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.

Acute Enhancement of Synaptic Transmission and Chronic Inhibition of Synaptogenesis Induced by Perfluorooctane Sulfonate through Mediation of Voltage-Dependent Calcium Channel

“…The doses (1, 10, and 100 µM) of PFCs were administrated according to previous literature (7,14). Primary hippocampal neuron cultures and acute hippocampal slices from SpragueDawley rats were prepared as described previously (15,16).…”

“…Evidences showed that PFOS accumulates up to 1-10 mg/kg (approximately 2-20 µM) in some animal tissues (1) and 1.82 µM in serum of occupational workers (4). The potential toxicity of PFOS, such as hepatotoxicity, interference with mitochondrial bioenergetics, impeding intercellular communication through gap junctions, endocrine dysfunction, effects on development and reproduction, and carcinogenicity, has been documented (3,6,7). A previous study revealed that PFOS accumulates in rat brain after subchronic exposure (6).…”

Circumpolar Study of Perfluoroalkyl Contaminants in Polar Bears (Ursus maritimus)

“…The U. S. Environmental Protection Agency has expressed concern over effects of these types of compounds, due to their potential for accumulation and toxicity to humans and wildlife (3). Perfluorocarboxylic acids (PFCAs) are peroxisome proliferators (4) as well as tumor promoters (5) and may inhibit gap junction intercellular communication at environmentally relevant concentrations (5).…”

Biochemical effect evaluation of perfluorooctane sulfonic acid-contaminated wood mice (Apodemus sylvaticus).

“…Known in vivo effects of perfluorochemical exposure are an increase of the relative liver weight in the rat, mouse, and cynomolgus monkey and the induction of peroxisomal fatty acid β-oxidation and effects on several biochemical end points related to oxidative stress in the rat and mouse (Ikeda et al 1985(Ikeda et al , 1987Permadi et al 1992Permadi et al , 1993Sohlenius et al 1993). Other documented effects are the induction of hypolipemia in the rat, mouse, and cynomolgus monkey (Haughom and Spydevold 1992;Lau et al 2001;Seacat et al 2002) and the inhibition of gap junction intercellular communication (Hu et al 2002) and effects on carboxylesterase expression in the rat (Derbel et al 1996). Developmental and maternal effects in the rabbit, rat, and mouse (Lau et al 2001;York et al 2000) and promotion of carcinogenesis in the rat (Abdellatif et al 1990) have also been reported.…”