title: Dexamethasone-mediated potentiation of P450IA1 induction in H4IIEC3/T hepatoma cells is dependent on a time-consuming process and associated with induction of the Ah receptor.
abstract: The synergistic effect of dexamethasone (DEX) and polycyclic aromatic hydrocarbons on the induction of cytochrome P450IA1 (P450IA1) was examined in H4IIEC3/T Reuber hepatoma cells. P450IA1 activity was determined by the hydroxylation of benzo[a]pyrene (AHH) and deethylation of 7-ethoxyresorufin (EROD). The amount of Ah receptor, i.e. the specific cytosolic binding protein of 3-methylcholanthrene or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in H4IIEC3/T cells was characterized and quantitated by high performance gel filtration. Benz[a]anthracene and TCDD induced AHH and EROD activities, respectively, about 20-fold within 4 h. The increase was about 100-fold when cells were pretreated with DEX. The glucocorticoid alone induced P450IA1 activities 3-4 fold. DEX elicited half maximum AHH induction at a concentration of 20 nM in the presence or absence of benz[a]anthracene. Maximal potentiation of AHH induction required treatment with DEX for at least 32 h prior to the exposure to benz[a]anthracene. Treatment of H4IIEC3/T cells with DEX for 20 h caused a 2-3-fold increase in the amount of Ah receptor. The results suggest that the synergistic effect of DEX and polycyclic aromatic hydrocarbons on P450IA1 induction involves a time-consuming process which may consist of the synthesis or modification of a factor, possibly the Ah receptor.
authors.affiliation: GSF-Institute of Toxicology, Gesellschaft für Strahlen- und Umweltforschung, Neuherberg/München, F.R.G.
authors.forename: F J
authors.initials: FJ
authors.lastname: Wiebel
authors.forename: P
authors.initials: P
authors.lastname: Cikryt
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004790:Enzyme Induction; D006838:Hydrocarbons / Q000378:metabolism*; D006900:Hydroxylation; D007700:Kinetics; D008113:Liver Neoplasms / Q000201:enzymology*; D008748:Methylcholanthrene / Q000378:metabolism; D010078:Oxazines / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000378:metabolism*; D014316:Tritium; D014407:Tumor Cells, Cultured
chemical_list: D006838:Hydrocarbons; D010078:Oxazines; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D014316:Tritium; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; C007649:ethoxyresorufin; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System