In vivo radioprotective effect of AcSDKP on canine myelopoiesis.
The tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) interferes with G1/S-phase progression, and the resulting cell cycle arrest is thought to protect hematopoietic stem cells against injury by cycle-active cytotoxic agents. We investigated the radioprotective effect of AcSDKP in a canine radiation model. Dogs were given total-body irradiation (TBI) at an exposure rate of 10 cGy/min, either without further therapy (control) or with administration of AcSDKP at 0.05-500 micrograms/ kg/24 h beginning before and continuing until after completion of TBI. At 400 cGy of TBI, one of 28 control dogs and one of eight AcSDKP-treated dogs recovered hematopoiesis (p = 0.40). At 300 cGy, seven of 21 control dogs recovered hematopoiesis compared with five of five AcSDKP-treated dogs (p = 0.01). In dogs given 300 cGy and AcSDKP, the granulocyte nadirs were less profound (p = 0.04) and occurred later (p = 0.04) than among controls; platelet kinetics did not differ. These data suggest, therefore, that AcSDKP provides a radioprotective effect in dogs exposed to 300 cGy TBI. Such an effect might be beneficial in recipients of intensive radiation therapy. Conceivably, the effect on hematopoietic recovery could be amplified by growth factor administration after irradiation.
Deeg
H J
HJ
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98104-2092, USA.
Seidel
K
K
Hong
D S
DS
Yu
C
C
Huss
R
R
Schuening
F G
FG
Ewel
C H
CH
Storb
R
R
D000818:Animals; D001853:Bone Marrow / Q000254:growth & development* / Q000502:physiology*; D004285:Dogs; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010976:Platelet Count / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014916:Whole-Body Irradiation
D009842:Oligopeptides; D011837:Radiation-Protective Agents; C058504:goralatide