Effects of recombinant transforming growth factor-β1 on hematologic recovery after treatment of mice with 5-fluorouracil

Rob Jansen, Giovanna Damia, Noriko Usui, Jonathan Keller, Hitoyasu Futami, Hoo Goey, Timothy T. Back, Dan L. Longo, Francis W. Ruscetti, Robert H. Wiltrout

Research output: Contribution to journalArticle

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Abstract

Transforming growth factor β1 (TGF-β1) has been shown to inhibit bone marrow colony formation after in vitro treatment as well as after in vivo administration to normal mice. These data suggest that TGF-β might either protect, or further depress, progenitor cell levels in mice exposed to a cell cycle-active drug such as 5-fluorouracil (5FU). rTGF-β1 was administered repeatedly by either the i.v. or i.p. routes to mice during the hyperproliferative state of the bone marrow that occurs 7 to 9 days after the i.v. administration of 150 mg/kg 5FU. The formation of both multilineage and the more differentiated (CFU-c) colonies was inhibited by 20 to 40%/culture, and 66 to 93%/mouse. When multiple doses of rTGF-β1 were administered systemically immediately before the injection of 5FU, the resulting rebound in the number of CFU-c and multilineage colonies containing granulocyte, erythroid, megakaryocyte, and macrophage lineage colonies per culture was markedly inhibited by 30 to 77%, whereas the total number of CFU per mouse was inhibited up to 93%. This effect was maximal when rTGF-β1 was administered at daily doses of ≥5 μg/mouse for at least 3 days. This inhibition of the recovery of the bone marrow from 5FU treatment induced by rTGF-β1 was a delayed transient response because by day 16 the progenitor cell numbers and bone marrow cellularity were identical to the 5FU-treated marrow controls.

Original languageEnglish
Pages (from-to)3342-3347
Number of pages6
JournalJournal of Immunology
Volume147
Issue number10
Publication statusPublished - Nov 15 1991

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Transforming Growth Factors
Fluorouracil
Bone Marrow
Stem Cells
Therapeutics
Megakaryocytes
Granulocytes
Cell Cycle
Cell Count
Macrophages
Injections
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Immunology

Cite this

Jansen, R., Damia, G., Usui, N., Keller, J., Futami, H., Goey, H., ... Wiltrout, R. H. (1991). Effects of recombinant transforming growth factor-β1 on hematologic recovery after treatment of mice with 5-fluorouracil. Journal of Immunology, 147(10), 3342-3347.

Effects of recombinant transforming growth factor-β1 on hematologic recovery after treatment of mice with 5-fluorouracil. / Jansen, Rob; Damia, Giovanna; Usui, Noriko; Keller, Jonathan; Futami, Hitoyasu; Goey, Hoo; Back, Timothy T.; Longo, Dan L.; Ruscetti, Francis W.; Wiltrout, Robert H.

In: Journal of Immunology, Vol. 147, No. 10, 15.11.1991, p. 3342-3347.

Research output: Contribution to journalArticle

Jansen, R, Damia, G, Usui, N, Keller, J, Futami, H, Goey, H, Back, TT, Longo, DL, Ruscetti, FW & Wiltrout, RH 1991, 'Effects of recombinant transforming growth factor-β1 on hematologic recovery after treatment of mice with 5-fluorouracil', Journal of Immunology, vol. 147, no. 10, pp. 3342-3347.
Jansen, Rob ; Damia, Giovanna ; Usui, Noriko ; Keller, Jonathan ; Futami, Hitoyasu ; Goey, Hoo ; Back, Timothy T. ; Longo, Dan L. ; Ruscetti, Francis W. ; Wiltrout, Robert H. / Effects of recombinant transforming growth factor-β1 on hematologic recovery after treatment of mice with 5-fluorouracil. In: Journal of Immunology. 1991 ; Vol. 147, No. 10. pp. 3342-3347.
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