Differing Patterns of Erythropoiesis Following Whole-Body Irradiation in W/W v and SL/SL d Mice

In normal mice given whole-body irradiation the time of onset of postirradiation erythropoiesis is directly proportional to the radiation dose suggesting that the damaged pluripotent hematopoietic compartment tends first to regenerate to a certain level before it differentiates. The present study was done to determine whether or not hematopoiesis in two mouse models of hypoplastic anemia responded to damage in the same way. Onset of postirradiation hematopoiesis was determined by repeated reticulocyte counts in individual mice. In ${\rm W}/{\rm W}^{{\rm v}}$ mice the pattern of recovery of reticulocytes after 100 or 200 rad followed a predictable pattern with a nadir of 0 to 0.3% followed by a sustained rise occurring around 5.7 and 6.3 days after 100 rad in two experiments, 6.9 days after 150 rad and 10.6 days after 200 rad. Thus there was an average delay of onset of increasing reticulocytes of 3.4 days for each increment of 100 rad in ${\rm W}/{\rm W}^{{\rm v}}$ mice as compared to a delay of 1.1 days in +/+ littermate controls. Similar studies were done with ${\rm SL}/{\rm SL}^{{\rm d}}$ mice, though their +/+ littermate controls given 200 and 300 rad yielded virtually identical results to those of the controls for ${\rm W}/{\rm W}^{{\rm v}}$ mice. The ${\rm SL}/{\rm SL}^{{\rm d}}$ mice given 50 to 150 rad have very unpredictable postirradiation reticulocyte changes. Neither nadir nor time of increase was constant from mouse to mouse. All mice given 125 rad or more died and in survivors of 100 rad reticulocytosis was not sustained over the period of study. Furthermore, there was no evident relationship between the amount of irradiation and reticulocyte nadir. This is in contrast to the ${\rm W}/{\rm W}^{{\rm v}}$ and both +/+ littermate control groups, where increasing doses of irradiation invariably led to a progressive decrease in the reticulocyte nadir. Thus for ${\rm W}/{\rm W}^{{\rm v}}$ mice the pattern of decline and subsequent increase following whole-body irradiation is qualitatively similar to that of normal +/+ littermate control mice but the delay in onset of erythropoiesis is longer per rad in the ${\rm W}/{\rm W}^{{\rm v}}$ mice. This and other data on the ${\rm W}/{\rm W}^{{\rm v}}$ mice suggest that their defect in hematopoiesis might best be explained by slow growth or slow onset of growth of pluripotent stem cells after stimulation. The pattern for ${\rm SL}/{\rm SL}^{{\rm d}}$ mice was qualitatively different than the other mice. It would appear that the pluripotent stem cells of ${\rm SL}/{\rm SL}^{{\rm d}}$ mice continue to differentiate after irradiation even though the dose proves to be lethal.