title: Expression analysis of radiation-responsive genes in human hematopoietic stem/progenitor cells.
abstract: To clarify the nature of the genes that contribute to the radiosensitivity of human hematopoietic stem/progenitor cells (HSPCs), we analyzed the gene expression profiles detected in HSPCs irradiated with 2 Gy X-rays after culture with or without an optimal combination of hematopoietic cytokines. Highly purified CD34(+) cells from human placental/umbilical cord blood were used as HSPCs. The cells were exposed to 2 Gy X-irradiation and treated in serum-free medium under five different sets of conditions for 6 h. The gene expression levels were analyzed by cDNA microarray, and then the network of responsive genes was investigated. A comprehensive genetic analysis to search for genes associated with cellular radiosensitivity was undertaken, and we found that expression of the genes downstream of MYC oncogene increased after X-irradiation. In fact, the activation of MYC was observed immediately after X-irradiation, and MYC was the only gene still showing activation at 6 h after irradiation. Furthermore, MYC had a significant impact on the biological response, particularly on the tumorigenesis of cells and the cell cycle control. The activated gene regulator function of MYC resulting from irradiation was suppressed by culturing the HSPCs with combinations of cytokines (recombinant human thrombopoietin + interleukin 3 + stem cell factor), which exerted radioprotective effects. MYC was strongly associated with the radiosensitivity of HSPCs, and further study and clarification of the genetic mechanisms that control the cell cycle following X-irradiation are required.
authors.affiliation: Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori, Japan.
authors.forename: Takakiyo
authors.initials: T
authors.lastname: Tsujiguchi
authors.affiliation: Department of Radiobiology, Institute for Environmental Sciences, Rokkasho, Aomori, Japan.
authors.forename: Tokuhisa
authors.initials: T
authors.lastname: Hirouchi
authors.affiliation: Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Monzen
authors.affiliation: University of Toyama Life Science Research Center, Toyama, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tabuchi
authors.affiliation: University of Toyama Graduate School of Science and Engineering for Research Life, Toyama, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takasaki
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori, Japan ikashi@hirosaki-u.ac.jp.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kashiwakura
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D002470:Cell Survival / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000528:radiation effects*; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D011827:Radiation; D014965:X-Rays
chemical_list: D018952:Antigens, CD34; D016207:Cytokines; D016271:Proto-Oncogene Proteins c-myc
keywords: gene expression; hematopoietic stem and progenitor cells; radiosensitivity; umbilical cord blood