Most primitive hematopoietic stem cells are stimulated to cycle rapidly after treatment with 5-fluorouracil.
Most primitive hematopoietic stem cells are stimulated to cycle rapidly after treatment with 5-fluorouracil.
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DOI：
10.1182/blood.v78.5.1237.bloodjournal7851237
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发表时间：
1991-09
期刊：
影响因子：
20.3
通讯作者：
David E. Harrison;C. Lerner
中科院分区：
文献类型：
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作者：
David E. Harrison;C. Lerner
为了检测原始造血干细胞(PHSC)在最初的5-氟尿嘧啶(5-FU)治疗恢复过程中是否快速循环，分别在1、3、5或8天内给予两次5-FU。来自经过治疗的骨髓捐赠者的细胞与未经治疗的竞争骨髓混合，使用血红蛋白(Hb)和葡萄糖磷酸异构酶(GPI)移植标记，这些骨髓将产生遗传上可区分的红细胞和淋巴细胞。这些细胞混合物被注射到受到致死照射的宿主体内。在3、6和12个月后，分别以供者红细胞和淋巴细胞中供者Hb和GPI的百分比来评估供者骨髓群体的功能。间隔3至5天接受两次5-FU治疗的小鼠的骨髓受到严重影响，每隔3天产生的循环红系和淋巴样细胞平均只有正常的25%，而每隔5天产生的循环红系和淋巴样细胞平均只有正常的14%。间隔1天或8天服用两次5-FU的效果要小得多，产生的循环细胞是正常的75%或58%。因此，大多数PHSC在5-FU治疗后3-5天被刺激迅速增殖，但很少有PHSC在5-FU治疗后1天或晚8天增殖。
To test whether primitive hematopoietic stem cells (PHSC) cycle rapidly during recovery from an initial 5-fluorouracil (5-FU) treatment, two doses of 5-FU were administered 1, 3, 5 or 8 days apart. Cells from treated marrow donors were mixed with untreated competitor marrow that would produce genetically distinguishable erythrocytes and lymphocytes, using hemoglobin (Hb) and glucosephosphate isomerase (GPI) transplantation markers. These cell mixtures were injected into lethally irradiated hosts. Functional abilities of donor marrow populations were assessed after 3, 6, and 12 months as percentages of donor type Hb and GPI in the host's circulating erythrocytes and lymphocytes, respectively. Bone marrow from mice treated with two doses of 5-FU 3 to 5 days apart was severely affected, producing circulating erythroid and lymphoid cells an average of only 25% of normal for doses 3 days apart, and 14% of normal for doses 5 days apart. Two doses of 5-FU administered 1 day or 8 days apart had much smaller effects, producing circulating cells 75% or 58% of normal. Thus, most PHSC are stimulated to proliferate rapidly 3 to 5 days after treatment with 5-FU, but far fewer PHSC proliferate as early as 1 day, or as late as 8 days, after the 5-FU treatment.