Abstract：
:The multidrug resistance (MDR) transporter is a phosphorylated glycoprotein (P-gp) that has been implicated in the efflux of a large variety of xenobiotics, thereby protecting vital organs. This study examines the hypothesis that the multidrug resistance transporter is involved in restricting the entry of polychlorinated biphenyls (PCBs) into the brain. Three test systems were used. First, the ATPase activity of the human P-gp was measured as an indicator of the interaction of PCBs with the MDR transporter. PCB congeners and metabolites included in the study were PCB 153, PCB 169, PCB 77, and the 4-hydroxy and 4,4'-dihydroxy metabolites of PCB 77. An increase in ATPase activity was observed for all the PCBs tested except the 4-hydroxy metabolite of PCB 77. Second, we studied the transport of (14)C-PCB 77 and (14)C-PCB153 in a cell-culture model using porcine kidney cells expressing the human MDR1 or the mouse mdr1a gene and compared it to the transport in control cells. No difference in directional transport due to P-gp was observed with either of the congeners in any of the cell lines. Finally, the distribution pattern of (14)C-PCB 77 in mdr1a knockout mice and genetically matched wild-type mice was measured. No significant differences in tissue distribution, especially in the brain tissue, were observed between wild-type and mdr1a knockout mice. These results suggest that some PCB congeners can bind to the MDR1 transporter; however, they may not be transported by it.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Tampal NM,Robertson LW,Srinivasan C,Ludewig Gdoi
10.1016/s0041-008x(02)00069-8subject
Has Abstractpub_date
2003-03-15 00:00:00pages
168-77issue
3eissn
0041-008Xissn
1096-0333pii
S0041008X02000698journal_volume
187pub_type
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journal_title：Toxicology and applied pharmacology
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