EFFECT OF TUMOR-PROMOTING AND ANTI-PROMOTING CHEMICALS ON THE VIABILITY AND JUNCTIONAL COUPLING OF HUMAN HELA-CELLS TRANSFECTED WITH DNAS CODING FOR VARIOUS MURINE CONNEXIN PROTEINS

Gap-junctional intercellular communication is thought to be essential for maintaining cellular homeostasis and growth control. Its perturbat ion entails toxicological implications and it has been correlated with the in vivo tumor-promoting potential of chemicals. Little is known a bout the mechanism(s) responsible for the tumor promoters interference with the cellular coupling. Moreover, nongenotoxic carcinogens, as we ll as connexins (gap-junctional protein subunits), are known to be org an-/tissue-specific; this implies that the effect of different agents should be evaluated on their specific target, that is, connexin. To in vestigate the role of different connexins in regulating gap-junctional gating and to compare the properties of homotypic junctional channels , we evaluated the effects of tissue-specific tumor promoters and anti -promoters on the viability and intercellular coupling (dye-transfer) of HeLa cells stably transfected with cDNAs coding for connexin(cx)43, cx40, cx26 and cx32. The results demonstrate that the transfectants p ossess individual junctional permeabilities, differentially affected b y the chemicals; they also show different sensitivities to the cytotox ic effect of the compounds. These findings confirm that connexin diver sity may be responsible for the different gating properties of gap-jun ctional channels, being also suggestive for their separate functions a nd independent regulatory mechanisms.