Inhibition of intercellular communication between normal human embryonal palatal mesenchyme cells by teratogenic glycol ethers.
Cell-cell communication, possibly through gap junctions, is a fundamental event for the differentiation of embryonal tissues. Chemical substances which can interfere with this process may be able to disrupt embryogenesis. We have examined the response of a normal diploid human embryonal palatal mesenchymal (HEPM) cell line to glycol ethers. These cells have gap junctions whose function in cell-cell communication was inhibited by a model teratogen. Potential HEPM donor cells (2000 to 4000) were pulse labeled with 3H-uridine (10 microCi/mL; 3 hr) and then cocultured for 3 hr with 200,000 to 400,000 potential recipient cells in the absence or presence of 2-methoxyethanol (ME; 0.13-0.30 M) or 2-isopropoxyethanol (IPE; 0.05-0.1 M). Computer-assisted quantitative autoradiography was applied to assess the effects on metabolic cooperation. Although this phenomenon was inhibited by ME, the effect was probably not attributable to interference with gap junction-mediated transfer of labeled nucleotides but rather to the lack of formation of gap junctions resulting from cytotoxicity and poor physical contact between cells. The inhibition obtained with IPE was apparently not due to adverse effects on HEPM cells as judged by light microscopy and cell counts of recipients surrounding a given donor. The results suggest that HEPM cells are suitable to study disruption of cell-cell communication as a mechanism responsible for teratogenesis and offer the unique possibility to apply human embryonal cells. However, care has to be taken to assess potential cytotoxicity of xenobiotics, and further refinement of the criteria to detect adverse effects is required.
D001345:Autoradiography; D001711:Biotransformation; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005026:Ethylene Glycols / Q000633:toxicity*; D005260:Female; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D010159:Palate / Q000166:cytology; D011247:Pregnancy; D013194:Staining and Labeling; D013723:Teratogens; D014529:Uridine / Q000378:metabolism
D005026:Ethylene Glycols; D013723:Teratogens; C008204:isopropylethanediol; C005219:methyl cellosolve; D014529:Uridine