Toxicokinetic interactions between chlorinated aromatic hydrocarbons in the liver of the C57BL/6J mouse: I. Polychlorinated biphenyls (PCBs).
2,2',4,4',5,5'- (PCB 153), 2,3,3',4,4',5- (PCB 156) and 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169) were administered orally to three groups of C57BL/6J mice using single doses of 1.5-109.1 mg/kg. Two other groups of mice received binary mixtures of PCB 153 and 156 or PCB 153 and 169. The hepatic deposition, elimination, CYP1a and CYP2b dependent enzyme activities were studied during a 77-day period. Some interactive effects on hepatic deposition and elimination were observed, resulting in increased deposition and faster elimination. These effects were most pronounced for the PCBs 156 and 169. A potentiating effect on hepatic CYP1a dependent 7-ethoxyresorufin-O- deethylation (EROD) activity was observed for the combination of PCB 156 and 153. Based on the results from the present study and earlier studies, it is suggested that the potentiating effect on EROD activity might be caused by a mechanism that is governed by at least two factors. The first is a toxicokinetic modulation of hepatic retention. The second factor is probably an elevation of hepatic Ah receptor levels by PCB 153.
de Jongh
J
J
Research Institute of Toxicology, University of Utrecht, The Netherlands.
Wondergem
F
F
Seinen
W
W
Van den Berg
M
M
D000818:Animals; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D010088:Oxidoreductases / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics / Q000633:toxicity*
D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1