INDUCTION OF DNA FRAGMENTATION BY NICOTINE IN HUMAN MYELOGENOUS LEUKEMIC-CELL LINES

The effect of nicotine, a component of tobacco, on the cytokine produc tion and cell growth of various cultured cells was investigated. Nicot ine did not stimulate, but rather inhibited the tumor necrosis factor production by human peripheral blood mononulcear cells at higher doses . Cytotoxic concentrations of nicotine did nor induce the monocytic an d granulocytic differentiation of human myelogenous leukemic cell line s (HL-60, ML-I). Nicotine induced internucleosomal DNA cleavage in the se leukemic cell lines but not in human peripheral blood lymphocytes a nd polymorphonuclear cells. The fragmentation-inducing activity of nic otine was not prevented by simultaneous addition of ascorbic acid. Flo w cytometry showed a slight increase in the number of G2 + M phase cel ls, before the appearance of the apoptosis peak. Nicotine transiently increased the intracellular calcium concentration to higher levels in leukemic cells than in normal leukocytes. These data suggest that the induction of DNA fragmentation requires elevation of intracellular cal cium concentration above a certain threshold level.