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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
Hu, W., P. D. Jones, B. L. Upham, J. E. Trosko, C. S. LAU, AND J. P. GIESY. 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. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 68(2):429-436, (2002).
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, 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 reversibly. Perfluorobutane sulfonic acid (PFBS) showed no significant effects on GJIC within the concentration range tested. A structure activity relationship was established among all four 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 two 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.