ABSENCE OF INTERACTIONS ON HEPATIC RETENTION AND 7-ETHOXYRESORUFIN-O-DEETHYLATION ACTIVITY AFTER COADMINISTRATION OF 1,2,3,7,8-PENTACHLORODIBENZO-P-DIOXIN AND 2,4,5,2',4',5'-HEXACHLOROBIPHENYL

Interactions between 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PnCDD) and 2,4,5,2',4',5'-hexachlorobiphenyl (HxCB) on hepatic retention of PnCDD and on cytochrome P450 related enzyme activities were studied in male C57BL/6J mice. Animals received 8 nmol PnCDD/kg orally, alone or in combination with 1-416 mumol HxCB/kg. Co-administration of HxCB did not alter the hepatic retention of PnCDD or the 7-ethoxyresorufin-O-deethylation (EROD) activity induced by PnCDD as observed after 1 week. A small antagonistic effect on total cytochrome P450 content and 7-pentoxyresorufin-O-depentylation (PROD) activity was observed at a dose of 8 nmol PnCDD/kg and 1 mumol HxCB/kg. Furthermore, a significant induction of PROD activity by PnCDD was found. This was not expected, since PROD activity is considered to be a specific marker for CYP2b related enzyme activity and this type of cytochrome P450 is not induced by polychlorinated dibenzo-p-dioxins such as PnCDD. It is concluded that, under these short-term experimental conditions, no toxicokinetic basis was found to explain the antagonistic effects on hepatic cytochrome P450 related activities observed in the present study or in other studies.