Kinetics of Stem Cell Depletion and Proliferation: Effects of Vinblastine and Vincristine in Normal and Irradiated Mice

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Abstract
Vinblastine (VLB) caused a depression followed by an overcorrection in colony-forming units (CFU) of mice, as assayed by transplantation of spleen and marrow cells into irradiated recipients. Two days after VLB injection the femur showed a greater loss in nucleated cells than in CFU, resulting in a threefold increase in CFU concentration. The fraction of CFU recovered from the recipient spleen was 0.08 in these mice, compared to 0.20 for controls. On the basis of this lower transplantation fraction, the concentration of colony-forming cells in the femur is estimated to be 2/100 nucleated cells. Mice irradiated 2 days after an injection of VLB or vincristine showed a marked increase in endogenous splenic colonies and an early proliferative recovery of CFU. With VLB and 400 rads, exponential growth of femoral CFU began immediately, with no dip or lag phase apparent. This could not be attributed to an increased number of CFU at the time of irradiation or to a decreased radiation sensitivity. The effect was not seen in untreated mice given 200 rads, where the survival fraction was 7 times that for 400 rads. The CFU recovery pattern in mice pretreated with VLB appears therefore to result from a qualitative effect on the cells, which promotes early resumption of cell division after irradiation.