title: Characteristics of human CD34+ cells exposed to ionizing radiation under cytokine-free conditions.
abstract: To clarify the mechanisms underlying radiation-induced hematopoietic stem cell death, we investigated the effects of excessive ionizing radiation on the clonogenic potential of CD34(+) cells obtained from human umbilical cord blood under cytokine-free conditions. The CD34(+) cells were X-ray-irradiated (up to 2 Gy) and were cultured for 0-48 h under cytokine-free conditions. At various time-points, the CD34(+) cells were investigated for survival, clonogenic potential and the generation of mitochondrial superoxide. At 12 h after X-ray irradiation, the number of viable cells had decreased to ∼70-80% compared with the 0-h non-irradiated control, whereas the clonogenic potential in the X-ray-irradiated cells had decreased to ∼50%-60% compared with the 0-h non-irradiated control. Furthermore, significant generation of mitochondrial superoxide was observed at 6 h, and reached a maximum value between 12 and 24 h after X-ray irradiation. However, no significant differences were observed between non-irradiated and X-ray-irradiated cells in terms of the generation of reactive oxygen species or in the intracellular mitochondrial contents. In addition, a cDNA microarray analysis showed that the majority of the altered genes in the CD34(+) cells at 6 h after X-ray irradiation were apoptosis-related genes. These results suggest the possibility that the elimination of the clonogenic potentials of CD34(+) cells involves the generation of mitochondrial superoxide induced by ionizing radiation.
authors: Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8203, Japan.
authors: Junya
authors: J
authors: Ishikawa
authors: Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8203, Japan.
authors: Naoki
authors: N
authors: Hayashi
authors: Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8203, Japan.
authors: Masaru
authors: M
authors: Yamaguchi
authors: Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8203, Japan.
authors: Satoru
authors: S
authors: Monzen
authors: Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8203, Japan ikashi@cc.hirosaki-u.ac.jp.
authors: Ikuo
authors: I
authors: Kashiwakura
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology* / Q000528:radiation effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D006801:Humans; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D016207:Cytokines; D017382:Reactive Oxygen Species
keywords: CD34+ cells; clonogenic potential; radiation; superoxide