The Role of Chemical Inhibition of Gap Junctional Intercellular Communication in Toxicology.
Annual technical rept. 14 May 93-15 May 94,
MICHIGAN STATE UNIV EAST LANSING DEPT OF PEDIATRICS/HUMAN DEVELOPMENT
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Gap Junctional Intercellular Communication GJIC is the biological process which regulates homostatic control of cell proliferation, differentiation and adaptive functions of differentiated cells. Disruption of GJIC by toxic chemicals, either at the level of gene expression or protein function, has been correlated with teratogenesis, tumor promotion, reproductive and neurotoxicities. The mechanisms by which various epigenetic toxicants or oncogenes inhibit GJIC have been studied in this project. Modulation of phosphorylation of one gap junction protein cx43 by two different tumor promoters phorbol esters, DDT has been shown to be different, yet the end result inhibition of GJIC is the common end point. Preliminary evidence has linked the toxic-chemical modification of the gap junction protein phosphorylation paths with altered trafficking of the protein within the cell. Further studies will extend these studies to build a solid mechanistic base for a biological risk assessment model for epigenetic or non-genotoxic chemicals.