Dose rate effects on the survival of normal hematopoietic stem cells of BALB/c mice.

The use of total body irradiation (TBI) to ablate malignant stem cells in leukemia patients prior to bone marrow transplantation and the use of hemibody irradiation (HBI) for treating osseous metastases have focused attention on the dose rate effects, if any, exhibited by normal or malignant hematopoietic stem cells. Using male BALB/c mice 10 to 12 weeks old, we investigated dose rate effects at 103, 45 and 8 rad/min over the dose range from 100 to 500 rad. Bone marrow cells from the femurs of irradiated donor mice were transplanted into lethally irradiated (720 rad) mice of the same age, sex, and strain. Recipient mice were sacrificed 9 days later, their spleens fixed, stained with Bouin's solution, and the macroscopic colonies counted to determine the number of colony forming units (CFU) per femur. Surviving fractions were determined by comparisons to the CFU's of non-treated controls. The logarithms of the surviving fractions, S, versus dose, D, (in rad) were least squares fitted and the extrapolation number, n, and D0 obtained. The extrapolation numbers ranged from 0.65 +/- 0.15 to 0.81 +/- 0.08, and D0 ranged from 61.7 +/- 3.4 to 69.0 +/- 2.8. There are no statistically significant differences between the n's and D0's for these different dose rates over the dose range from 100 to 500 rad, as measured by spleen CFU assay of normal femoral marrow. The D0's are appropriate for this radiosensitive mouse strain. These data are compared to those from other studies using the same method of CFU assay.