Document bO0p6wQRy9366kR7b38ENRXkD

ri A,) MECHANISOMF'TOXICITOYF 'AUNIQUEPESTICIDE.t-: ETHYLPERFLUORDOCTANE SULFONAMIDE (NEPFOS)- Alff ITS METABOLITE PERFLUOROOCTANE (PFOS) TO ISOLATED RABBIT RENAL CORTICAL MITI:@.@CHONDRIA (RCM). T -J Cross and R G Schnel mann. Dept. Phys iol ./Pharmacol Col I Ve Med., University of Georgia, Athens, GA, NEPFOS is currently being evaluated as a pestr cide'for the red imported fire ant. Previous-:... studies from -this -laboratory-.showed that----U--*.@ early -effect of NEPFOS'and PFOS*on rabbit .proximal-tubules was -a concentration-deDendent';-j: (5-200 uM) increase in ouabain-insensitive piration (RESP). The goal of this study-was determine whether -the increased RESP resulted from uncoupling of oxidative phosphorylation PHOS). NEPFOS .(5-100 uM) -and-PFOS (0-5-'50 increased state 4 RESP of RCM -respiringon pyruvate/malate or succinate in the absence of a phosphate acceptor or in-the presence of oligomycin, an inhibitor of FOF1-ATPase. The effec+ of NEPFOS (200 uM), PFOS (100 uM), and the known protonophore FCCP (luM), on proton movement -by RCM was examined. Immediately+.onaddition, PFOS and,FCCP, but'not NEPFOS, dissipated the proton gradient. These retults show that PFOS acts as .a.-protonophoreand -:uncouplesOX PHOS by this --mechanism. The ',lackof :proton movement by EPFOS -suggests --@.tha-t--.NEPFOtS@:inayneed -tc) t>e @@getabol'l'zedto -VFDS -to -produce --r.,.ytoctiotxyi -and --I)X-PHOS. .,(Supportedby VMES,2 -Univ. I;eorg.ai). -g],kqC 141 5@7