A cellular analysis of residual hemopoietic deficiencies in mice after 4 repeated doses of 4.5 Gray X rays.

A sub-optimal plateau in numbers of femoral stem-cells (CFU-S) in mice after 4 doses of 4.5 Gray X rays (each separated by 21 days), was shown to persist at 20-30% of control up to 1 year after the last dose, when about 50% of the mice had survived. The concentration of white cells in the blood was maintained persistently at about 70% of control, whereas the concentration of red cells was normal up to 4 months and then it declined to about 75% of control at 10 months after irradiation. Concentrations of some committed progenitor cells in the marrow (GM-CFC and ERC), which are capable of amplification cell divisions, were intermediate between the concentrations of marrow stem cells and mature blood cells in both the granuloid and the erythroid cell lineages, respectively. Hence increased amplification was a mechanism operating for a prolonged period in the production of numbers of mature cells. The numbers were subnormal, however, and this corresponded to only 1 extra amplification division on average. There was a slow decline after 6 months in the numbers of CFU-S, BFU-E and GM-CFC, and in the hematocrit, with reference to age-matched controls. The decline was due partly to a prevention of the natural increase in cell numbers in the marrow with the age of the mice, which was also seen with the femoral content of a stromal progenitor cell (CFU-F). A defect in the repeatedly-irradiated CFU-S population was detected as a persistent inability to produce colonies containing the same number of daughter CFU-S as contained in colonies derived from unirradiated marrow and assayed at the same time.