Patterns of recovery of high proliferation potential colony-forming cells after stressing the haemopoietic system--I.

The rates at which the number of high proliferation potential colony-forming cells and other haemopoietic cells recovered after different first stresses and a standard second stress were studied. The following first stresses were compared; different doses of sublethal irradiation (2.57, 4.84 and 5.5 Gy) followed by endogenous repopulation; lethal irradiation followed by exogenous repopulation; lethal irradiation of radio-protected mice followed by endogenous repopulation; and treatment with busulphan. Six to 16 weeks after these first stresses a standard second stress was applied. This was i.v. injection of fluorouracil. Two, four and six days later the number of high proliferation potential colony-forming cells in femora was determined and recovery curves for these cells were calculated. Their number increased exponentially in this period in all mice studied except radio-protected, lethally irradiated ones. In these, the exponential increase occurred between four and eight days after fluorouracil. The rate of increase was faster than normal in sublethally irradiated and radio-protected, lethally irradiated animals whose haemopoietic systems repopulated endogenously; in lethally irradiated, exogenously reconstituted animals it was the same as normal and in busulphan-treated animals it was slower than normal. The marrow from these differently stressed mice was also cultured with seven doses of two synergistic factors to contrast the growth of high proliferation potential colony-forming cells in the mice whose first stresses had differed. The cultures were assessed automatically by the CLIP 4 image processor. The high proliferation potential colony-forming cells of sublethally irradiated and busulphan-treated mice required more synergistic factor than normals to form a given number of cells/femur.