Takahashi Kenji, Monzen Satoru, Eguchi-Kasai Kiyomi, Abe Yoshinao, Kashiwakura Ikuo
Department of Bio-information Radiation Sciences, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8564, Japan.
Radiat Res. 2007 Nov;168(5):545-51. doi: 10.1667/rr1008.1.
Heavy ions have a unique efficacy for tumor control in radiotherapy. To clarify the effects of heavy-ion beams on hematopoietic stem/progenitor cells, the effects of carbon-ion beams on megakaryocytopoiesis and thrombopoiesis in CD34(+) cells derived from human placental and umbilical cord blood were investigated. The cells were exposed to carbon-ion beams (LET = 50 keV/microm) and then were treated with thrombopoietin (TPO) alone or TPO plus other cytokines. Megakaryocytic progenitor cells, such as megakaryocyte colony-forming units (CFU-Meg), were far more sensitive to carbon-ion beams than to X rays, and no restoration of carbon-ion beam-irradiated CFU-Meg by treatment with any cytokine combination was observed. However, total cell expansion in liquid culture was not different after either carbon-ion beam or X irradiation of CD34(+) cells. The activation of gamma-H2AX, a marker of DNA double strand-breaks (DSBs), was promoted by the cytokine treatment in X-irradiated CD34(+) cells but not in carbon-ion-irradiated cells. These results showed that carbon-ion beams inflicted severe damage on megakaryocytopoiesis and thrombopoiesis and that a better combination of cytokines and other agents may be needed to stimulate the recovery of hematopoietic cells and repair this damage.
重离子在放射治疗中对肿瘤控制具有独特的疗效。为了阐明重离子束对造血干/祖细胞的影响，研究了碳离子束对源自人胎盘和脐带血的CD34(+)细胞中巨核细胞生成和血小板生成的影响。将细胞暴露于碳离子束（传能线密度=50 keV/μm），然后单独用血小板生成素（TPO）或TPO加其他细胞因子进行处理。巨核细胞祖细胞，如巨核细胞集落形成单位（CFU-Meg），对碳离子束的敏感性远高于对X射线的敏感性，并且未观察到用任何细胞因子组合处理能使经碳离子束照射的CFU-Meg恢复。然而，对CD34(+)细胞进行碳离子束或X射线照射后，液体培养中的总细胞扩增并无差异。DNA双链断裂（DSB）的标志物γ-H2AX的激活在经X射线照射的CD34(+)细胞中通过细胞因子处理得到促进，但在经碳离子照射的细胞中未得到促进。这些结果表明，碳离子束对巨核细胞生成和血小板生成造成了严重损伤，可能需要更好地组合细胞因子和其他药物来刺激造血细胞的恢复并修复这种损伤。
