Inhibition of gap junctional intercellular communication by perfluorinated compounds in rat liver and dolphin kidney epithelial cell lines in vitro and sprague-dawley rats in vivo
Inhibition of gap junctional intercellular communication by perfluorinated compounds in rat liver and dolphin kidney epithelial cell lines in vitro and sprague-dawley rats in vivo
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DOI：
10.1093/toxsci/68.2.429
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发表时间：
2002-08-01
影响因子：
3.8
通讯作者：
Giesy, JP
中科院分区：
文献类型：
--
作者：
Hu, WY;Jones, PD;Giesy, JP
细胞间隙连接通讯（GJIC）是细胞间信号转导的主要途径，对细胞的正常生长和功能具有重要意义。最近的研究表明，一些全氟有机化合物，特别是全氟辛烷磺酸在环境中的全球分布。由于其他全氟烷烃已被证明会抑制GJIC，因此使用大鼠肝上皮细胞系（WB-F344）和海豚肾上皮细胞系（CDK）研究了全氟辛烷磺酸和相关磺化含氟化合物对GJIC的影响。研究了经口接触全氟辛烷磺酸3天或3周的Sprague-Dawley大鼠体内对GJIC的影响。采用刮片加载染料技术测量对GJIC的影响。研究发现，全氟辛烷磺酸、全氟辛烷磺酰胺和全氟己烷磺酸以剂量依赖方式抑制GJIC，而且这种抑制作用发生迅速且可逆。全氟丁烷磺酸（PFBS）在测试的浓度范围内对GJIC没有显着影响。所有4个测试化合物之间建立了构效关系，表明抑制效果是由氟化尾的长度而不是由官能团的性质决定的。2种细胞系的研究结果和体内暴露结果相当，表明所选全氟化合物对GJIC的抑制作用既不具有种属特异性，也不具有组织特异性，并且可以在体外和体内发生。
Gap junctional intercellular communication (GJIC) is the major pathway of intercellular signal transduction, and is thus important for normal cell growth and function. Recent studies have revealed a global distribution of some perfluorinated organic compounds, especially perfluorooctane sulfonic acid (PFOS) in the environment. Because other perfluoroalkanes had been shown to inhibit GJIC, the effects of PFOS and related sulfonated fluorochemicals on GJIC were studied using a rat liver epithelial cell line (WB-F344) and a dolphin kidney epithelial cell line (CDK). In vivo effects on GJIC were studied in Sprague-Dawley rats orally exposed to PFOS for 3 days or 3 weeks. Effects on GJIC were measured using the scrape loading dye technique. PFOS, perfluorooctane sulfonamide (PFOSA), and perfluorohexane sulfonic acid (PFHA) were found to inhibit GJIC in a dose-dependent fashion, and this inhibition occurred rapidly and was reversible. Perfluorobutane sulfonic acid (PFBS) showed no significant effects on GJIC within the concentration range tested. A structure activity relationship was established among all 4 tested compounds, indicating that the inhibitory effect was determined by the length of fluorinated tail and not by the nature of the functional group. The results of the studies of the 2 cell lines and the in vivo exposure were comparable, suggesting that the inhibitory effects of the selected perfluorinated compounds on GJIC were neither species- nor tissue-specific and can occur both in vitro and in vivo.