The identification of factor (s) which regulate individual radiosensitivity of human hematopoietic stem/progenitor cells and its application

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The purpose of this study was to clarify the individual radiosensitivity of human hematopoietic stem/progenitor cells and the relation between the characters of cell surface antigens, proliferative potentials and gene expressions, thus identifying what is the factor (s) to regulate the individual radiosensitivity of human hematopoietic stem cells. The following points were revealed.1. It suggest that the radiosensitivity of individual hematopoietic stem/progenitor cells (HSPCs) is related to the number of progenitor cells in the CD34^+ cells especially dependent on the presence of immature HSPCs such as Tie-2^+ cells.2. The mRNA expression of Nrf2 target genes such as HO-1, FTH1, NQO1, GSR and TXNRD1 was significantly increased after 2 Gy X irradiation. A statistically significant negative correlation was observed between the surviving fraction of HSPCs and the intrinsic NQO1 mRNA expression, indicating that HSPCs in which NQO1 mRNA levels are low may also be radioresistant. The present results suggest that the antioxidant system associated with Nrf2 is involved in the radiosensitivity of HSPCs.3. A significant correlation was observed between the surviving fraction of hematopoietic progenitor cells obtained after 0.5 Gy irradiation and the age of the blood donors. In particular, this correlation was more evident in males, with a correlation coefficient of-0.318 (P=0.043). A correlation between the individual responsiveness of hematopoietic progenitor cells to ionizing irradiation, particularly to a low-dose of irradiation (such as 0.5 Gy), and aging has been established.