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First published on December 17, 2004; DOI: 10.1124/dmd.104.002444

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Received for publication September 21, 2004.
Revised December 15, 2004.
Accepted for publication December 16, 2004.

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

Koichi Haraguchi 1*, Nobuyuki Koga 2, Yoshihisa Kato 3

1 Daiichi College of Pharmaceutical Sciences 2 Nakamura Gakuen University 3 University of Shizuoka

* Address correspondence to: E-mail: ko-ichi{at}ka2.so-net.ne.jp

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, ip). The percentage contribution of major PCB residues in the liver five days after exposure indicated that non-planar 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. While 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.


Key words: cytochrome P450 catalyzed oxidations, GC/MS, halogenated hydrocarbons, metabolite indentification, metabolite kinetics, reactive metabolites


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Y. Kato, S.-i. Ikushiro, R. Takiguchi, K. Haraguchi, N. Koga, S. Uchida, T. Sakaki, S. Yamada, J. Kanno, and M. Degawa
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