GLUCOCORTICOID-XENOBIOTIC INTERACTIONS - DEXAMETHASONE-MEDIATED POTENTIATION OF CYTOCHROME P4501A INDUCTION BY BETA-NAPHTHOFLAVONE IN A FISH HEPATOMA-CELL LINE (PLHC-1)
M. Celander et al., GLUCOCORTICOID-XENOBIOTIC INTERACTIONS - DEXAMETHASONE-MEDIATED POTENTIATION OF CYTOCHROME P4501A INDUCTION BY BETA-NAPHTHOFLAVONE IN A FISH HEPATOMA-CELL LINE (PLHC-1), Environmental toxicology and chemistry, 16(5), 1997, pp. 900-907
The induction of CYP1A by the polycyclic aromatic hydrocarbon (PAH)-ty
pe inducer beta-naphthoflavone (BNF) in the Poeciliopsis-lucida hepato
cellular carcinoma cell line (PLHC-1), and the effects of the glucocor
ticoid receptor (GR) agonist dexamethasone (DEX) on this response were
examined. Dose-response studies revealed that BNF is three orders of
magnitude less potent than the planar halogenated aromatic hydrocarbon
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as an inducer of the CYP1A
activity ethoxyresorufin-O-deethylase (EROD), and that the apparent e
fficacy for the induction by BNF is 50% of that obtained with TCDD. Ad
dition of 10 mu M DEX resulted In potentiation of CYP1A induction at a
ll doses bi. BNF tested. The degree of that potentiation of induction
of CYP1A protein levels and EROD activity differed substantially betwe
en doses of BNF and at different times of exposure. For example, the m
aximal degree of potentiation of EROD induction by DEX was 12-fold in
PLHC-1 cells treated with 0.1 mu M BNF 19-fold in cells treated with 1
mu M BNF, and 8-fold in cells treated with 10 mu M BNF These maximal
degrees of potentiation of EROD induction were obtained after 30 h wit
h 0.1 mu M BNF, 48 h with 1 mu M BNF and 72 h with 10 mu M BNF. These
results demonstrate interactions between GR and aryl hydrocarbon recep
tor pathways that could influence the response of fish to xenobiotic e
xposure.