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Survival of Hematopoietic and Lymphoma Colony-forming Cells in Vivo following the Administration of a Variety of Alkylating Agents¹

Mallinckrodt Institute of Radiology, Division of Radiation Therapy, Section of Cancer Biology, Washington University School of Medicine, St. Louis, Missouri 63110

Dose-survival curves for murine hematopoietic stem cells and transplanted syngeneic lymphoma cells were constructed for a variety of alkylating agents administered in vivo. A comparison of the slopes of the dose-survival curves, defined as the efficacy ratio, provided a quantitative measure of the differential sensitivity of these two cell populations to a given alkylating agent. Nitrogen mustard yielded no differential killing of the malignant cell population when compared with thy normal, while cyclophosphamide, the most efficacious agent examined, was extremely selective for the lymphoma cells. The efficacy of the other agents tested fell between these two extremes. In increasing order of efficacy were nitrogen mustard, tris(1-aziridinyl)phosphine sulfide, phenylalanine mustard, triethylenemelamine, chlorambucil, NSC 82196, 1,3-bis(2-chloroethyl)-1-nitrosourea, and cyclophosphamide. While the mechanism for the difference in selectivity of cell lethality observed among the different alkylating agents is not known, a possible explanation is presented, together with its implications.

¹ Supported by USPHS Grant CA-10435 from the National Cancer Institute, NIH.

Received 9/22/71. Accepted 11/18/71.