene in human hepatoma cell line HepG2.

Abstract

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.

• Authors: M A Belisario, A R Arena, R Pecce, R Borgia, N Staiano, F De Lorenzo
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 78 Issue 3 Pg. 253-68 ( 1991) ISSN: 0009-2797 [Print] Ireland
• PMID: 1649010 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Mutagens
• Pyrenes
• Methylcholanthrene
• 1,6-dinitropyrene
• 1-nitropyrene
• Phenobarbital

Topics

• Carcinoma, Hepatocellular (enzymology, metabolism)
• Enzyme Induction
• Humans
• Liver Neoplasms (enzymology, metabolism)
• Methylcholanthrene (pharmacology)
• Mutagens (metabolism)
• Phenobarbital (pharmacology)
• Pyrenes (metabolism)
• Subcellular Fractions (enzymology)
• Tumor Cells, Cultured