Hematopoietic stem/progenitor cells (HSPCs) can self-renew and differentiate into all hematopoietic lineages, and are extremely sensitive to oxidative stresses. Exposure of HSPCs to ionizing radiation causes a marked suppression of mature blood cell production in a dose- dependent manner. However, little information about the long-term effects of low-dose X-irradiation on the stemness of human HSPCs has been reported. The present study investigated the biological characteristics of the differentiation and proliferation of low-dose X-irradiated human CD34 + HSPCs. Highly purified CD34 + cells exposed to low-dose X-rays were cultured in liquid and semisolid media supplemented with an optimal cytokine combination. The liquid medium was cultured for 14 days; no significant differences in total cell number were observed between non- irradiated and X-irradiated cultures. The expression levels of cell surface antigens such as CD34, CD38, and CD45 on cells harvested from X-irradiated culture were similar to those of cells from non-irradiated culture. However, a significant reduction was observed in the number of burst- forming unit erythroid (BFU-E) cells between non-irradiated and 0.5 Gy X-irradiated cells in the myeloid progenitor assay on day 14; moreover, concurrently, radiation-induced γ-H2AX foci were significantly greater on day 14 than on day 0. These results suggest that low-dose X-irradiation is associated with clonal growth suppression of BFU-E cells. Key words: hematopoietic stem/progenitor cells, low-dose X-irradiation, radiosensitivity, burst- forming unit erythroid cells Radiation Emergency Medicine 2013 Vol. 2 No. 2 56-62 Proliferation and Differentiation of Human Hematopoietic Stem/Progenitor Cells Exposed to Low-dose X-irradiation Masaru Yamaguchi, Satoko Ebina and Ikuo Kashiwakura * Department of Radiological Life Sciences, Division of Medical Life Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564, Japan. Received 23 February 2013; accepted 29 March 2013 *Ikuo Kashiwakura, Ph.D.: Department of Radiological Life Sciences Hirosaki University Graduate School of Health Sciences 66-1 Hon-cho, Hirosaki 036-8564, Japan E-mail: ikashi@cc.hirosaki-u.ac.jp Copyright © 2013 by Hirosaki University. All rights reserved. Regular Article 1. Introduction Ionizing radiation with low-linear energy transfer such as X-rays generates reactive oxygen species (ROS) by indirect action of energy on water molecules and simultaneously generating double-strand breaks (DSBs), which are known to be lethal, by direct action on DNA itself, with sequence apoptosis or stress-related responses. The biological effects of low-dose irradiation have been investigated, and the cumulative evidence suggests that the cellular response induced by low-dose irradiation may differ from that induced by higher doses. 1-4) Radiation- induced bystander effects, radioadaptive response, and activation of the defense system or immune response represent phenomena that have an important impact on novel biological responses induced by low-dose irradiation. Hematopoietic stem/progenitor cells (HSPCs) can differentiate into all hematopoietic lineages throughout the lifetime of an organism and self-renew to maintain