Lerner C, Harrison D E
Jackson Laboratory, Bar Harbor, ME 04609.
Exp Hematol. 1990 Feb;18(2):114-8.
The long-term immunohemopoietic reconstituting ability of bone marrow, treated with a single administration of 5-fluorouracil (5-FU), was measured to determine whether 5-FU caused any deleterious effect upon primitive stem cells (PSCs). Cells from 5-FU-treated marrow donors were mixed in four different proportions of total marrow contents with untreated competitor marrow containing genetically distinguishable hemoglobin (Hb) and glucosephosphate isomerase (GPI) transplantation markers. These cell mixtures were introduced into lethally irradiated hosts. The functional ability of the donor cell population was assessed by measuring the percentage of donor type Hb and GPI found in the host's circulating erythrocytes and lymphocytes, respectively. Bone marrow from mice treated with 5-FU 1, 5, and 8 days prior to transplantation produced circulating lymphoid and erythroid cells as well as equal fractions of untreated fresh marrow when surveyed approximately 90 days after transplantation. Normal reconstitutive ability was thus maintained despite a tenfold reduction in marrow cell numbers when donor mice had been treated with 5-FU 5 days prior to transplantation. Donor marrow treated with 5-FU 15 days prior to transplantation had slightly decreased repopulating ability in one of two experiments. A second round of repopulation was stimulated subsequent to the initial 90-day screening by giving hosts a sublethal (500 rad) dose of irradiation. After 3-4 months, Hb and GPI parameters were the same as preirradiation values. Thus, the radioresistance of 5-FU treated PSCs remains comparable to that of fresh marrow, and their relative repopulating ability was not comprised by the additional stress of sublethal irradiation. After both rounds of repopulation the myeloid and lymphoid pathways were repopulated equally well by PSCs surviving 5-FU treatment. Repopulation of both pathways to the same extent suggests a common precursor as the proliferative agent. These results indicate that the PSCs were unaffected after a single treatment with 5-FU, although they were concentrated tenfold.
为了确定5-氟尿嘧啶（5-FU）单次给药是否会对原始干细胞（PSC）产生任何有害影响，对经5-FU处理的骨髓的长期免疫造血重建能力进行了检测。将来自5-FU处理的骨髓供体的细胞与含有基因可区分的血红蛋白（Hb）和葡萄糖磷酸异构酶（GPI）移植标记物的未处理竞争骨髓以四种不同的总骨髓含量比例混合。将这些细胞混合物引入经致死性照射的宿主中。通过分别测量宿主循环红细胞和淋巴细胞中供体类型Hb和GPI的百分比来评估供体细胞群体的功能能力。在移植后约90天进行检测时，移植前1、5和8天用5-FU处理的小鼠的骨髓产生了循环淋巴细胞和红细胞，以及与未处理的新鲜骨髓相同比例的细胞。因此，尽管当供体小鼠在移植前5天用5-FU处理时骨髓细胞数量减少了十倍，但仍保持了正常的重建能力。在两个实验中的一个中，移植前15天用5-FU处理的供体骨髓的再增殖能力略有下降。在最初的90天筛选后，通过给宿主亚致死剂量（500拉德）的照射来刺激第二轮再增殖。3-4个月后, Hb和GPI参数与照射前的值相同。因此，经5-FU处理的PSC的放射抗性与新鲜骨髓的放射抗性相当，并且它们的相对再增殖能力不受亚致死照射的额外压力影响。在两轮再增殖后，经5-FU处理存活的PSC对髓系和淋巴系途径的再填充效果同样良好。两条途径以相同程度再填充表明存在一种共同的前体作为增殖剂。这些结果表明，PSC在单次用5-FU处理后未受影响，尽管它们被浓缩了十倍。
