HIGH INDUCTION OF CYTOCHROME P4501A ACTIVITY WITHOUT CHANGES IN RETINOID AND THYROID-HORMONE LEVELS IN FLOUNDER (PLATICHTHYS-FLESUS) EXPOSED TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN

Oral doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were administ ered twice within 7 d (total concentration 0.01, 0.1, 1, 10, or 100 mu g TCDD/kg body weight) to flounder(Platichthys flesus). After 10 d of exposure, Rounder were sacrificed, and the effects of TCDD exposure o n hepatic microsomal total cytochrome P450 content, 7-ethoxyresorufin- O-deethylase (EROD) activity, and glutathione-S-transferase activity w ere examined. In addition, plasma and hepatic retinoid and plasma thyr oid hormone levels were analyzed. Overall a good correlation existed b etween the dose and liver concentrations of TCDD. However, only 0.75% of the total dose of TCDD was retained in the flounder liver. The TCDD caused a dose-related, statistically significant induction of the hep atic microsomal total cytochrome P450 content (4.4-fold; p < 0.001) an d associated EROD activity (27-fold; p < 0.001), without obvious chang es in body weight, liver weight, and condition factor. Total glutathio ne-S-transferase activity was not induced in livers of flounder expose d to TCDD. No TCDD-induced changes in liver retinoid, plasma retinol, and plasma thyroid hormone parameters were observed. These results ind icate that the flounder is an aryl hydrocarbon (Ah) receptor-responsiv e species with respect to CYP1A induction but not with respect to othe r mammalian Ah receptor-associated responses.