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 induce drug metabolism and may be substrates for the induced metabolic enzymes. Both processes may lead to oxidative stress. The goal of this study was to determine the influence of polychlorinated biphenyls, selected as inducers and substrates of drug metabolism, on oxidative events within the liver over 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 micromol/kg/injection) 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 alpha-tocopherol (vitamin E) as well as alpha-tocopheryl quinone (oxidized vitamin E) were determined. While the lower chlorinated biphenyls (at these doses and times) showed little or no effect on these oxidative stress parameters, both CYP 1A1 and DT-diaphorase activities were significantly increased in both male and female rats receiving PCB 77, a ligand for the aryl hydrocarbon receptor. In addition, the DNA-binding activity of the transcription factor AP-1 was increased in rats treated with PCB 77 or PCB 153. Within the lipid fraction there was no significant increase 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 alpha-tocopheryl quinone may be a sensitive marker for PCB exposure and is possibly increased by a wide range of PCBs.
Twaroski
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Graduate Center for Toxicology, University of Kentucky, 306 Health Sciences Research Building, Lexington, KY 40536-0305, USA.
O'Brien
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Larmonier
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Glauert
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Robertson
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D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004785:Environmental Pollutants / Q000494:pharmacology; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology
D004785:Environmental Pollutants; D018808:Transcription Factor AP-1; D014810:Vitamin E; C002421:tocopherylquinone; D004247:DNA; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; D016660:NAD(P)H Dehydrogenase (Quinone); C028451:3,4,3',4'-tetrachlorobiphenyl; C014024:2,4,5,2',4',5'-hexachlorobiphenyl