Regulation of gap-junctional intercellular communication in transformation-sensitive and transformation-resistant...

BALB/c 3T3 A31-1-13 cells are highly susceptible to chemical-induced cell transformation and their gap-junctional intercellular communication (GJIC) is decreased when these cells become confluent. On the other hand, A31-1-1 cells do not show such a change in GJIC and are more resistant to chemical induction of transformation. In order to see which phenotypes are dominant, cells of these two types were hybridized and the hybrids were analyzed for their phenotypes for GJIC and induction of cell transformation. These two cell lines were tagged with neor gene or hygromycin-resistance gene respectively, and their hybrids were selected in medium containing G418 and hygromycin. Six independently isolated clones were characterized and all showed a loss of intercellular communication at confluence, suggesting that the phenotype of transformation-sensitive cell line A31-1-13 was dominant. However, when these hybrid cells were exposed to 3-methylcholanthrene, no transformed foci were produced, suggesting that the transformation-resistant phenotype is dominant. These results suggest that the regulation of GJIC and the susceptibility to chemical induction of transformation are genetically separate traits, and indirectly suggest that the loss of GJIC alone cannot explain the high susceptibility of A31-1-13 cells to induction of transformation.