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

Chem Biol Interact. 1990;76(3):307-20. doi: 10.1016/0009-2797(90)90098-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzo(a)pyrene / metabolism
  • Carcinoma, Hepatocellular / enzymology*
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Cytosol / metabolism
  • Dexamethasone / pharmacology*
  • Enzyme Induction
  • Hydrocarbons / metabolism*
  • Hydroxylation
  • Kinetics
  • Liver Neoplasms / enzymology*
  • Methylcholanthrene / metabolism
  • Oxazines / metabolism
  • Polychlorinated Dibenzodioxins / metabolism
  • Receptors, Aryl Hydrocarbon
  • Receptors, Drug / metabolism*
  • Tritium
  • Tumor Cells, Cultured


  • Hydrocarbons
  • Oxazines
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon
  • Receptors, Drug
  • Tritium
  • Benzo(a)pyrene
  • Methylcholanthrene
  • ethoxyresorufin
  • Dexamethasone
  • Cytochrome P-450 Enzyme System