Engraftment of post 5-fluorouracil murine marrow into minimally myeloablated (100 cGy) murine hosts.
Minimal myeloablative approaches are now being widely applied in the treatment of different hematological malignancies. One hundred cGy whole-body irradiation is a stem-cell-toxic, relatively non-myelotoxic treatment that allows for relatively high levels of donor chimerism. 5-Fluorouracil (5-FU) treatment leads to a relative concentration of high proliferative potential-colony-forming cell (HPP-CFC) and is an approach that has been used to induce in vivo progenitor/stem cell cycling to facilitate retroviral integration in gene therapy approaches. We have now evaluated the capacity of marrow harvested 1, 2, 6, or 12 days after 5-FU treatment (150 mg/kg) to engraft in 100 cGy-treated female BALB/c mice. Engraftment was assessed at 3, 10, and 24 weeks. A rapid induction of an engraftment defect occurred 1 day post 5-FU and persisted through day 6 with a recovery by day 12. To evaluate cell cycle status of normal and 5-FU-treated marrow cells, male donors received hydroxyurea (900 mg/kg i.v.) or phosphate-buffered saline (PBS), 2 h prior to marrow harvest and transplantation into submyeloablated female recipients. Engraftment levels were similar for hydroxyurea-treated mice and controls. Thus, these studies show transiently defective engraftment of 5-FU-treated marrow into submyeloablated hosts, which may be related to the cell cycle status of the stem cells.
Centre Hospitalier Notre-Dame et Reine Fabiola, Charleroi, Belgium.
Lionel
L
D'Hondt
Jean-François
JF
Lambert
Jeffrey
J
Damon
Brian O
BO
Benoit
Jan
J
Cerny
Jane E
JE
Carlson
Judy
J
Reilly
Joanne
J
Wuu
Gerald A
GA
Colvin
Mark S
MS
Dooner
Peter J
PJ
Quesenberry
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D016026:Bone Marrow Transplantation / Q000379:methods*; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D011829:Radiation Dosage; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods; D014916:Whole-Body Irradiation / Q000379:methods*
D005472:Fluorouracil