PHORBOL ESTER-INDUCED EFFECTS ON CELL-CYCLE PROGRESSION AND TERMINAL DEOXYNUCLEOTIDYLTRANSFERASE (TDT) ACTIVITY IN KM-3 PRE-B-CELL LINE

Phorbol myristic acetate (PMA) is a tumor-promoting agent that has bee n shown to induce differentiation of human leukemia cells and of norma l lymphoid cells. We have investigated the ability of PMA to induce in hibition of cell growth of the human KM-3 pre-B leukemic cell line by multiparametric analysis. Our results show that PMA treatment induces cell differentiation with the disappearance of terminal deoxynucleotid yltransferase and a decrease of cell growth. as evaluated by [H-3]thym idine uptake. Flow cytometric analysis of BrdU incorporation shows tha t PMA is able to induce a modification of the cell cycle with a sharp decrease of the percentage of S-phase cells, which is more evident aft er 24 h of treatment. Comparison between the cell growth kinetics and TdT synthesis and activity shows that differentiated cells are still a ble to proliferate to a certain extent and that the TdT disappearance and the initial decrease of cell proliferation are two independent eff ects of PMA.