Postirradiation glucan administration enhances the radioprotective effects of WR-2721.
Based on murine survival studies, endogenous hemopoietic spleen colony formation (E-CFU), and recovery of bone marrow and splenic granulocyte-macrophage colony-forming cells (GM-CFC), it was demonstrated that the postirradiation administration of glucan, an immunomodulator and hemopoietic stimulant, enhances the radioprotective effects of WR-2721. LD50/30 dose reduction factors for mice treated with WR-2721 (200 mg/kg approximately 30 min before irradiation), glucan (250 mg/kg approximately 1 h after irradiation), or both agents were 1.37, 1.08, and 1.52, respectively. Enhanced survival in mice treated with both agents appeared to be due in part to glucan's ability to accelerate hemopoietic regeneration from stem cells initially protected from radiation-induced lethality by WR-2721. Following a 10-Gy radiation exposure, E-CFU numbers in mice treated with saline, WR-2721, glucan, or both WR-2721 and glucan were 0.05 +/- 0.03, 6.70 +/- 1.05, 0.95 +/- 0.24, and 33.90 +/- 2.96, respectively. Similarly, bone marrow and splenic GM-CFC numbers were greater in mice treated with both WR-2721 and glucan than in mice treated with either agent alone. These results demonstrated at least additive radioprotective effects when mice were given WR-2721 prior to irradiation and glucan following irradiation. These effects appeared to depend on the sequential cell protection mediated by WR-2721 and hemopoietic repopulation mediated by glucan.
Patchen
M L
ML
Department of Experimental Hematology, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20814-5145.
MacVittie
T J
TJ
Jackson
W E
WE
D004999:Amifostine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D003114:Colony-Forming Units Assay; D004357:Drug Synergism; D005260:Female; D005936:Glucans / Q000008:administration & dosage / Q000627:therapeutic use*; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D009946:Organothiophosphorus Compounds / Q000627:therapeutic use*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D005936:Glucans; D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; D004999:Amifostine