Pattanapanyasat K, Webster H K, Tongtawe P, Kongcharoen P, Hider R C
Thalassaemia Centre, Faculty of Graduate Studies, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Br J Haematol. 1992 Sep;82(1):13-9. doi: 10.1111/j.1365-2141.1992.tb04587.x.
Several iron chelators, 3-hydroxypyridin-4-ones (CP) and desferrioxamine (DF) were compared for their effect on DNA synthesis, cell viability and expression of cell proliferation markers. Short-term (4 h) exposure of human peripheral blood mononuclear cells to CP or DF inhibited the proliferative response of cells to concanavalin A (Con A). Inhibition by CP and DF showed a dose-dependent effect with CP compounds more active than DF. Increased inhibitory activity of CP over DF was partly due to the lipophilic properties of CP. Pre-saturation of CP and DF with exogenous ferric ion either diminished or prevented the inhibitory effect. At high chelator concentrations or prolonged (72 h) exposure of the cells to chelators, inhibition occurred but poor cell viability was observed. In contrast to their inhibition of DNA synthesis, these iron chelators showed little effect on protein synthesis and the expression of transferrin receptors and interleukin-2 (IL-2) receptors. These findings suggest that both DF and CP compounds exert their effect by chelation of ferric ion with subsequent inhibition of DNA synthesis.
比较了几种铁螯合剂、3-羟基吡啶-4-酮（CP）和去铁胺（DF）对DNA合成、细胞活力及细胞增殖标志物表达的影响。将人外周血单个核细胞短期（4小时）暴露于CP或DF可抑制细胞对刀豆球蛋白A（Con A）的增殖反应。CP和DF的抑制作用呈剂量依赖性，CP化合物比DF更具活性。CP比DF抑制活性更高部分归因于CP的亲脂性。用外源铁离子对CP和DF进行预饱和可减弱或阻止抑制作用。在高螯合剂浓度或细胞长时间（72小时）暴露于螯合剂的情况下，会出现抑制作用，但观察到细胞活力较差。与它们对DNA合成的抑制作用相反，这些铁螯合剂对蛋白质合成以及转铁蛋白受体和白细胞介素-2（IL-2）受体的表达影响很小。这些发现表明，DF和CP化合物均通过螯合铁离子继而抑制DNA合成发挥作用。
