Direct intercellular communication between adjoining cells can occur among cells in vitro and in vivo, most likely through specialized channels called gap junctions. It has been suggested that gap junctional communication plays an important role in embryonic development, germ cell maturation and parturition. Our proposed research will investigate inhibition of junctional communication as a possible mechanism of adverse reproductive outcome, and will test the validity of several short-term assays for the detection of reproductive toxins that may act by this mechanism. The first part of our research program will entail testing known and potential reproductive toxins for their ability to interrupt junctional communication using rapid, in vitro techniques. We will employ several different cell lines in an attempt to maximize the reliability of the in vitro systems as predictors for the human, in vivo situation. These cell lines will include Chinese hamster V79, human teratocarcinoma, human uterine and rat hepatocyte lines. The second focus of our research will be to validate inhibition of junctional communication as a mechanism of abnormal morphogenesis using hydra reaggregation as an in vivo developmental system. By differentially labeling and later mixing and reaggregating two populations of hydra cells, we hope to demonstrate that compounds which interfere with hydra reaggregation also interrupt junctional communication in vivo. These results will be compared to the results from cell systems to determine the reliability of the cell systems in predicting developmental toxicity. Finally, we will investigate molecular mechanisms of control of gap junction function. We will focus our efforts on protein phosphorylation, since this has been associated with growth factors, receptor function and junctional communication.
| Zidell, R H; Loch-Caruso, R (1990) A simple dye-coupling assay for evaluating gap junctional communication: the importance of transcription and translation on the establishment of dye-coupling. Cell Biol Int Rep 14:613-28 |
| Loch-Caruso, R; Caldwell, V; Cimini, M et al. (1990) Comparison of assays for gap junctional communication using human embryocarcinoma cells exposed to dieldrin. Fundam Appl Toxicol 15:63-74 |
