Abstract
The present study was performed to compare the metabolite profiles of polychlorinated biphenyls (PCBs) in the liver and serum of rats, hamsters, and guinea pigs after exposure to a PCB mixture, Kanechlor 500 (100 mg/kg, i.p.). The percentage of contribution of major PCB residues in the liver 5 days after exposure indicated that nonplanar PCBs with 2,4- or 2,3,4-chlorine substitution were more abundant in the liver in the order rats (43% of total PCBs) > hamsters (20%) > guinea pigs (11%), whereas coplanar PCBs with 4-, 3,4-, or 3,4,5-chlorine substitution were predominant in guinea pigs (61%), followed by hamsters and rats (both 26%). The hepatic concentrations of methylsulfonyl metabolites (MeSO2-CBs) were higher in the order guinea pigs > rats > hamsters. Whereas hamsters formed minute amounts of MeSO2-CBs from 2,5-dichloro-substituted PCBs, guinea pigs formed higher levels of meta-MeSO2-CBs derived from 2,3,6-trichloro-substituted PCBs. In contrast, the serum concentrations of phenolic PCBs were higher in the order hamsters > rats > guinea pigs. Metabolites were predominated by 4-OH-2,3,5,3′,4′-pentaCB (89% contribution) for rats, 3-OH-2,4,5,2′,4′-pentaCB (56%) for guinea pigs, and dihydroxylated metabolites (39%) for hamsters. The reduced elimination of coplanar PCBs and the specific distribution of MeSO2- and phenolic PCBs may have implications for the differences in sensitivity to PCB toxicity among rats, guinea pigs, and hamsters.
Footnotes
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The research was partially funded by a grant-in-aid for Scientific Research (C) (no. 16590101, K.H.; 15510058, Y.K.; and 14572119, N.K) from the Japan Society for the Promotion of Science and a Health and Labor Sciences Research Grant (Y.K.) from the Ministry of Health, Labor, and Welfare of Japan.
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.104.002444.
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ABBREVIATIONS: PCB, polychlorinated biphenyl; P450, cytochrome P450; OH, hydroxyl; CB, chlorobiphenyl; OH-PCB, hydroxylated PCB; MeSO2-CB, methylsulfonyl PCB; GC/MS, gas chromatography-mass spectrometry; GC/ECD, gas chromatography-electron capture detection; MC, 3-methylcholanthrene.
- Received September 21, 2004.
- Accepted December 16, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
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