Abstract
Hematopoietic stem cells are supposed to repopulate and maintain long-term regeneration of the recipient's bone marrow and peripheral blood. In this study, we evaluated the regeneration capability of Lin-/c-Kit+/Sca-1+ (LKS) cells, the putative hematopoietic stem cells, after radiation exposure at graded doses, for long-term regeneration of peripheral blood in lethally irradiated recipients. LKS cells, collected from the bone marrow of C57BL/6 (Ly5.1) mice that had been irradiated at graded increased doses (0.5, 1, 1.5, and 2 Gy) were transfused into lethally irradiated (9.5 Gy) syngeneic Ly5.2 mice. Then, the Ly5.1 chimeric ratio in repopulated peripheral blood cells in the recipients was monitored 35, 90 and 270 days after transfusion. Differential regeneration capability of LKS cells showed a dose-dependent suppression of regeneration of peripheral blood in the recipient mice as compared with LKS cells without radiation exposure. The amount of ROS in LKS cells was much smaller than that in mature bone marrow cells, and that of ROS in LKS increased slightly after radiation exposure. ROS generation after irradiation was attenuated by the treatment with 100 mM NAC before irradiation. Moreover, the amount of ROS generated in LKS cells after radiation exposure was different between progenitor cells for early regeneration and those for late regeneration. These results indicated that hematopoietic progenitor cells regenerating peripheral blood cells 270 days after transfusion were assumed to be more radioresistant than those on day 35 or day 90.
