Effect of Cyclophosphamide on the Murine Hematopoietic Stem Cell Compartment as Measured by Different Assay Techniques

Three different methods have been used to measure the survival of the hematopoietic stem cell pool following treatment with cyclophosphamide. Two of these systems measure the stem cell pool by its ability to proliferate and differentiate into mature progeny. In both these methods irradiated recipient mice receive syngeneic bone marrow from either normal or cyclophosphamide-treated animals. A period of time is allowed for the transplanted progenitor cells to divide and differentiate, and then the progeny produced are assayed. Ability to form red blood cells is assessed by the amount of radioactive iron incorporated into newly formed erythrocytes. Capacity for granulocyte formation is measured by peripheral white blood cell counts following endotoxin stimulation. The pool as measured by its ability to produce erythrocytic progeny appears to be more sensitive than as measured by its ability to produce granulocytic progeny. The spleen colony assay gives results similar to the assay of granulocytic progeny. These results, taken with previous data indicating decrease in erythroid precursors in spleen colonies derived from cells surviving cyclophosphamide, are interpreted as indicating a decrease in ability for erythroid differentiation in cells surviving cyclophosphamide.