Nocka K H, Pelus L M
Department of Hematopoietic Regulation, Sloan-Kettering Institute, New York, New York 10021.
Cancer Res. 1988 Jul 1;48(13):3571-5.
The effect of the iron chelator deferoxamine (DSF) on the proliferation of normal erythroid and granulocyte-macrophage progenitor cells from human and murine bone marrow was examined. The addition of DSF at a concentration equivalent to the concentration of iron present in the culture system resulted in dose dependent inhibition of colony formation by human and murine granulocyte-macrophage progenitor cells and human normal erythroid progenitor cells. The addition of FeCl3 at culture initiation completely reversed the effects of DSF. Furthermore, significant numbers of progenitor cells could be rescued from the effects of DSF by iron added back as late as 24-48 h after exposure to DSF. The cell cycle specificity of DSF was also examined using bone marrow cells treated with high specific activity tritiated thymidine. Kinetic experiments demonstrated that in the presence of DSF the number of erythroid or granulocyte-macrophage colonies that could be rescued was dependent on the length of exposure to DSF. Comparisons between control and tritiated thymidine treated cells indicated that the proliferation of progenitor cells in S phase of the cell cycle was inhibited if iron was withheld until 6 and 24 h after exposure to DSF for murine and human cells, respectively, with little to no effect observed on progenitor cells not in S phase during this time period. These results confirm the importance of iron for hematopoietic progenitor cell proliferation and represent a new method by which the proliferation of cycling cells may be investigated in situ in semisolid culture systems.
研究了铁螯合剂去铁胺（DSF）对人及小鼠骨髓中正常红系和粒-巨噬系祖细胞增殖的影响。添加浓度相当于培养系统中铁浓度的DSF，会导致人及小鼠粒-巨噬系祖细胞和人正常红系祖细胞的集落形成呈剂量依赖性抑制。在培养开始时添加FeCl₃可完全逆转DSF的作用。此外，在暴露于DSF后最晚至24 - 48小时添加铁，可使大量祖细胞从DSF的影响中挽救出来。还使用用高比活度氚标记胸腺嘧啶处理的骨髓细胞检测了DSF的细胞周期特异性。动力学实验表明，在存在DSF的情况下，能够挽救的红系或粒-巨噬系集落数量取决于暴露于DSF的时间长度。对照细胞与氚标记胸腺嘧啶处理细胞之间的比较表明，如果分别在小鼠和人细胞暴露于DSF后6小时和24小时停止供应铁，细胞周期S期的祖细胞增殖会受到抑制，而在此时间段内对非S期的祖细胞几乎没有影响。这些结果证实了铁对造血祖细胞增殖的重要性，并代表了一种在半固体培养系统中原位研究循环细胞增殖的新方法。
