Transport of 14C-deferiprone in normal, thalassaemic and sickle red blood cells.

The transport of deferiprone (L1) in normal (N), sickle (S) and thalassaemic (T) red blood cells (RBC) was determined by incubation with 14C-L1 at 37 degrees C. Following incubation with 0.5 mM 14C-L1 for 4 h, the intracellular concentration of L1 in T RBC was 3 times higher than was found extracellularly. In contrast, no concentration gradient across N and S RBC membranes was detected. Efflux studies showed that T RBC released only 17 +/- 2% of 14C-L1 into the extracellular space. We hypothesize that L1 accumulation in T RBC results from their high content of chelatable iron and formation of large, hydrophilic L1-Fe(III) complexes trapped within the cytosol.

Iron chelators induce apoptosis in proliferating cells.

The iron chelators 1,2-dimethyl-3-hydroxypyrid-4-one (L1) 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 flow cytometry. In activated T-lymphocytes incubated with the chelators at equivalent iron-binding concentrations (300 microM L1 or 100 microM DFO) for 24 h, L1 caused a 54% increase in cell death and DFO a 57% increase. In HL60 cells L1 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. L1 and DFO did not induce apoptosis in resting peripheral blood lymphocytes or granulocytes, even after 48 h of incubation.