Radiation Sensitivity of the Hemopoietic Stem Cell

Abstract

The LD50/30 after total-body irradiation (TBI) indicates the radiosensitivity of any animal species and is determined by the number and radiosensitivity of the hemopoietic stem cells, in particular those that are pluripotent. The most extensive information exists for the mouse because in the species the pluripotential stem cells can be enumerated by the spleen colony assay. Stem cells of various species can also be quantified in vitro by the CFU-S and CFU-C assays. With the latter assay, the reported values for D0 and N vary by factors of 2-3 and up to 5, respectively. In both assays the upper level of the range of doses is about 5 Gy. A theoretical approach for the calculation of the D0 of hemopoietic stem cells was previously developed by comparing the number of autologous or syngeneic bone marrow cells required to protect 50% of supralethally irradiated animals with the known LD50/30 of the species and the estimates of total number of bone marrow cells present before irradiation. Using the rate of repopulation of peripheral blood cells in monkeys following high-dose TBI and the repopulation of the spleen and the bone marrow in mice, we have derived estimates of the surviving fractions of hemopoietic stem cells at radiation doses between 5 and 10 Gy. The resulting data suggest, among other possibilities, the presence of a small subpopulation of hemopoietic stem cells with higher radioresistance than the majority of the stem cells. It was postulated that this small subpopulation may exist under hypoxic conditions. To test this hypothesis, RBEs for fission neutrons have been determined for CFU-S survival and for LD50/30 in BCBA mice. Both RBEs were very similar, which proves that the radioresistance of the subpopulation responsible for survival at high doses is not due to hypoxic conditions.