Inhibition of cell-cell communication by commercial chlorinated paraffins in rat liver epithelial IAR 20 cells.
The effects of six commercial chlorinated paraffins of different carbon chains length and chlorine content (Cereclor 50LV [C50LV], Hüls 60 [H60], Cereclor S45 [CS45], Cereclor S52 [CS52], Cereclor 42 [C42] and Cereclor 48 [C48] on cell communication have been investigated in the scrape-loading/dye-transfer assay in IAR 20 rat liver epithelial cells, as well as the effects of these compounds on connexin 43 (cx 43), the main gap junction protein in this cell line. The results clearly demonstrated that at non-cytotoxic concentrations C50LV, H60, CS45 and CS52 completely inhibited the cell communication within 1 hr. The short carbon chain length chlorinated paraffins (C50LV and H60) were inhibiting the cell communication at lower concentration than the intermediate carbon chain length chlorinated paraffins (CS45 and CS52). Almost complete inhibition of the cell communication was maintained for at least 24 hrs of H60 exposure. Immunoblots of IAR 20 cell extracts after H60-exposure showed a decreased phosphorylation of cx 43 after 1, 4 and 24 hrs of treatment. The phosphorylation pattern of cx 43 prepared from H60- or CS52-exposed cells was different from that prepared from 12-O-tetradecanoylphobol-13-acetate (TPA)-exposed cells after 1 hr treatment. The results show that the short and intermediate, but not the long carbon chain length chlorinated paraffins, are potent inhibitors of gap junction intercellular communication. Thus, our findings suggest that these compounds may act as tumour promoters.
Kato
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Y
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Kenne
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K
D000818:Animals; D015153:Blotting, Western; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D018031:Connexin 43 / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D017629:Gap Junctions / Q000187:drug effects; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D010766:Phosphorylation; D051381:Rats; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D018031:Connexin 43; D006843:Hydrocarbons, Chlorinated; D013755:Tetradecanoylphorbol Acetate