The Role of Chemical Inhibition of Gap Junctional Intercellular Communication in Toxicology.
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 14, 1994
- Accession Number
- ADA282452
Entities
People
- James E. Trosko
Organizations
- Michigan State University