Levitt D, Liss A
J Toxicol Environ Health. 1987;20(3):303-16. doi: 10.1080/15287398709530983.
We have evaluated the effect of the perfluorinated fatty acids pentadecafluoro-n-octanoic acid (PFOA) and nonadecafluoro-n-decanoic acid (NDFDA) on the ability of a human B-lymphoblastoid cell line to bind the lipid-binding, membrane-impermeant, fluorescent dye merocyanine 540 (MC540). Subtoxic concentrations of perfluorinated fatty acids (0.9 mM PFOA; 0.5 mM NDFDA) greatly diminish binding of MC540 by normal plasma membranes, as determined by fluorescence flow cytometry. When perfluorinated fatty acids are added to cells at toxic or lethal concentrations (1.2 mM PFOA; 0.75 mM NDFDA), MC540 binding increases dramatically, with entrance of dye to internal membrane domains. Neither perfluorinated fatty acid molecule reduces the ability of surface immunoglobulin to migrate laterally and cap on cells. Our data suggest that perfluorinated fatty acids either interact directly with lipid binding sites for MC540, and thereby inhibit dye intercalation, or alter membrane lipid architecture and lipid packing to diminish MC540 binding. Both possibilities support a direct, physical, membrane-altering mechanism for perfluorinated fatty acid toxicity on mammalian cells.
我们评估了全氟脂肪酸十五氟正辛酸（PFOA）和十九氟正癸酸（NDFDA）对人B淋巴母细胞系结合脂结合、膜不透性荧光染料部花青540（MC540）能力的影响。通过荧光流式细胞术测定，全氟脂肪酸的亚毒性浓度（0.9 mM PFOA；0.5 mM NDFDA）极大地降低了正常质膜对MC540的结合。当以毒性或致死浓度（1.2 mM PFOA；0.75 mM NDFDA）向细胞中添加全氟脂肪酸时，MC540结合显著增加，染料进入内膜结构域。两种全氟脂肪酸分子均不降低表面免疫球蛋白在细胞上横向迁移和形成帽状结构的能力。我们的数据表明，全氟脂肪酸要么直接与MC540的脂质结合位点相互作用，从而抑制染料插入，要么改变膜脂质结构和脂质堆积以减少MC540结合。这两种可能性都支持全氟脂肪酸对哺乳动物细胞毒性的直接物理膜改变机制。
