Combined modality radioprotection: the use of glucan and selenium with WR-2721.
Glucan, WR-2721, and selenium, three agents with distinct radioprotective mechanisms, were evaluated in C3H/HeN mice for survival-enhancing and hemopoietic-regenerating effects when administered alone or in combinations before exposure to 60Co radiation. At LD50/30 radiation doses (radiation doses lethal for 50% of mice within 30 days postexposure), dose reduction factors of 1.21, 1.02, 1.37, 1.51, and 1.66 were obtained following glucan (75 mg/kg i.v., -20 hr), selenium (0.8 mg/kg, i.p., -20 hr), WR-2721 (200 mg/kg, i.p., -30 min), glucan + WR-2721, and glucan + selenium + WR-2721 treatments, respectively. All treatments increased numbers of hemopoietic stem cells as measured by the day 12 endogenous spleen colony-forming unit (E-CFU) assay; the most significant E-CFU effects, however, were observed following glucan + WR-2721 and glucan + selenium + WR-2721 treatments. Combined modality treatments were also more effective than single-agent treatments at accelerating bone marrow and splenic granulocyte-macrophage colony-forming cell (GM-CFC) regeneration. These results demonstrate the value of multiple-agent radioprotectants.
Patchen
M L
ML
Armed Forces Radiobiology Research Institute, Bethesda, MD 20814-5145.
MacVittie
T J
TJ
Weiss
J F
JF
D004999:Amifostine / Q000008:administration & dosage*; D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D004357:Drug Synergism; D005260:Female; D005936:Glucans / Q000008:administration & dosage*; D006410:Hematopoiesis / Q000528:radiation effects; D051379:Mice; D008809:Mice, Inbred C3H; D009946:Organothiophosphorus Compounds / Q000008:administration & dosage*; D011833:Radiation Injuries, Experimental / Q000401:mortality / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D012643:Selenium / Q000008:administration & dosage*; D013154:Spleen / Q000528:radiation effects
D005936:Glucans; D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; D012643:Selenium; D004999:Amifostine