DIFFERENT RECOVERY PATTERNS OF MOUSE HEMATOPOIETIC STEM-CELLS IN RESPONSE TO CYTOTOXIC AGENTS

The response and subsequent recovery of mouse hemopoietic progenitor cells (spleen colony forming cells and agar colony forming cells) was studied following 2 cytotoxic antitumor agents. Busulfan was administered to normal mice and vinblastine to mice where the progenitor cell proliferation rate was increased by a continuous .gamma.-irradiation. With both agents there is a difference between the response of spleen colony forming cells and agar colony forming cells during the first 5 days. They recover together, but more slowly after busulfan than vinblastine, even though their proliferation rate is increased. The rate of progenitor cell recovery after busulfan is increased if the progenitor cells are depleted further by vinblastine. Methotrexate, which severly depletes the peripheral blood count and bone marrow cellularity but not the pregenitor cells, has no effect on recovery following busulfan. Following cytotoxic agents agar colony forming cells committed stem cells are not self-maintaining but are dependent on a supply of cells from the pluripotential spleen colony forming cells. It also appears that depletion of the progenitor cells of the bone marrow and not depletion of maturing cells, provides a stimulus for stem cell recovery.