Forced differentiation of CFU-S by Iron-55 erythrocytocide.
Forced differentiation of CFU-S by Iron-55 erythrocytocide.
复制标题
通过 Iron-55 红细胞杀灭剂强制分化 CFU-S。
DOI：
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发表时间：
1979
期刊：
影响因子：
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通讯作者：
E. Cronkite
中科院分区：
文献类型：
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作者：
U. Reincke;D. Brookoff;H. Burlington;E. Cronkite
在55Fe的衰变过程中，俄歇电子级联发射，并在1微米半径内的组织中被吸收。因此，杀伤细胞量的55Fe可以在对邻近细胞损伤最小的情况下消除红细胞前体。单次静脉注射导致小鼠持续的红细胞杀伤，因为同位素被重新利用，半衰期为2.7年。细胞杀灭剂唤起了形态上不可识别的前体的早期代偿反应，这些前体分化为原母细胞。这些早期事件不影响颗粒序列，但伴随着骨髓、脾脏和血液中多能干细胞（CFU-S）数量的急剧下降。CFU-S未恢复预处理水平。CFU-S的逐渐下降与间歇性增加的周转率和细胞产生的减少有关，但快速恢复失血的能力并未受损。正如使用冷冻储存细胞杀剂技术的单独实验系列所显示的那样，最初的干细胞急剧减少不是由辐照损伤引起的。只有在几周内，55Fe辐射才能在未分裂的干细胞中积累到致死水平。这种辐照是由于少量的55Fe掺入CFU-S，并从那里慢慢清除。在我们的解释中，注射55Fe后立即发生的干细胞损失是由红系途径的快速分化引起的，这一反应涉及所有祖细胞群体。数据与细胞更新能力有限的假设一致，从而获得进一步的支持。
Cascades of Auger electrons are emitted in the decay of 55Fe and absorbed in tissue within a 1 micrometer radius. Cytocidal amounts of 55Fe can therefore eliminate erythroid precursors with minimal damage to adjacent cells. A single intravenous injection leads to continued erythrocytocide in mice because the isotope is reutilized and has a 2.7 year half-life. The cytocide evokes an early compensatory response from morphologically unrecognizable precursors which differentiate into pronormoblasts. These early events leave the granuloid series undisturbed but they are accompanied by a precipitous fall in pluripotent stem cell (CFU-S) numbers in bone marrow, spleen, and blood. The pretreatment levels of CFU-S are not restored. Gradual decline of CFU-S is associated with intermittently increased turnover rates and reduced settings of cell production, yet the capacity for quick restoration of blood loss is unimpaired. The precipitous initial stem cell decrease is not caused by irradiation damage, as shown in a separate experimental series that used the frozen-storage cytocide technique. Only over several weeks could 55Fe radiation accumulate to lethal levels in nondividing stem cells. This irradiation is attributed to incorporation of small amounts of 55Fe into CFU-S, from where it is slowly cleared. The stem cell loss immediately following 55Fe injection is in our interpretation caused by rapid differentiation along the erythroid pathway in a response that involves all progenitor populations. Data are consistent with the hypothesis of limited cell renewal capacity which thereby gains further support.