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Influence of Timing of Administration of 5-Fluorouracil to Donors on Bone Marrow Engraftment in Nonmyeloablated Hosts

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Abstract

We evaluated the engraftment and the cell cycle status of marrow cells at various times after 5-fluorouracil (5-FU) administration. 5-FU (150 mg/kg) was given to donor male BALB/c mice at 1, 2, 6, or 12 days prior to marrow harvest. The donor cells were then assessed in host nonmyeloablated female mice. Bone marrow engraftment of marrow treated with 5-FU was evaluated and compared to marrow treated with diluent (phosphate-buffered saline) at 3 and 10 weeks after marrow infusion. Our data show a rapid induction of an engraftment defect 1 day after 5-FU, persistence of this defect through day 6, and a recovery by day 12. Experiments using hydroxyurea (which selectively kills cells in the S phase) to determine the cell cycle status indicated that cells that engrafted in post-5-FU marrow were noncycling at days 1, 2, and 12 but cycling at day 6. Post-5-FU bone marrow was also analyzed in vitro by colony assays and its cycling status determined by3H-thymidine suicide assay. High-proliferative-potential colony-forming cells (HPP-CFCs) and low-proliferative-potential colony-forming cells (LPP-CFCs) decreased rapidly 1 day after 5-FU, with a nadir observed at day 6 for HPP-CFCs and day 2 for LPP-CFCs. By day 12, LPP-CFCs showed a total recovery, but HPP-CFCs were still defective. Significant numbers of HPP-CFCs were cycling, mostly at days 6 and 8 after 5-FU, whereas LPP-CFCs appeared quiescent except at day 2. These results emphasize the importance of timing if post-5-FU marrow is used for gene therapy or marrow transplantation.

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Authors and Affiliations

  1. Centre Hospitalier Notre-Dame et Reine Fabiola, Charleroi, Belgium

    Lionel D’Hondt

  2. Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Lionel D’Hondt, Jane Carlson, Brian Benoit, Judith Reilly, Christina Grimaldi, Joanne Wuu, Jean-François Lambert, Mark S. Dooner & Peter J. Quesenberry

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  1. Lionel D’Hondt
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  2. Jane Carlson
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  3. Brian Benoit
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  4. Judith Reilly
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  5. Christina Grimaldi
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  6. Joanne Wuu
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  7. Jean-François Lambert
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  8. Mark S. Dooner
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  9. Peter J. Quesenberry
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Correspondence to Lionel D’Hondt.

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D’Hondt, L., Carlson, J., Benoit, B. et al. Influence of Timing of Administration of 5-Fluorouracil to Donors on Bone Marrow Engraftment in Nonmyeloablated Hosts. Int J Hematol 74, 79–85 (2001). https://doi.org/10.1007/BF02982554

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  • DOI: https://doi.org/10.1007/BF02982554

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