IRON CHELATORS INDUCE APOPTOSIS IN PROLIFERATING CELLS

The iron chelators 1,2-dimethyl-3-hydroxypyrid-4-one (L(1)) and desferrioxamine (DFO) were found to induce apoptosis of proliferating activated T-lymphocytes and of the promyelocytic cell line HL60, but not of resting peripheral blood lymphocytes or granulocytes. The induction of apoptosis was quantified by propidium iodide staining of apoptotic/dead cells and now cytometry. In activated T-lymphocytes incubated with the chelators at equivalent iron-binding concentrations (300 mu M L(1) or 100 mu M DFO) for 24h, L(1) caused a 54% increase in cell death and DFO a 57% increase. In Ht60 cells L(1) caused a 50% increase in cell death and DFO a 40% increase. DNA cytofluorometry of HL60 cells treated with either chelator showed an increase in the percentage of cells with hypodiploid DNA content. Presaturation of the chelators with ferric chloride abrogated these effects. L(1) and DFO did not induce apoptosis in resting peripheral blood lymphocytes or granulocytes, even after 48 h of incubation.