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Research ArticleArticle

COMPARATIVE METABOLISM OF POLYCHLORINATED BIPHENYLS AND TISSUE DISTRIBUTION OF PERSISTENT METABOLITES IN RATS, HAMSTERS, AND GUINEA PIGS

Koichi Haraguchi, Nobuyuki Koga and Yoshihisa Kato
Drug Metabolism and Disposition March 2005, 33 (3) 373-380; DOI: https://doi.org/10.1124/dmd.104.002444
Koichi Haraguchi
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Nobuyuki Koga
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Yoshihisa Kato
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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

  • 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.

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.104.002444.

  • 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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Drug Metabolism and Disposition: 33 (3)
Drug Metabolism and Disposition
Vol. 33, Issue 3
1 Mar 2005
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Research ArticleArticle

COMPARATIVE METABOLISM OF POLYCHLORINATED BIPHENYLS AND TISSUE DISTRIBUTION OF PERSISTENT METABOLITES IN RATS, HAMSTERS, AND GUINEA PIGS

Koichi Haraguchi, Nobuyuki Koga and Yoshihisa Kato
Drug Metabolism and Disposition March 1, 2005, 33 (3) 373-380; DOI: https://doi.org/10.1124/dmd.104.002444

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Research ArticleArticle

COMPARATIVE METABOLISM OF POLYCHLORINATED BIPHENYLS AND TISSUE DISTRIBUTION OF PERSISTENT METABOLITES IN RATS, HAMSTERS, AND GUINEA PIGS

Koichi Haraguchi, Nobuyuki Koga and Yoshihisa Kato
Drug Metabolism and Disposition March 1, 2005, 33 (3) 373-380; DOI: https://doi.org/10.1124/dmd.104.002444
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