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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 ( ${\text{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 ${\text{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 $\mu$ 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 ${\text{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.

journal of biomedicine and biotechnology

<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="$3,3',4,4',5$" id="E1"><mml:mrow><mml:mn>3</mml:mn><mml:mo>,</mml:mo><mml:msup><mml:mn>3</mml:mn><mml:mo>′</mml:mo></mml:msup><mml:mo>,</mml:mo><mml:mn>4</mml:mn><mml:mo>,</mml:mo><mml:msup><mml:mn>4</mml:mn><mml:mo>′</mml:mo></mml:msup><mml:mo>,</mml:mo><mml:mn>5</mml:mn></mml:mrow></mml:math>-Pentachlorobiphenyl Inhibits Drug Efflux Through P-Glycoprotein in KB-3 Cells Expressing Mutant Human P-Glycoprotein

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