title: Inhibition of gap junctional-mediated intercellular communication in vitro by aldrin, dieldrin, and toxaphene: a possible cellular mechanism for their tumor-promoting and neurotoxic effects.
abstract: Several mechanisms have been postulated to be responsible for the pleiotropic effects of toxic chemicals. Although the cytotoxicity and mutagenicity of chemicals are well studied and relatively easily detected, the noncytotoxic and nonmutagenic (i.e., epigenetic) mechanisms of chemical toxicity are less well understood. An in vitro assay, using cocultures of Chinese hamster cells to measure metabolic cooperation between V79 6-thioguanine-sensitive (6TGs) and resistant (6TGr) cells, has been developed to detect noncytotoxic and nonmutagenic chemicals that inhibit, quantitatively, gap junctional communication. The insecticides aldrin, dieldrin, and toxaphene, known to have pleiotropic toxic effects in animals, were shown to inhibit gap junctional communication. Interpretation of results suggests that chemical inhibition of gap junctional communication could be a possible mechanism to explain their tumor-promoting and neurotoxic effects.
authors.affiliation: Department of Pediatrics/Human Development, Michigan State University, East Lansing 48824.
authors.forename: J E
authors.initials: JE
authors.lastname: Trosko
authors.forename: C
authors.initials: C
authors.lastname: Jone
authors.forename: C C
authors.initials: CC
authors.lastname: Chang
mesh_terms: D000452:Aldrin / Q000494:pharmacology*; D000818:Animals; D002273:Carcinogens; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004026:Dieldrin / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007306:Insecticides / Q000494:pharmacology*; D007365:Intercellular Junctions / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014112:Toxaphene / Q000494:pharmacology*
chemical_list: D002273:Carcinogens; D007306:Insecticides; D009498:Neurotoxins; D014112:Toxaphene; D004026:Dieldrin; D013755:Tetradecanoylphorbol Acetate; D000452:Aldrin