International Journal of Cell Cloning, Vol 8, 107-122, Copyright © 1990 by AlphaMed Press

ORIGINAL ARTICLES

Therapeutic administration of recombinant human granulocyte colony- stimulating factor accelerates hemopoietic regeneration and enhances survival in a murine model of radiation-induced myelosuppression

ML Patchen, TJ MacVittie, BD Solberg and LM Souza
Department of Experimental Hematology, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20814-5145.

The primary cause of death after radiation exposure is infection resulting from myelosuppression. Because granulocytes play a critical role in host defense against infection and because granulocyte proliferation and differentiation are enhanced by granulocyte colony- stimulating factor (G-CSF), this agent was evaluated for the ability to accelerate hemopoietic regeneration and to enhance survival in irradiated mice. C3H/HeN mice were irradiated and G-CSF (2.5 micrograms/day, s.c.) or saline was administered on days 3-12, 1-12 or 0-12 post-irradiation. Bone marrow, splenic and peripheral blood cellularity, and bone marrow and splenic granulocyte-macrophage progenitor cell recoveries were evaluated in mice exposed to 6.5 Gy. Mice exposed to 8 Gy were evaluated for multipotent hemopoietic stem cell recovery (using endogenous spleen colony-forming units) and enhanced survival. Results demonstrated that therapeutic G-CSF 1) accelerates hemopoietic regeneration after radiation-induced myelosuppression, 2) enhances survival after potentially lethal irradiation and 3) is most effective when initiated 1 h following exposure.

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