Accession Number : ADA282452

Title :   The Role of Chemical Inhibition of Gap Junctional Intercellular Communication in Toxicology.

Descriptive Note : Annual technical rept. 14 May 93-15 May 94,

Corporate Author : MICHIGAN STATE UNIV EAST LANSING DEPT OF PEDIATRICS/HUMAN DEVELOPMENT

Personal Author(s) : Trosko, James E.

Report Date : 14 JUN 1994

Pagination or Media Count : 206

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.

Descriptors :   *GENES, *NEOPLASMS, *CELL DIVISION, *TOXICITY, CHEMICALS, CONTROL, DDT, ESTERS, INHIBITION, PHOSPHORYLATION, RISK, PROTEIN METABOLISM, TERATOGENIC COMPOUNDS, MOLECULAR BIOLOGY, PROTEINS(DERIVED), DEOXYRIBONUCLEIC ACIDS.

Subject Categories : Biochemistry
      Toxicology

Distribution Statement : APPROVED FOR PUBLIC RELEASE