Influence of Dose on Regeneration of Murine Hematopoietic Stem Cells after Total Body Irradiation and 5-Fluorouracil

The regeneration of murine bone marrow stem cells after treatment with 5-fluorouracil (5-FU) and total body irradiation (TBI) was investigated by means of the spleen colony assay. 5-FU was given intraperitoneally in doses ranging from 75 to 225 mg/kg body weight. TBI was administrated as a single fraction in the dose range 0.75-3.50 Gy. The frequency of stem cells declined rapidly and reached a minimum (nadir) on day 1-2 after either of the 2 treatments. Their number returned to near-pretreatment values by day 7-10. Increasing the dose of either 5-FU or TBI resulted in a lower nadir in stem cell survival and a higher regeneration rate of the stem cells. The maximal regeneration rate corresponded to a doubling time of 19 h. The time to complete regeneration was constant and neither influenced by the treatment modality nor by the dose. Both this work and previous studies on cyclophosphamide and combined 5-FU and TBI may indicate that the regeneration rate of bone marrow stem cells after a cytotoxic assault is influenced primarily by the stem cell surviving the treatment rather than the treatment modality.