The Role of Chemical Inhibition of Gap-Junctional Intercellular Communication in Toxicology
Final rept. 15 Feb 1986-28 Feb 1989
MICHIGAN STATE UNIV EAST LANSING DEPT OF PEDIATRICS/HUMAN DEVELOPMENT
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The overall goal of this grant has been to study the mechanisms by which non-genotoxic chemicals act. Specifically, the working hypothesis has been that chemical modulation of gap junctions could lead to many toxic endpoints, such as teratogenesis, tumor promotion, immune-reproductive- and neuro- toxicities. To test this hypothesis, we set up several aims a to develop new methods to measures to measure gap junction function Fluorescence Recovery After Photo-bleaching and scrape-loadingdye transfer b to test if several known model non-genotoxic chemicals inhibit intercellular communication in several cell types and c to study the biochemical mechanisms by which various chemicals inhibit intercellular communication. Results of this 3 year study have produced a three new validated in vitro methods to measure gap junction b produced overwhelming evidence that known non-genotoxic teratogens, tumor promoters, neuro-, and reproductive-toxicants can inhibit gap junction function c evidence suggesting several biochemical mechanisms by which these chemicals act and d helped develop a new theoretical framework for a biologically-based risk assessment model system.