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

• Published in: Leukemia research Vol. 6; no. 6; pp. 815 - 818
• Main Authors: Hübner, Günter E., Cronkite, Eugene P.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 1982
• Subjects: 125iodo-deoxyuridine; Animals; busulfan and cyclophosphamide; Cell Division - drug effects; Female; Hematopoietic stem cells; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - metabolism; Idoxuridine - metabolism; intracellular residual damage; Iodine Radioisotopes; Male; methylnitrosourea; Methylnitrosourea - pharmacology; Mice; Mice, Inbred C57BL; 125 IUdR; BU; MNU; 125iodo-deoxyuridine; intracellular residual damage; busulfan and cyclophosphamide; methylnitrosourea; CP; Hematopoietic stem cells
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/0145-2126(82)90064-9

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.