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 doseof 1 nmol 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg. Sixother groups received single oral doses of 100, 300, or 1000µmol2,2',4,4',5,5'-hexachlorobiphenyl (HxCB)/kg, alone or in combinationwith 1 nmol/kg TCDD. Liver deposition of both compounds wasstudied at Day 3 after dosage. Hepatic CYP1A1 and CYP1A2 proteinlevels and related 7-ethoxyres-orufin-O-deethylation (EROD)and acetanilide 4-hydroxylation (ACOH) activities were alsostudied. A significant increase in the hepatic deposition ofTCDD was observed in all three mixed dose groups but TCDD didnot influence hepatic HxCB deposition. TCDD did increase bothCYP1A1 and CYP1A2 protein levels. In the HxCB-treated groups,CYP1A2 levels were also increased in a dose-dependent way butCYP1A1 levels were not increased. CYP1A2 activities (ACOH),but not protein levels, in the TCDD groups cotreated with HxCBwere higher than those in the group treated with TCDD alone.CYP1A1-dependent EROD activity and CYPlA2-dependent ACOH activitywere induced in all treated dose groups. It is concluded thatthe present results do not confirm a direct role of CYP1A2 inductionin the increase of hepatic TCDD levels by HxCB cotreatment inthe mixed HxCB/TCDD dose groups. However, in this aspect, thediscrepancy between CYP1A2 activities and protein levels remainsto be explained.