Hileti D, Panayiotidis P, Hoffbrand A V
Department of Haematology, Royal Free Hospital School of Medicine, London.
Br J Haematol. 1995 Jan;89(1):181-7. doi: 10.1111/j.1365-2141.1995.tb08927.x.
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.
已发现铁螯合剂1,2 - 二甲基 - 3 - 羟基吡啶 - 4 - 酮（L1）和去铁胺（DFO）可诱导增殖活化的T淋巴细胞和早幼粒细胞系HL60凋亡，但对静息外周血淋巴细胞或粒细胞无此作用。通过碘化丙啶对凋亡/死亡细胞染色及流式细胞术对凋亡诱导情况进行定量分析。在与螯合剂以等效铁结合浓度（300μM L1或100μM DFO）孵育24小时的活化T淋巴细胞中，L1使细胞死亡增加54%，DFO使细胞死亡增加57%。在HL60细胞中，L1使细胞死亡增加50%，DFO使细胞死亡增加40%。用任一螯合剂处理的HL60细胞的DNA细胞荧光测定显示，DNA含量低于二倍体的细胞百分比增加。用氯化铁对螯合剂进行预饱和处理可消除这些作用。即使孵育48小时后，L1和DFO也不会诱导静息外周血淋巴细胞或粒细胞凋亡。
