title: Induction of EROD activity by 1-phenylimidazole and beta-naphthoflavone in rainbow trout cultured hepatocytes: a comparative study.
abstract: The classical pathway for induction of cytochrome P4501A (CYP1A) by xenobiotics is ligand binding to the aryl hydrocarbon receptor (AhR). However, several studies with mammalian cell systems point out a range of xenobiotics including imidazole derivatives, which are able to activate CYP1A through non-classical mechanisms. The objective of the present work is to compare induction of CYP1A (determined at the catalytic level as 7-ethoxyresorufin-O-deethylase, EROD) in rainbow trout (Oncorhynchus mykiss) hepatocytes by the prototypic AhR ligand, beta-naphthoflavone (betaNF), and by the imidazole derivative, 1-phenylimidazole (PIM). PIM was able to induce EROD activity although its potency was clearly lower than that of betaNF. In order to assess the relative importance of classical AhR ligand binding and alternative signaling pathways in CYP1A induction by PIM, co-exposure experiments with the partial AhR antagonist alpha-naphthoflavone (alphaNF) or with inhibitors of protein kinase C (staurosporine) and tyrosine kinases (genistein, herbimicine) were performed. alphaNF and herbimicin provoked a decrease of EROD induction both by betaNF and PIM, whereas staurosporine and genistein remained without effect. The overall similarities in the response of betaNF and PIM to the various inhibitors suggest that both compounds, in apparent contrast to the behaviour of some other imidazole derivatives, induce CYP1A following similar mechanisms.
authors.affiliation: Area of Toxicology, Faculty of Pharmacy, University of Seville, Professor García González 2, E-41012 Seville, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Jos
authors.forename: H
authors.initials: H
authors.lastname: Segner
authors.forename: B
authors.initials: B
authors.lastname: Herradón
authors.forename: G
authors.initials: G
authors.lastname: Repetto
authors.forename: J M
authors.initials: JM
authors.lastname: Navas
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects* / Q000378:metabolism; D004790:Enzyme Induction; D022781:Hepatocytes / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D008024:Ligands; D017686:Oncorhynchus mykiss; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019324:beta-Naphthoflavone / Q000494:pharmacology*
chemical_list: D007093:Imidazoles; D008024:Ligands; D018336:Receptors, Aryl Hydrocarbon; D019324:beta-Naphthoflavone; C037738:1-phenylimidazole; D019363:Cytochrome P-450 CYP1A1; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C