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3, 3 ,4, 4 ,5 -Pentachlorobiphenyl Inhibits Drug Efflux Through P-Glycoprotein in KB-3 Cells Expressing Mutant Human P-Glycoprotein

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Author(s): Fujise Hiroshi | Sasawatari Shigemi | Annoura Takeshi | Ikeda Teruo | Ueda Kazumitsu

Journal: Journal of Biomedicine and Biotechnology
ISSN 1110-7243

Volume: 2004;
Issue: 3;
Start page: 137;
Date: 2004;
Original page

ABSTRACT
The effects on the drug efflux of 3, 3 ′ ,4, 4 ′ ,5 -pentachlorobiphenyl (PCB-126), the most toxic of all coplanar polychlorinated biphenyls (Co-PCBs), were examined in KB-3 cells expressing human wild-type and mutant P-glycoprotein in which the 61st amino acid was substituted for serine or phenylalanine ( KB3-Phe 61 ). In the cells expressing P-glycoproteins, accumulations of vinblastine and colchicine decreased form 85% to 92% and from 62% to 91%, respectively, and the drug tolerances for these chemicals were increased. In KB3-Phe 61 , the decreases in drug accumulation were inhibited by adding PCB-126 in a way similar to that with cyclosporine A: by adding 1 μ M PCB-126, the accumulations of vinblastine and colchicine increased up to 3.3- and 2.3-fold, respectively. It is suggested that PCB-126 decreased the drug efflux by inhibiting the P-glycoprotein in KB3-Phe 61 . Since there were various P-glycoproteins and many congeners of Co-PCBs, this inhibition has to be considered a new cause of the toxic effects of Co-PCBs.
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