The Comparative Effects Of Selected Cytotoxic Agents On Transplanted Hematopoietic Cells

SUMMARY Hematopoietic colony-forming units (CFU) from syngeneic bone marrow were assayed in mice pretreated with busulfan (BU) and cyclophosphamide (CY). Cortisone did not affect the development of these transplanted hematopoietic cells, but the suppressive effects of several cytotoxic agents varied with time of drug administration and the dose level used. The suppressive effects of either methotrexate (MTX), 6-mercaptopurine (6-MP), or vincristine (VCR) were most marked when the drug was given 24 hr or more following marrow transplantation, suggesting that these compounds affected actively proliferating cells most profoundly. The suppressive effect of CY (tested up to 5 days after marrow transplantation) was primarily dose-related, suggesting that all phases of the cells' proliferative cycle were affected equally. In contrast, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) seemed to exert its most profound effect on cells in a lag or resting phase, since maximum inhibition of colony development occurred when the drug was given shortly after marrow transplantation.