Drug-induced residual damage of murine hematopoietic stem cells measured by a new assay.

A recently developed assay for the measurement of residual stem cell damage after gamma-irradiation was tested to see if it could detect residual drug-induced stem cell damage. In this assay, the proliferative ability of transfused donor bone marrow is determined in the spleens of lethally irradiated recipients by the incremental increase of 125iodo-deoxyuridine (125IUdR) incorporation from day 3 to day 5. Three drugs were used to treat the donor: methylnitrosourea (MNU) 50 mg/kg; busulfan (BU) 20 mg/kg; cyclophosphamide (CP) 200 mg/kg. Residual damage of stem cells was detected 3 weeks after treatment in all mice. The measurable damage induced by MNU disappeared within 9 weeks, while damage caused by BU and CP was still present after 9 and 15 weeks. It is concluded that the new assay is suitable for the detection of proliferative defects in the stem cells induced by at least three alkylating agents.