INDUCTION OF CYTOCHROME-P450 ISOENZYMES AFTER TOXICOKINETIC INTERACTIONS BETWEEN 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN AND 2,2',4,4',5,5'-HEXACHLOROBIPHENYL IN THE LIVER OF THE MOUSE

One group of male C57BL/6J mice received a single oral dose of 1 nmol 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg. Six other groups receiv ed single oral doses of 100, 300, or 1000 mu mol 2,2',4,4',5,5'-hexach lorobiphenyl (HxCB)/kg, alone or in combination with 1 nmol/kg TCDD. L iver deposition of both compounds was studied at Day 3 after dosage. H epatic CYP1A1 and CYP1A2 protein levels and related 7-ethoxyresorufin- O-deethylation (EROD) and acetanilide 4-hydroxylation (ACOH) activitie s were also studied. A significant increase in the hepatic deposition of TCDD was observed in all three mixed dose groups but TCDD did not i nfluence hepatic HxCB deposition. TCDD did increase both CYP1A1 and CY P1A2 protein levels. In the HxCB-treated groups, CYP1A2 levels were al so increased in a dose-dependent way but CYP1A1 levels were not increa sed. CYP1A2 activities (ACOH), but not protein levels, in the TCDD gro ups cotreated with HxCB were higher than those in the group treated wi th TCDD alone. CYP1A1-dependent EROD activity and CYP1A2-dependent ACO H activity were induced in all treated dose groups. It is concluded th at the present results do not confirm a direct role of CYP1A2 inductio n in the increase of hepatic TCDD levels by HxCB cotreatment in the mi xed HxCB/TCDD dose groups. However, in this aspect, the discrepancy be tween CYP1A2 activities and protein levels remains to be explained. (C ) 1995 Society of Toxicology.