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(T/EH038) Comparisons among perfluorinated compounds of effects on Gap Junctional Intercellular Communication. Hu, Wenyue1, Jones, Paul1, Upham, Brad2, Trosko, James2, Giesy, John1, 1 2 ABSTRACT- Gap Junctional Intercellular Communication (GJIC) is the major pathway of intercellular signal transduction and is thus very important for normal cell growth and function. Down regulation of GJIC has been linked to the carcinogenicity of a number of environmental contaminants. Recent studies have revealed a global distribution of perfluorinate compounds especially perfluorooctane sulfonic acid (PFOS) in the environment. Therefore, the effects of PFOS, perfluorooctanoic sulfonamide (PFOSA), perfluorohexane sulfonate (PFHS) and perfluorobutane sulfonate (PFBS) on GJIC were studied using a rat liver epithelial cell line (WB-F344) and a dolphin kidney epithelial cell line (CDK). Effects on GJIC were measured using the scrape loading dye technique. PFOS, PFOSA, PFHA were found to inhibit GJIC in a dose-dependent fashion, and this inhibition occurred rapidly and reversibly. PFBS showed no significant effects on GJIC within the concentration range tested. A structure activity relationship was established for compounds tested, and it was indicated that the inhibitory effect was determined by the length of the fluorinated carbon chain and was independent of the functional group. Since the results from two cell lines were comparable to each other, it was also suggested that the inhibitory effects of the tested sulfonated fluoro-compounds on GJIC were neither species- nor tissue- specific. Key words: perfluorinated compounds, cell-cell communication, non-genotoxic carcinogens |
