THE EFFECT OF 12-O-TETRADECANOYLPHORBOL-13-ACETATE (TPA) ON PHOSPHOLIPID-METABOLISM OF HUMAN EPIDERMAL-KERATINOCYTES IN CULTURE

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated the release of [3H]choline from prelabelled membrane phospholipids of cultured keratinocytes obtained from normal human skin. In contrast, TPA in the concentration range of 10-12 to 10-6 g/ml failed to iduce deacylation of [3H]arachidonic acid or stimulate [3H]prostaglandin production in prelabelled keratinocytes. In addition, TPA did not induce [3H]choline incorporation into the membrane phospholipids of these cells. The previously reported inability of TPA to stimulate a proliferative response in these cell cultures may be related to the resistance of these cells to TPA-induced alterations of arachidonate metabolism.