Survival enhancement and hemopoietic regeneration following radiation exposure: therapeutic approach using glucan and granulocyte colony-stimulating factor.
C3H/HeN female mice were exposed to wholebody cobalt-60 radiation and administered soluble glucan (5 mg i.v. at 1 h following exposure), recombinant human granulocyte colony-stimulating factor (G-CSF; 2.5 micrograms/day s.c., days 3-12 following exposure), or both agents. Treatments were evaluated for their ability to enhance hemopoietic regeneration, and to increase survival after radiation-induced myelosuppression. Both glucan and G-CSF enhanced hemopoietic regeneration alone; however, greater effects were observed in mice receiving both agents. For example, on day 17 following a sublethal 6.5-Gy radiation exposure, mice treated with saline, G-CSF, glucan, or both agents, respectively, exhibited 36%, 65%, 50%, and 78% of normal bone marrow cellularity, and 84%, 175%, 152%, and 212% of normal splenic cellularity. At this same time, granulocyte-macrophage colony-forming cell (GM-CFC) values in saline, G-CSF, glucan, or combination-treated mice, respectively, were 9%, 46%, 26%, and 57% of normal bone marrow values, and 57%, 937%, 364%, and 1477% of normal splenic values. Endogenous spleen colony formation was also increased in all treatment groups, with combination-treated mice exhibiting the greatest effects. Likewise, although both glucan and G-CSF alone enhanced survival following an 8-Gy radiation exposure, greatest survival was observed in mice treated with both agents. These studies suggest that glucan, a macrophage activator, can synergize with G-CSF to further accelerate hemopoietic regeneration and increase survival following radiation-induced myelosuppression.
Department of Experimental Hematology, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20814-5145.
M L
ML
Patchen
T J
TJ
MacVittie
B D
BD
Solberg
L M
LM
Souza
D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects*; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D005936:Glucans / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D051379:Mice; D008809:Mice, Inbred C3H; D012038:Regeneration / Q000187:drug effects; D013534:Survival; D014916:Whole-Body Irradiation
D003115:Colony-Stimulating Factors; D005936:Glucans; D016179:Granulocyte Colony-Stimulating Factor