Desferrioxamine (10(-3) M) caused a fall in the deoxyadenosine triphosphate level after 4 h incubation in normal phytohaemagglutinin-stimulated lymphocytes. There was a rise in the concentrations of the other three deoxyribonucleoside triphosphates (deoxythymidine-,deoxycytidine-and deoxyguanosine-triphosphate). The changes are similar to those caused by hydroxyurea, a known inhibitor of ribonucleotide reductase. Desferrioxamine (10(-3 M) was found to inhibit human lymphocyte ribonucleotide reductase to a mean of 11% of control activity after 45 min incubation. Both drugs, desferrioxamine and hydroxyurea, inhibited incorporation of [3H]thymidine DNA into lymphocytes in the presence or absence of deoxyuridine, and inhibited production of lymphocytic thymidine kinase, having opposite effects to methotrexate on both [3H]thymidine incorporation and thymidine kinase activity. Phytohaemagglutinin-stimulated lymphocytes from patients with chronic iron deficiency showed lower levels of all our deoxyribonucleoside triphosphates than normal lymphocytes. It is suggested that this may be due to reduced ribnucleotide reductase activity of the iron-deficient 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.

546BRITISH MEDICAL JOURNAL 8 MARCH 1975 noted that electron-dense deposits in electronmicrographs were usually on the "endothelial surface of the glomerular capillary wall." Such lesions were clearly not among those we saw.With regard to the relationship between Q.M.N. and the tropical nephropathy seen in Senegal the similarities lie in the histological features rather than in the immunofluorescence findings. Thus in both conditions a fibrillary change in the capillary wall leads to focal and segmental glomerulosclerosis. Moreover, electronmicrographs show intrusion of basementmembrane-like material into the capillary lumen, which was one of the lesions that White (1973) stressed in Q.M.N. He also reported the presence of curious lacunar areas of basement membrane resorption, at the centre of which were electrondense flecks. These were not noted in the study of Q.M.N. made by Allison etal. (1971), though they described conspicuous electron-dense deposits within the glomerular basement membrane in 12 out of 14 cases, deposits which were not seen by White.In short, the two unusual nephropathies we observed in Senegal differed, despite some similarities, from others hitherto reported in West Africa. One

Cytotoxic and DNA synthesis inhibitory effects of several iron chelators with different physicochemical properties have been tested in four myeloid leukaemic cell lines (U937, K562, ML2 and HL60). The small lipophilic chelators 8-hydroxyquinoline, tropolone and omadine at 2 X 10(-5) M, caused substantial inhibition of labelled leucine and thymidine uptake into cells and also cell death following 4-h incubation. These effects were approximately 10-fold increased when the drugs were pre-incubated with equimolar amounts of iron. Iron alone and hydrophilic chelators e.g. desferrioxamine had insignificant cytotoxic and DNA synthesis inhibitory effects under the same conditions.