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
J. Dejongh et al., 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, Fundamental and applied toxicology, 25(2), 1995, pp. 264-270
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.