Toxicological Sciences 68, 429-436 (2002)
Copyright © 2002 by the Society of Toxicology
MOLECULAR AND GENETIC TOXICOLOGY |
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
* Aquatic Toxicology Laboratory, Department of Zoology, National Food Safety and Toxicology Center and Institute of Environmental Toxicology, Michigan State University, East Lansing, Michigan 48824;
Department of Pediatrics and Human Development and National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan 48824; and
Reproductive Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
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.
Key Words: GJIC; PFOS; perfluorinated chemicals; rodents; QSAR.
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