Modulation of mitogenicity and ATPase activities in human lymphocytes in the presence of 12-O-tetradecanoylphorbol 13-acetate and phytohemagglutinin

In view of the poor evidence concerning the effects of 12-O-tetradecanoylphorbol 13-acetate (TPA) and phytohemagglutinin (PHA) on ATPase activities, we decided to study the effects of TPA and PHA on ATPases in human lymphocytes. In parallel, the mitogenic effects of TPA and PHA were followed. The optimal doses for mitogenicity as well as ATPase activities were 5 μg/ml for PHA and 20 ng/ml for TPA. PHA 5 μg/ml was significantly more mitogenic than TPA 20 ng/ml. TPA inhibited the mitogenicity of PHA. Catalase increased the mitogenicity of TPA, while it had no effect on PHA and on PHA + TPA. There was no correlation between the mitogenic effects and ATPases activities. The effect of TPA on ATPases was much more pronounced than the effect of PHA. TPA had a dramatic effect especially on Mg and Ca ATPases (5-fold increase in comparison with control) and a small but significant influence on Na/K ATPase (2-fold). PHA had a small but significant effect on the three ATPases. PHA inhibited the ATPase activities induced by TPA. Catalase had no effect on TPA induced ATPases, in contrast to its effect on mitogenesis. The elucidation of the exact mechanisms responsible for ATPase activation and mitogenicity by TPA may be important for the better understanding of carcinogenesis in general and the promotion stage of carcinogenesis in particular.