In vivo protective effects of tetrapeptide AcSDKP, with or without granulocyte colony-stimulating factor, on murine progenitor cells after sublethal irradiation

T. Watanabe, G. S. Brown, L. S. Kelsey, Y. Yan, J. D. Jackson, C. Ewel, A. Kessinger, J. E. Talmadge

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) demonstrated hemato-protective activity in mice after sublethal irradiation (7 Gy). Bone marrow interleukin-3 (IL-3)-responsive colony-forming cells (CFC) and high proliferative potential colony-forming cells (HPP-CFC) were significantly (P < 0.05) increased by day 10 after irradiation in mice receiving a continuous infusion of 1000 ng/day of AcSDKP compared to irradiated control mice. The maximum protective effect for bone marrow progenitors was achieved when AcSDKP was administered for 3 days beginning. 24 hours before irradiation. Other dosages and schedules in relationship to irradiation were less active. Further, when granulocyte colony-stimulating factor (G-CSF) was administered for 10 days after AcSDKP infusion in irradiated mice, significantly increased numbers of IL-3-responsive CFC and HPP-CFC in the bone marrow and spleen were observed 14-21 days after irradiation compared with G-CSF-only control mice. In addition, platelets were significantly (p < 0.05) increased in mice receiving AcSDKP and G-CSF on days 18 and 21 after irradiation compared with mice receiving G-CSF alone. We conclude that AcSDKP has a radioprotective effect in vivo for progenitor cells, and that time of initiation and duration of AcSDKP administration relative to irradiation are crucial for these effects. Further, AcSDKP has a significant additive protective effect not only for progenitor cells but also for platelets when given in combination with G-CSF. We suggest that these in vivo observations provide a basis on which to design optimal clinical hypotheses and protocols.

Original languageEnglish (US)
Pages (from-to)713-721
Number of pages9
JournalExperimental Hematology
Volume24
Issue number6
StatePublished - 1996

Keywords

  • AcSDKP
  • G-CSF
  • Progenitor cells
  • Radioprotective

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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