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.
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.
Wiebel
F J
FJ
GSF-Institute of Toxicology, Gesellschaft für Strahlen- und Umweltforschung, Neuherberg/München, F.R.G.
Cikryt
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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
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