Analysis of the stem cell sparing properties of cyclophosphamide.
OBJECTIVE
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 cyclophosphamide (90 mg/kg) on days 1, 3, 7, or 15. A competitive repopulation assay was then performed, using B6-HbbdGpi-1a competitor cells, to determine the repopulating ability of exposed PHSC.


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.


CONCLUSIONS
Low-dose cyclophosphamide can spare stem cells, depending upon the timing of subsequent doses.
Gardner
R V
RV
Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA. rgardn@lsuhsc.edu
McKinnon
E
E
Astle
C M
CM
D000818:Animals; D020296:Animals, Congenic; D016026:Bone Marrow Transplantation; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019457:Chromosome Breakage; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects; D004334:Drug Administration Schedule; D005819:Genetic Markers; D006085:Graft Survival; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D015162:Micronucleus Tests; D011828:Radiation Chimera
D005819:Genetic Markers; D003520:Cyclophosphamide