Involvement of intracellular reactive oxygen species and mitochondria in the radiosensitivity of human hematopoietic stem cells.

Reactive oxygen species (ROS) can cause significant biological damage and are produced from low linear energy transfer-ionizing radiation, such as X-rays. Although hematopoietic stem cells (HSCs) are known to be particularly sensitive to ionizing radiation, little is known about the roles of mitochondria and ROS production in determining the radiosensitivity of HSCs. The clonogenic survival of CD34(+) HSCs, intracellular mitochondrial content, and intracellular ROS production after irradiation were investigated to elucidate the involvement of mitochondria and ROS in the individual radiosensitivity of HSCs detected in human placental/umbilical cord blood. The results showed that large individual differences exist in the initial numbers of each progenitor cell type, as well as in the surviving fraction of cells. When supplemented with an appropriate cytokine combination, a statistically significant increase in ROS production was observed at 3 h after 2 or 4 Gy of irradiation (P < 0.05), with nearly a return to initial levels by 6 h. In contrast, no significant difference was observed under cytokine-free conditions. At this stage, no significant correlations were observed between ROS production, intracellular mitochondrial content, and the surviving fractions of each HSC progenitor. These results suggest that the kinetics of ROS generation during the 6 h after ionizing radiation have little effect on the different radiation sensitivity of HSCs.