The organization of hemopoietic tissue as inferred from the effects of 5-fluorouracil

Abstract

Mouse bone marrow obtained one day after injection of 5-fluorouracil (FU) had a markedly diminished content of spleen colony forming units (CFUs) but retained its capacity to repopulate the marrow granulocyte-macrophage colony forming cell (GM-CFC) and CFUs compartments of 850 R irradiated hosts and had only a slightly reduced platelet repopulating ability (PRA). A significant correlation (r = 0.94, P less than 0.001) was observed between the content of high proliferative potential granulocyte-macrophage progenitor (HPP-GM-CFC) and the platelet and marrow GM-CFC repopulating abilities of bone marrow cell suspensions. Spleens of irradiated mice, injected with marrow from donors treated with FU between 1 and 7 days before showed an increase in colony numbers with time of sampling between 8-13 days after transplantation. In contrast, the colony counts observed in mice injected with normal bone marrow remained constant over that time interval. The colonies derived from bone marrow of FU treated mice grew faster than those from bone marrow of normal mice. Spleens obtained from irradiated mice, 10 days after injection of bone marrow derived from donors treated with FU 1 or 3 days before, showed only a few macroscopic surface colonies but when sectioned were found to contain large numbers of microscopic colonies, 80% of which were megakaryocytic. The results are interpreted on the basis of a clonal succession model of hemopoiesis with stem cells of varying proliferative potential and proliferation rates increasing as capacity for cell production decreases.