Long-term effects of high doses of cytosine arabinoside on pluripotent stem cells (CFU-S).
The purpose of this work was to investigate the long-term effects of high doses of cytosine arabinoside (Ara-C) on the pluripotent stem cell (spleen colony-forming units; CFU-S) compartment in mice. Studies were carried out on mice that survived the administration of repeated high doses of Ara-C (HDAra-C) with or without the injection of a partially purified CFU-S inhibitor or a bone marrow graft. The following features were examined 1, 1.5, and 5-7 months after treatment: CFU-S number, proliferative ability, and differentiation into different lineages. The results indicate that these parameters, which were severely disturbed soon after drug administration, returned to control levels within a month and remained unchanged as compared to age-matched controls for the following 6 months. Therefore, HDAra-C, given alone or with a CFU-S inhibitor or prior to bone marrow grafting, did not seem to induce long-lasting damage of the CFU-S compartment. However, our studies cannot eliminate the possibility of some residual stromal damage or some impairment of other properties of stem cells. It would be of importance to further clarify these points because HDAra-C are now used in the treatment of leukemias and prior to bone marrow transplantation.
Guigon
M
M
INSERM U250, Institut Gustave-Roussy, Villejuif, France.
Izumi-Hisha
H
H
Mary
J Y
JY
D000818:Animals; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003561:Cytarabine / Q000008:administration & dosage / Q000633:toxicity*; D004334:Drug Administration Schedule; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D013154:Spleen / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors
D003561:Cytarabine