To define the role of gap-junctional communication in tumor promotion, nonpromotable, promotable, and tumorigenic transformed epidermis-derived cells of line JB6 cells were subjected to the tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA). Cell- cell communication was measured either by the radioisotope transfer technique or by microinjection of fluorescent dye. The capability of TPA-treated cells to escape from the controlling influence of non-promotable neighboring cells was monitored by the evaluation of colony formation on irradiated feeder cell layers. Our results give evidence for a blocked cell-cell communication during the initial exposure to TPA. However, the number of colonies evolving from promotable cell clones in the presence of TPA does not correlate to the magnitude of the initial interruption of intercellular communication. Thus, it has to be concluded that, in the model system used, the suppressive effect of TPA on intercellular communication may not primarily be related to the promoting effect on cell growth. Also, reduced intercellular communication is not a decisive factor in maintaining malignancy. Interruption of gap-junctional intercellular communication was used as indicator in a short-term test mode to uncover tumor-promoting properties in chemical agents, such as Ni-(II)-salts.
