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Analysis of the stem cell sparing properties of cyclophosphamide
Author(s) -
Gardner Renee V.,
McKin E.,
Astle C. M.
Publication year - 2001
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1034/j.1600-0609.2001.067001014.x
Subject(s) - cyclophosphamide , haematopoiesis , stem cell , pharmacology , hematopoietic stem cell , medicine , chemistry , andrology , immunology , chemotherapy , biology , genetics
Objectives: Cyclophosphamide was examined for its ability to spare the most primitive hematopoietic stem cell (PHSC). Methods: C57BL6/J mice (Groups A and B) were sacrificed 24 h and 4–6 wk, respectively, after a single or second injection of low‐dose cyclophos‐phamide (90 mg/kg) on days 1, 3, 7, or 15. A competitive repopulation assay was then performed, using B6‐ Hbb d Gpi‐1 a competitor cells, to determine the repopulating ability of exposed PHSC. Results and Conclusions: PHSC function was preserved after a single injection of cyclophosphamide and after a second injection on days 7 and 15 in both groups. In Group A, PHSC repopulating ability declined after a second injection on days 1 and 3 ( p <0.05 only for day 1), as did repopulating units [RU]; PHSC numbers did not. In Group B, an insignificant decrease in repopulating ability and RU numbers was observed after a second injection on days 1 and 3, suggesting different etiologies for losses in the 2 groups, or correction of drug‐induced defects within 1 month of cyclophosphamide administration. Total RU increased in single, day 1, 7 and 15 treatment groups. A significant number of marrow cells entered the S phase after cyclophosphamide dosing on day 3, and it is possible that a relationship exists between cell cycling and replicative damage. DNA damage was also increased 1 and 3 d after cyclophosphamide administration, although the significance of differences from controls was not definitive. Conclusion: Low‐dose cyclophosphamide can spare stem cells, depending upon the timing of subsequent doses.