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

Technical Report · Mon Jan 01 00:00:00 EST 1990

OSTI ID:6262661

Macvittie, T J; Monroy, R L; Patchen, M L; Souza, L M

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
• Resource Relation: Other Information: Pub. in International Jnl. of Radiation Biology, Vol. 57, No. 4, 723-736(1990)
• Country of Publication: United States
• Language: English

Related Subjects

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