title: Severe damage of human megakaryocytopoiesis and thrombopoiesis by heavy-ion beam radiation.
abstract: 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.
authors.affiliation: Department of Bio-information Radiation Sciences, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8564, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takahashi
authors.forename: Satoru
authors.initials: S
authors.lastname: Monzen
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Eguchi-Kasai
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Abe
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kashiwakura
mesh_terms: D002454:Cell Differentiation / Q000528:radiation effects*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D020450:Heavy Ions; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D006801:Humans; D011829:Radiation Dosage; D034061:Thrombopoiesis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects*
chemical_list: D016207:Cytokines