Comparison of the Sensitivity of Normal Hematopoietic and Transplanted Lymphoma Colony-Forming Cells to Chemotherapeutic Agents Administered In Vivo2

Abstract
The effects of 10 anticancer agents on the proliferative capacity of normal hematopoietic and lymphoma colony-forming cells were measured and compared. These agents included nitrogen mustard, tritiated thymidine, vinblastine, amethopterin, azaserine, 5-fluorouracil, actinomycin D, cyclophosphamide, 6-mercaptopurine, and hydrocortisone. The cells were obtained from the femoral marrows of mice 24 hours after administration of the drugs. Three classes of response were observed. With nitrogen mustard, survival curves were approximately exponential, and as found earlier with γ-radiation, the sensitivities of normal and lymphoma cells to this agent were similar. For tritiated thymidine, vinblastine, amethopterin, and azaserine, the sensitivities of the two cell types were different: The survival decreased as a function of dose to constant values. These levels were similar for all four agents, but differed markedly between normal and lymphoma cells. The constant values were approximately 20% of the control for normal hematopoietic cells and about 0.05% of control for lymphoma cells. A third class of compounds including 5-fluorouracil, actinomycin D, and cyclophosphamide yielded survival curves exponential throughout the dose range examined. The slopes for lymphoma cells were sixfold to tenfold greater than those for the normal cells. The response of the two cell types to 6-mercaptopurine and hydrocortisone was limited and could not be classified. The data are discussed in relation to the action of the agents on proliferating and nonproliferating cells, and to the fact that few, if any, of the normal hematopoietic colony-forming cells in marrow are in the generation cycle, whereas most lymphoma cells are in the generation cycle.