Granulocyte colony-stimulating factor and amifostine (Ethyol) synergize to enhance hemopoietic reconstitution and increase survival in irradiated animals.
The reported studies tested whether amifostine could be used to protect hemopoietic stem cells, which, after irradiation, could be stimulated by granulocyte colony-stimulating factor (G-CSF) to proliferate and reconstitute the hemopoietic system. Female C3H/HeN mice were administered amifostine (Ethyol, US Bioscience, Inc, West Conshohocken, PA) (200 mg/kg intraperitoneally 30 minutes before cobalt-60 irradiation and G-CSF (125 micrograms/kg/d subcutaneously from days 1 to 16 after irradiation. Saline, G-CSF, amifostine, and amifostine plus G-CSF treatments resulted in LD50/30 values of 7.85 Gy, 8.30 Gy, 11.30 Gy, and 12.85 Gy, respectively. At these LD50/30 values, the dose reduction factor of 1.64 obtained in combination-treated mice was more than additive between the dose reduction factors of G-CSF-treated mice (1.06) and amifostine-treated mice (1.44). Bone marrow and splenic multipotent hemopoietic stem cell and granulocyte-macrophage progenitor cell recoveries, as well as peripheral white blood cell, platelet, and red blood cell recoveries were also accelerated most in mice treated with amifostine plus G-CSF. These studies demonstrate that therapeutically administered G-CSF accelerates hemopoietic reconstitution from amifostine-protected stem and progenitor cells, increasing the survival-enhancing effects of amifostine, and suggest that classic radioprotectants and recombinant hemopoietic growth factors can be used in combination to reduce the risks associated with myelosuppression induced by radiation or radiomimetic drugs.
Patchen
M L
ML
Department of Experimental Hematology, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5603.
MacVittie
T J
TJ
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004357:Drug Synergism; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000528:radiation effects; D051379:Mice; D008809:Mice, Inbred C3H; D011833:Radiation Injuries, Experimental / Q000276:immunology* / Q000517:prevention & control
D016179:Granulocyte Colony-Stimulating Factor; D004999:Amifostine