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Therapeutic use of recombinant human G-CSF (RHG-CSF) in a canine model of sublethal and lethal whole-body irradiation

Technical Report ·
OSTI ID:6262661
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The short biologic half-life of the peripheral neutrophil (PMN) requires an active granulopoietic response to replenish functional PMSs and to remain a competent host defence in irradiated animals. Recombinant human G-CSF (rhG-CSF) was studied for its ability to modulate hemopoiesis in normal dogs as well as to decrease therapeutically the severity and duration of neutropenia in sublethally and lethally irradiated dogs. For the normal dog, subcutaneous administration of rhG-CSF induced neutrophilia within hours after the first injection; total PMSs continued to increase (with plateau phases) to mean peak values of 1000 per cent of baseline at the end of the treatment period (12-14 days). Bone-marrow-derived granulocyte-macrophage colony-forming cells (GM-CFC) increased significantly during treatment. For a sublethal 200 cGy dose, treatment with rhG-CSF for 14 consecutive days decreased the severity and shortened the duration of neutropenia and thrombocytopenia. The radiation-induced lethality of 60 per cent after a dose of 350 cGy was associated with marrow-derived GM-CFC survival of 1 per cent.

Research Organization:
Armed Forces Radiobiology Research Inst., Bethesda, MD (USA)
OSTI ID:
6262661
Report Number(s):
AD-A-227555/0/XAB; AFRRI-SR--90-15
Country of Publication:
United States
Language:
English

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Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL HALF-LIFE
BIOLOGICAL MATERIALS
BIOLOGICAL MODELS
BLOOD
BLOOD CELLS
BODY FLUIDS
DOGS
EXTERNAL IRRADIATION
GROWTH FACTORS
IRRADIATION
LETHAL IRRADIATION
LEUKOCYTES
MAMMALS
MAN
MATERIALS
MITOGENS
NEUTROPHILS
ORGANIC COMPOUNDS
PRIMATES
PROTEINS
RADIOSENSITIVITY EFFECTS
SUBLETHAL IRRADIATION
VERTEBRATES
WHOLE-BODY IRRADIATION