Heavy Ion Beam Irradiation Regulates the mRNA Expression in Megakaryocytopoiesis from Human Hematopoietic Stem/Progenitor Cells
Heavy Ion Beam Irradiation Regulates the mRNA Expression in Megakaryocytopoiesis from Human Hematopoietic Stem/Progenitor Cells
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DOI：
10.1269/jrr.09058
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发表时间：
2009-09-01
影响因子：
2
通讯作者：
Kashiwakura, Ikuo
中科院分区：
文献类型：
--
作者：
Monzen, Satoru;Takahashi, Kenji;Kashiwakura, Ikuo
重离子束是一种高LET辐射，比电子束或X射线具有更大的生物效应。然而，很少有人知道重离子束对人类造血干/祖细胞（HSPCs）的增殖和分化的影响。本研究探讨了重离子束对人HSPCs基因表达的影响，特别是在巨核细胞生成早期。将人CD 34（+）细胞暴露于加速器（千叶的重离子医用加速器）产生的单能碳离子束（290 MeV/核子，LET = 50 KeV/m）。采用实时荧光定量RT-PCR方法分析早期造血、巨核细胞/红细胞生成、细胞因子受体和氧化应激相关基因的表达。早期造血相关基因Friend白血病病毒整合1在照射后6小时的mRNA表达显著高于对照组。与此相反，几乎所有其他早期造血相关基因，细胞因子受体编码基因和巨核细胞生成/红细胞生成分化途径相关基因，分别没有观察到显着差异。对基因对氧化应激的反应的分析显示，血红素加氧酶1的表达在0.5戈伊和2戈伊照射后24小时分别显示出从第0天对照增加1.5倍和11.9倍。类似地，与初始对照相比，NAD（P）H脱氢酶-醌1表达在6小时也显示出22.0倍和21.8倍的增加。这些结果表明，重离子束在基因表达水平上影响了人HSPCs的巨核/红系分化。
Heavy ion beams are a high-LET radiation that has greater biological effect than electron beams or X-rays. However, little is known about the effect of heavy ion beams on the proliferation and differentiation of human hematopoietic stem/progenitor cells (HSPCs). The present study examined the effect of heavy ion beams on gene expression in human HSPCs, especially during early stage of megakary-ocytopoiesis. Human CD34(+) cells were exposed to monoenergetic carbon-ion beams (290 MeV/nucleon, LET = 50 KeV/m) that were generated by an accelerator (Heavy Ion Medical Accelerator in Chiba). The expression of various genes related to early hematopoiesis, megakaryocytopoiesis/erythropoiesis, cytokine receptors and oxidative stress were analyzed by real-time RT-PCR. Friend leukemia virus integration 1, an early hematopoiesis-related gene, showed significantly higher mRNA expression than the control at 6 hr after irradiation. In contrast, no significant differences were observed in almost all of the other early hematopoiesis-related genes, cytokine receptor-coded genes and megakaryocytopoiesis/erythropoiesis-differentiation pathway-related genes, respectively. An analysis of the response of the genes to oxidative stress revealed the expression of heme oxygenase 1 to show a 1.5-fold and 11.9-fold increase from the day 0 control at 24 hr after 0.5 Gy and 2 Gy irradiation, respectively. Similarly, the NAD(P)H dehydrogenase-quinone 1 expression also showed a 22.0-fold and a 21.8-fold increase at 6 hr in comparison to the initial control. These results showed that the heavy ion beams affect megakaryocytopoiesis/ erythropoiesis differentiation of human HSPCs on the gene expression level.