Polychlorinated biphenyl-induced effects on metabolic enzymes, AP-1 binding, vitamin E, and oxidative stress in the rat liver

Environmental pollutants, such as polychlorinated biphenyls (PCBs), may ind uce drug metabolism and may be substrates for the induced metabolic enzymes . Both processes may lead to oxidative stress. The goal of this study was t o determine the influence of polychlorinated biphenyls, selected as inducer s and substrates of drug metabolism, on oxidative events within the liver o ver a 3-week time course. Male and female Sprague-Dawley rats received two ip injections per week of 4-chlorobiphenyl, 2,4,4'-trichlorobiphenyl, 3,4,5 -trichlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl (PCB 77), 2,2',4,4',5,5'- hexachlorobiphenyl (PCB 153), or both PCB 77 and 153 (100 mu mol/kg/injecti on) and were euthanized at the end of 1, 2, or 3 weeks. Hepatic cytochrome P450 1A1 (EROD) activity, DT-diaphorase activity, AP-1 DNA-binding activity , conjugated dienes, and a-tocopherol (vitamin E) as well as alpha -tocophe ryl quinone (oxidized vitamin E) were determined. While the lower chlorinat ed biphenyls (at these doses and times) showed little or no effect on these oxidative stress parameters, both CYP 1A1 and DT-diaphorase activities wer e significantly increased in both male and female rats receiving PCB 77, a ligand for the aryl hydrocarbon receptor. In addition, the DNA-binding acti vity of the transcription factor AP-1 was increased in rats treated with PC B 77 or PCB 153. Within the lipid fraction there was no significant increas e observed in conjugated diene concentrations, but there was a significant increase in alpha -tocopheryl quinone upon treatment with all PCBs tested. These data indicate that a-tocopheryl quinone may be a sensitive marker for PCB exposure and is possibly increased by a wide range of PCBs. (C) 2001 a cademic Press.