Interruption of Cell-Cell Communication in Chinese Hamster V79 Cells by Various Alkyl Glycol Ethers: Implications for Teratogenicity

• Published in: Environmental health perspectives Vol. 57; pp. 119 - 123
• Main Authors: Loch-Caruso, Rita, Trosko, James E., Corcos, Isabel A.
• Format: Journal Article
• Language: English
• Published: United States National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare 01.08.1984
• Subjects: Animals; Biotransformation; Cell communication; Cell Communication - drug effects; Cell culture techniques; Cell lines; Cell Survival - drug effects; Cells, Cultured; Cellular metabolism; Cricetinae; Cricetulus; Cultured cells; Cytotoxicity; Embryos; Ethers; Ethylene Glycols - toxicity; Gap junctions; Glycols; Symposium on Toxic Effects of Glycol Ethers, September 19-21, 1983, Cincinnati, Ohio; Teratogens
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.8457119

Intercellular communication most likely plays a significant coordinating role in morphogenesis. Blockage of a specific type of intercellular communication, that mediated by gap junctions, has been proposed as a mechanism of action of some teratogens. Several glycol ethers have recently been shown to be teratogenic in laboratory animals. Because these compounds are negative in genotoxic assays, it is suggested that they may act by nongenetic, perhaps membrane-mediated mechanisms. In the present study several structurally related alkyl glycol ethers were examined for their ability to block junction-mediated intercellular communication. Interruption of intercellular communication was measured in vitro by an assay that depends on the transfer of metabolites via gap junctions, i.e., metabolic cooperation. All compounds tested-ethylene glycol (EG), ethylene glycol monomethyl ether (EGME), ethylene glycol monoethyl ether (EGEE), ethylene glycol monopropyl ether (EGPE), and ethylene glycol monobutyl ether (EGBE)-were able to block metabolic cooperation in vitro. The potencies of the compounds were inversely related to the length of the aliphatic chain, the dose required for maximum blockage increasing as the aliphatic chain shortened. Some differences in the maximum amount of blockage were detected, but these were not consistent and hence were not considered significant. Cytotoxicity, as measured by cell survival, was also related to the structure of the compound, generally increasing with increased length of the aliphatic chain. There were structurally related differences in the concentration ranges over which the compounds were effective. The noncytotoxic ranges over which communication was blocked became reduced as the length of the aliphatic chain increased. EG was effective over the broadest range, followed by EGME. The remaining compounds had very narrow effective ranges relative to EG and EGME. Because they are effective over such broad noncytotoxic ranges, blockage of intercellular communication may be most significant as a teratogenic mechanism for EG and EGME. Although the other compounds in the series also blocked communication, they were more cytotoxic and they interrupted communication in a relatively narrow window of concentrations. Consequently, interrupted intercellular communication may be mixed with cytotoxicity in the embryo and the mother, and thus be less specific as a mechanism of teratogenesis for EGEE, EGPE and EGBE.