Document DG70YkDvobdKaKy7xd6LnLedO

Afm 6- o w MECHANISM OF TOXICITY OF A UNIQUE PESTICIDE:m ETHYLPERFLUOROOCTANE SULFONAMIDE (NEPFOS), A . ITS METABOLITE PERFLUOROOCTANE SULFONAMIDE (PFOS) TO ISOLATED RABBIT RENAL CORTICAL MIKK. i CHONDRIA (RCM). T J Cross and R G Schnell*mann. Dept. Physiol./Pharmacol., Coll. Vet Med., University of Georgia, Athens, GA, NEPFOS is currently being evaluated as a pest^ cide for the red imported fire ant. ' Previou* studies from this laboratory* showed that a* early effect of NEPFOS and PFOS on rabbit renal proximal tubules was- a concentration-dependent (5-200 uM) increase in ouabain-insensitive res piration (RESP). The goal of this study was to determine whether the increased RESP resulted -*g from uncoupling of oxidative phosphorylation (OX ---1 PHOS). NEPFOS (5-100 uM) and PFOS (0.5-50 uM) increased state 4 RESP of RCM respiring on pyni* vate/malate or succinate in the absence of * phosphate acceptor or in the presence of oligo* mycin, an inhibitor of FOFl-ATPase. The effect of NEPFOS (200 uM), PFOS (100 uM), and the known protonophore FCCP (luM), on proton movement by RCM was examined. Immediately on addition, PFOS and,FCCP, but not NEPFOS, dissipated the proton 1 gradient. These results show that PFOS acts as 1 a protonophore and uncouples OX PHOS by this mechanism. The lack of proton movement by >NEPFOS suggests that NEPFOS may need to be metabolized toPFOS to produce cytotoxicity and uncoupling of OX PHOS. (Supported by VMES, tlniv. Georgia). nesm cT fo w l T itn c m fit Strm tTiuG. BESTCOPYAVMUILE 001007