Amifostine plus granulocyte colony-stimulating factor therapy enhances recovery from supralethal radiation exposures: preclinical experience in animals models.
A murine model was used to explore whether the cytoprotective agent amifostine (WR-2721) can be used to protect a critical fraction of haemopoietic stem cells against radiation, and whether granulocyte colony-stimulating factor (G-CSF) can then be used to stimulate the protected cells to proliferate and reconstitute the haematopoietic system. Groups of C3H/HeN mice treated with 200 mg/kg amifostine i.p. 30 min before 60Co irradiation and/or 125 micrograms/kg G-CSF subcutaneously from days 1-16 post irradiation were compared. The dose reduction factor (DRF) of the combination of amifostine and G-CSF from LD50/30 values was greater than the sum of the DRFs for amifostine and G-CSF individually. Acceleration of recovery bone marrow and splenic multipotent stem cells (CFU-s) and granulocyte-macrophage progenitor cells (GM-CFC), as well as of peripheral blood red and white cells and platelets, was greatest in mice treated with amifostine plus G-CSF. These studies suggest that amifostine and recombinant haematopoietic growth factors can be used in combination to reduce myelosuppression and lethality associated with radiation or radiomimetic drugs
Patchen
M L
ML
Alpha Beta Technologies, Worcester, Massachusetts 01605, USA.
D004999:Amifostine / Q000627:therapeutic use*; D000818:Animals; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects*; D007928:Lethal Dose 50; D051379:Mice; D008809:Mice, Inbred C3H; D011833:Radiation Injuries, Experimental / Q000517:prevention & control / Q000628:therapy*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use
D011837:Radiation-Protective Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D004999:Amifostine