Document EmjpELLw4LbZ8bXrdwEKeo8ng

< 7 -i MECHANISM OF TOXICITY OF A UNIQUE PESTICIDE ETHYLPERFLUOROOCTANE SULFONAMIDE (NEPFOS), Nft\. ITS METABOLITE PERFLUOROOCTANE SULFONAMIDE (PFOS) TO ISOLATED RABBIT RENAL CORTICAL KITO-; CHONDRIA (RCM). T J Cross and R G SchnelliL: m a n n . Dept. Physiol./Pharmacol., Coll- Vet^ Med., University of Georgia, Athens, GA,, NEPFOS is currently being evaluated as a pestij- cide for the red imported fire ant. * Previous studies from this Iaboratory* showed that * early effect of NEPFOS and PFOS on rabbit renal& proximal tubules was- a concentration-dependents (5-200 uM) increase in ouabain-insensitive res piration (RESP). The goal of this study was tn determine whether the increased RESP resulted - from uncoupling of oxidative phosphorylation (OX PHOS). NEPFOS (5-100 uM) and PFOS (0.5-50 uM) increased state 4 RESP of RCM respiring on pyru* vate/malate or succinate in the absence of * phosphate acceptor or in the presence of oligo* mycin, an inhibitor of FOFl-ATPase. The effec* of NEPFOS (200 uM), PFOS (100 uM), and the known protonophore FCCP (luM), on proton movement by RCM was examined. Immediately on addition, PF05 andrFCCP, but not NEPFOS, .dissipated the proton gradient. These results show that PFOS acts as a protonophore and uncouples OX PHOS by this mechanism. The lack of proton movement by NEPFOS suggests that NEPFOS m a y need to be ^metabolized to ^FOS to produce cytotoxicity anc uncoupling ^of X)X PHOS. -(Supported by VMES, tJniv. "Georgia). . M S T W T fteoM SlTHetriuG. .iW i