Han Xing, Kemper Raymond A, Jepson Gary W
DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, Delaware 19714, USA.
Drug Chem Toxicol. 2005;28(2):197-209. doi: 10.1081/dct-52547.
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.
全氟辛酸（PFOA）是一种有机氟化合物，其在大鼠体内的消除具有明显的性别依赖性。肝脏和肾脏是PFOA在大鼠体内的两个主要分布组织。在本研究中，检测了PFOA在雄性和雌性大鼠肝脏及肾脏中的亚细胞分布。结果表明，雌性大鼠肝脏胞质溶胶中的PFOA含量（占总放射性残留量的49±6%）显著高于雄性大鼠肝脏（占总放射性残留量的26±5%），而在较重的亚细胞组分中，尤其是细胞核和细胞碎片组分中，PFOA在雄性大鼠肝脏中的分布略高。在大鼠肾脏中，超过70%的PFOA分布在胞质溶胶组分中，两性之间无显著差异。采用两种不同的色谱方法分析了PFOA在大鼠肝脏和肾脏胞质溶胶中的蛋白结合程度。发现雄性和雌性大鼠肝脏胞质溶胶中与蛋白结合的PFOA百分比均约为55%。相比之下，雄性大鼠肾脏中与胞质溶胶蛋白结合的PFOA（占总放射性残留量的42±6%）显著多于雌性大鼠（占总放射性残留量的17±5%）。配体印迹分析表明，来自肝脏胞质溶胶、细胞核和线粒体组分的多种蛋白质能够与PFOA特异性结合。
