Inhibition of intercellular communication between mouse hepatocytes by tumor promoters.
Tumor promoters can inhibit gap junction-mediated intercellular communication in cultured cells. Since intercellular communication is thought to be important in normal cellular growth control, inhibition of intercellular communication by tumor promoters may be an important mechanism by which preneoplastic cells escape normal growth regulation and progress towards neoplasia. We have evaluated the effects of tumor promoters on intercellular communication between B6C3F1 mouse hepatocytes in primary culture. "Donor" hepatocytes were labeled with 4 microCi[5-3H]uridine/ml for 4 hr. Nonlabeled "recipient" hepatocytes were then plated onto and cocultured with the labeled donors. Hepatocyte cultures were then treated with either the tumor promoters or the solvent vehicle. After 2-24 hr, the cells were fixed and processed for autoradiography. Intercellular communication between donor and recipient hepatocytes was detected as an increase in autoradiographic grains over recipient cells in contact with donor cells, indicating the passage of labeled nucleotides from donor to recipient hepatocytes. Autoradiographic grains were not observed over recipient hepatocytes not in contact with donor cells thus indicating negligible transfer of labeled nucleotide through the medium. Intercellular communication in untreated and solvent vehicle treated hepatocytes was detected in approximately 80% of the donor-contacting recipients after 8-12 hr culture. Phenobarbital, DDT (1,1-bis(4-chlorophenyl)-2,2,2-trichloroethane), Aroclor 1254, lindane (1,2,3,4,5,6-hexachlorocyclohexane, gamma-isomer), and TPA (12-O-tetradecanoyl phorbol-13-acetate), at noncytotoxic concentrations, significantly decreased hepatocyte intercellular communication in a dose-dependent manner.
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D020111:Chlorodiphenyl (54% Chlorine); D003634:DDT / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D001556:Hexachlorocyclohexane / Q000494:pharmacology; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D010634:Phenobarbital / Q000494:pharmacology; D012313:RNA / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014529:Uridine / Q000378:metabolism
D001140:Aroclors; D002273:Carcinogens; D020111:Chlorodiphenyl (54% Chlorine); D001556:Hexachlorocyclohexane; D012313:RNA; D003634:DDT; D013755:Tetradecanoylphorbol Acetate; D014529:Uridine; D004121:Dimethyl Sulfoxide; D010634:Phenobarbital