Subcellular distribution and protein binding of perfluorooctanoic acid in rat liver and kidney.

Perfluorooctanoic acid (PFOA) is an organic fluorochemical, and its elimination in rats is markedly sex-dependent. Liver and kidney are two primary tissues of distribution of PFOA in rats. In this study, the subcellular distribution of PFOA in male and female rat liver and kidney was examined. The results demonstrated that PFOA content in the liver cytosol of the female rat was significantly higher (49 +/- 6% of total radioactive residues, TRR) than in the male liver (26 +/- 5% TRR), whereas PFOA distribution in the heavier subcellular fractions, especially the nuclei and cell debris fraction, was marginally higher in male rat liver. In rat kidney, more than 70% of PFOA was distributed in the cytosolic fraction, with no significant difference between sexes. The degree of protein binding of PFOA in rat liver and kidney cytosol was analyzed by two different chromatographic methods. The percentage of protein-bound PFOA in the liver cytosol was found to be approximately 55% in both male and female rats. In contrast, significantly more PFOA was bound to cytosolic proteins in the kidney of male rats (42 +/- 6% TRR) than in females (17 +/- 5% TRR). Ligand blotting analysis revealed that multiple proteins from the liver cytosol, nuclei, and mitochondria fractions were capable of specific binding to PFOA.