Induction of DNA fragmentation by nicotine in human myelogenous leukemic cell lines.

The effect of nicotine, a component of tobacco, on the cytokine production and cell growth of various cultured cells was investigated. Nicotine did not stimulate, but rather inhibited the tumor necrosis factor production by human peripheral blood mononuclear cells at higher doses. Cytotoxic concentrations of nicotine did not induce the monocytic and granulocytic differentiation of human myelogenous leukemic cell lines (HL-60, ML-1). Nicotine induced internucleosomal DNA cleavage in these leukemic cell lines but not in human peripheral blood lymphocytes and polymorphonuclear cells. The fragmentation-inducing activity of nicotine was not prevented by simultaneous addition of ascorbic acid. Flow cytometry showed a slight increase in the number of G2 + M phase cells, 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 calcium concentration above a certain threshold level.