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

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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
Issue number10
Publication statusPublished - Nov 15 1991

ASJC Scopus subject areas

  • Immunology

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