This study was purposed to evaluate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on hematopoietic reconstruction and survival in beagles exposed to mixed fission neutron and γ-ray. 13 beagles were unilaterally exposed to single dose of 2.3 Gy 90% neutrons. The experiments were divided into 3 groups: irradiation control group (no any treatment, n = 4), supportive care group (n = 5) and rhG-CSF plus supportive care group (n = 4, abbreviated as rhG-CSF group) in which the beagles were subcutaneously injected with 200 µg/kg of rhG-CSF early at half an hour and 24 hours post-irradiation respectively. The results showed that 2.3 Gy 90% neutron irradiation induced a severe acute radiation sickness of bone marrow type. The administration of rhG-CSF increased the survival rate from 60% in supportive care group to 100%. Twice injection of rhG-CSF in the first 24 hours reduced duration of neutropenia, enhanced neutrophil nadir and promoted neutrophil recovery when compared with control cohort administered clinical support. The number of colony-forming cells (CFU-GM, CFU-E, and BFU-E) in peripheral blood of rhG-CSF treated canines increased 2-to 5-fold relative to those of the supportive care group on day 3. All canines treated with rhG-CSF achieved hematopoietic reconstruction as evidenced by the pathological section of sternum while severe shortage of hemopoietic cells remained in the cohorts given supportive care alone. It is concluded that the combination of supportive care and high-dose rhG-CSF can accelerate hematopoietic recovery and enhance survival of dogs exposed to 2.3 Gy mixed neutron and gamma ray.
Animals ; Dogs ; Gamma Rays ; adverse effects ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; pharmacology ; Hematopoietic System ; drug effects ; radiation effects ; Neutron Diffraction ; Recombinant Proteins ; administration & dosage ; pharmacology ; Survival Rate

The aim of this study was to investigate the effect of recombinant human granulocyte stimulating factor (rhG-CSF) on blood coagulation of beagles irradiated by 2.3 Gy neutron so as to provide new therapy for blood coagulation disorder after neutron irradiation. 10 beagles were exposed to 2.3 Gy neutron, and then randomly assigned into supportive care group and rhG-CSF-treated group. The rhG-CSF-treated cohorts were injected subcutaneously with rhG-CSF (10 µg/kg·d) beginning at the day of exposure for 21 consecutive days. Peripheral blood platelet counts were examined once every two days. In vitro platelet aggregation test, thromboelastography and blood clotting tetrachoric tests were also performed. The results indicated that the blood clotting system of irradiated dogs was in hypercoagulable state in the early days after 2.3 Gy neutron irradiation, and became hypocoagulable at crisis later and were mainly on intrinsic coagulation pathway. Blood fibrinogen increased markedly during the course of disease, while platelet counts and aggregation function were decreased remarkably. rhG-CSF administered daily could correct hypercoagulable state induced by 2.3 Gy neutron irradiation at the early time post exposure, shortened the thromboplastin generation time and clotting formation, down-regulated the abnormal high fibrinogen in blood, and improved platelet aggregation function. It is concluded that rhG-CSF can improve coagulation disorders of irradiated dogs.
Animals ; Blood Coagulation ; drug effects ; Bone Marrow ; radiation effects ; Dogs ; Granulocyte Colony-Stimulating Factor ; pharmacology ; therapeutic use ; Humans ; Leukocyte Count ; Neutron Diffraction ; Platelet Count ; Radiation Dosage ; Radiation Injuries, Experimental ; physiopathology ; Recombinant Proteins