title: 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.
abstract: 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.
authors.affiliation: Aquatic Toxicology Laboratory, Department of Zoology, National Food Safety and Toxicology Center and Institute of Environmental Toxicology, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Wenyue
authors.initials: W
authors.lastname: Hu
authors.forename: Paul D
authors.initials: PD
authors.lastname: Jones
authors.forename: Brad L
authors.initials: BL
authors.lastname: Upham
authors.forename: James E
authors.initials: JE
authors.lastname: Trosko
authors.forename: Christopher
authors.initials: C
authors.lastname: Lau
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
mesh_terms: D017738:Alkanesulfonic Acids / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects*; D005260:Female; D005466:Fluorocarbons / Q000737:chemistry / Q000633:toxicity*; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D007668:Kidney; D008099:Liver / Q000187:drug effects*; D008297:Male; D010473:Perciformes; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000633:toxicity
chemical_list: D017738:Alkanesulfonic Acids; D004785:Environmental Pollutants; D005466:Fluorocarbons; D013449:Sulfonamides; C063900:perfluorooctanesulfonamide; C076994:perfluorooctane sulfonic acid