Nishi N, Osawa M, Ishikawa R, Nishikawa M, Tsumura H, Inoue H, Sudo T
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
Stem Cells. 1995 Sep;13(5):517-23. doi: 10.1002/stem.5530130509.
It is known that treatment of mice with 5-fluorouracil (5-FU, 150 mg/kg) confers radioprotection. To investigate this effect, we performed bone marrow transplantation (BMT) using C57BL/6-Ly5 congenic mice treated with 5-FU five days prior to experiments. The mononuclear cells (MNC) in 5-FU-treated bone marrow (BM) were 10 times more radioprotective than those in untreated BM. Moreover, the number of BM MNC expressing c-kit on their surface from 5-FU-treated mice was markedly decreased relative to those from untreated controls. These results showed that the surface characteristics of cells that contributed to this radio-protective effect differ from those of stem cells as reported recently. BM MNC of mice treated with 5-FU were separated on the basis of expression of the lineage-specific antigens (Lin), c-kit, and Ly6A/E. When injected into lethally irradiated mice, 1,000 Lin+ and Lin-c-kit+Ly6A/E+ cells showed radioprotective effects such that 100% and 60% survived, respectively. Flow cytometric analysis 165 days after BMT showed that 88.8% and 65.1% of peripheral blood (PB) in mice transplanted with Lin+ and Lin-c-kit+Ly6A/E+ was derived from donor mice, respectively. After six months, donor-derived Lin-c-kit+Ly6A/E+ cells which showed radioprotective effects on a secondary irradiated host were detected from mice transplanted with Lin+ cells from 5-FU-treated mice. Taken together, these findings demonstrated that stem cells expressing Lin+ present in the BM of mice treated with 5-FU other than Lin-c-kit+Ly6A/E+ cells and these Lin+ cells play an important role in the recovery of myeloablative mice.
已知用5-氟尿嘧啶（5-FU，150毫克/千克）处理小鼠可赋予辐射防护作用。为研究这种效应，我们使用在实验前五天用5-FU处理的C57BL/6-Ly5同基因小鼠进行了骨髓移植（BMT）。5-FU处理的骨髓（BM）中的单核细胞（MNC）的辐射防护能力比未处理的BM中的单核细胞强10倍。此外，与未处理的对照相比，5-FU处理小鼠的表面表达c-kit的BM MNC数量明显减少。这些结果表明，促成这种辐射防护作用的细胞的表面特征与最近报道的干细胞的表面特征不同。根据谱系特异性抗原（Lin）、c-kit和Ly6A/E的表达对5-FU处理小鼠的BM MNC进行分离。当将1000个Lin+和Lin-c-kit+Ly6A/E+细胞注射到接受致死剂量照射的小鼠中时，它们显示出辐射防护作用，存活率分别为100%和60%。BMT后165天的流式细胞术分析表明，移植了Lin+和Lin-c-kit+Ly6A/E+细胞的小鼠外周血（PB）中分别有88.8%和65.1%来自供体小鼠。六个月后，从移植了5-FU处理小鼠的Lin+细胞的小鼠中检测到对二次照射宿主具有辐射防护作用的供体来源的Lin-c-kit+Ly6A/E+细胞。综上所述，这些发现表明，5-FU处理小鼠的BM中存在的除Lin-c-kit+Ly6A/E+细胞之外的表达Lin+的干细胞，并且这些Lin+细胞在清髓性小鼠的恢复中起重要作用。
