K.H. Steinbach

The radiosensitivity of the granulopoietic progenitor cells (GM-CFC) from blood and bone marrow of dogs under steady state conditions was studied by in vitro irradiation with 280kV X-rays (approximately 0.56 Gy/min). The dose-effect relationship for colony formation was determined for the dose range from 0 to 3 Gy by means of three different models. A simple exponential function revealed an optimal approximation to the experimental data obtained for the clonogenic cells from the two different sources. The D0 values are 0.261 +/- 0.009 Gy and 0.600 +/- 0.011 Gy for the GM-CFC from blood and bone marrow, respectively. Irradiation of blood-derived GM-CFC in the presence of pre-irradiated bone marrow cells or irradiation of bone marrow cells as a mixture with pre-irradiated blood cells led to small changes only in the survival curves. According to the dose-effect relationship obtained from these studies the GM-CFC of the dog seem to be the most radiosensitive clonogenic haemopoietic cells among the different mammals.

The restoration of the granulocyte-macrophage progenitor cell (CFU-GM) compartments in blood and bone marrow, and the recovery of blood monocytes were followed for up to one year in ten beagles that had been exposed to fractionated (3 X 6 Gy) total-body irradiation before being transfused with cryopreserved fetal liver cells (FLC) from sibling donors that were genotypically matched for dog leukocyte antigens. Grafts contained 0.2-1.6 X 10(8) mononuclear cells and 0.9-19.8 X 10(4) CFU-GM/kg body weight. Numbers of circulating monocytes rose parallel to granulocyte numbers after day 6 and became normal by day 18 posttransplant. In bone marrow aspirates, low numbers of CFU-GM were detected on day 3 and their incidence per 10(5) mononuclear cells was normal after day 14. Circulating CFU-GM were present in significant numbers by day 7 and their elevated concentration per milliliter of blood after day 14 continued for one year. Dextran sulfate injection mobilized normal numbers of CFU-GM into the blood early after transplantation, and spontaneously circulating CFU-GM in a later phase did not differ from blood progenitors of normal animals with respect to radiation sensitivity and sedimentation velocity. Thus, FLC transplantation effected a rapid restoration of granulopoiesis and monocytopoiesis, which was reflected at both the level of mature blood cells and the compartments of CFU-GM in blood and bone marrow, underlining the high repopulating capacity of fetal liver stem cells.