In vivo protective effects of tetrapeptide AcSDKP, with or without granulocyte colony-stimulation factor, on murine progenitor cells after sublethal irradiation.
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 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 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 hypothesis and protocols.
Watanabe
T
T
Department of Pathology, University of Nebraska Medical Center, Omaha 68198-5660, USA.
Brown
G S
GS
Kelsey
L S
LS
Yan
Y
Y
Jackson
J D
JD
Ewel
C
C
Kessinger
A
A
Talmadge
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005720:Gamma Rays; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D015918:Infusion Pumps, Implantable; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000008:administration & dosage* / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*
D009842:Oligopeptides; D011837:Radiation-Protective Agents; D016179:Granulocyte Colony-Stimulating Factor; C058504:goralatide