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INFLUENCE OF SODIUM ARSENITE ON GAP JUNCTION COMMUNICATION IN RAT LIVER EPITHELIAL CELLS
Citation:
GRINDSTAFF, R., S G. Benane, C F. Blackman, AND R. L. Turnage. INFLUENCE OF SODIUM ARSENITE ON GAP JUNCTION COMMUNICATION IN RAT LIVER EPITHELIAL CELLS. Presented at American Society for Cell Biology Annual Meeting, Washington, DC, 12/8-12/2001.
Description:
Influence of sodium arsenite on gap junction communication in rat-Iiver epitheiial cells.
Arsenic is known to cause certain types of cancers, hepatitis, cirrhosis and neurological disorders as well as cardiovascular and reproductive effects and skin lesions. The mechanism responsible for arsenic-induced carcinogenesis is not yet known. Evidence indicates arsenic disrupts signal transduction pathways that regulate cell proliferation and apoptosis. Gap junction communication (GJC), which is a component of intercellular signalling mechanisms, is studied here to investigate a possible non-genetic mode of action for arsenic-induced carcinogenesis. The gene responsible for GJC has tumor suppresser properties and the protein product appears to be a site of action for some non-genotoxic carcinogens. We used the scrape/load assay to observe the transfer of Lucifer Yellow fluorescent dye between Clone 9 rat-Iiver epithelial cells as a measure of GJC. We observed a sodium arsenite dose-dependent (0,20, 30, 40 & 50 x 10-6 M) and time-dependent (4, 7, 16 & 24 hours) inhibition of GJC in the absence of cell toxicity. Immuno-cytochemistry (ICC) showed reduced amounts of connexin 43 (Cx 43) in the plasma membrane after 24 hours of treatment. Pilot ICC data using the phospho -tyrosine antibody, py 20, showed a 24-hour treatment of Clone 9 cells with sodium arsenite caused an increase in the number of phosphorylation sites at low concentration (5 x 10~6 M) with a return to control values at higher arsenite levels. These results provide the motivation to continue this line of investigation to establish the mode of action by which GJC is altered by arsenical compounds
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This abstract does not reflect EPA policy.