Failure of the tumor promoter 12-o-tetradecanoylphorbol-13-acetate (tpa) to inhibit cell-cell coupling in newborn mouse epidermal cells and chinese hamster v79 cells under non-standard culture conditions

The function of the skin tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) during two-stage carcinogenesis in mice remains obscure because of TPA's numerous phenotypic effects. In vitro studies under established conditions have generated substantial interest in TPA's ability to inhibit, although transiently in some cases, direct cell-cell coupling in several permanent cell lines, by analogy allowing latent 'initiated cells' to escape homeostatic controls in vivo. Using different culture conditions designed to improve the growth of newborn mouse epidermal cells, we examined dye coupling in these cells, and metabolic co-operation in V79 cells, finding no effect of TPA on coupling. It appears that this effect of TPA is overly sensitive to in vitro conditions. Since a corresponding physiological effect has not yet been demonstrated in vivo, future studies should be directed to establish that coupling inhibition by TPA actually does occur and plays some role during tumor promotion in vivo, and is not merely a characteristic of certain culture systems.