RhG-CSF improves radiation-induced myelosuppression and survival in the canine exposed to fission neutron irradiation.

Fission-neutron radiation damage is hard to treat due to its critical injuries to hematopoietic and gastrointestinal systems, and so far few data are available on the therapeutic measures for neutron-radiation syndrome. This study was designed to test the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in dogs which had received 2.3 Gy mixed fission-neutron-γ irradiation with a high ratio of neutrons (~90%). Following irradiation, rhG-CSF treatment induced 100% survival versus 60% in controls. Only two of five rhG-CSF-treated dogs experienced leukopenia (white blood cells [WBC] count < 1.0 × 10(9)/L) and neutropenia (neutrophil [ANC] count < 0.5 × 10(9)/L), whereas all irradiated controls displayed a profound period of leukopenia and neutropenia. Furthermore, administration of rhG-CSF significantly delayed the onset of leukopenia and reduced the duration of leucopenia as compared with controls. In addition, individual dogs in the rhG-CSF-treated group exhibited evident differences in rhG-CSF responsiveness after neutron-irradiation. Finally, histopathological evaluation of the surviving dogs revealed that the incidence and severity of bone marrow, thymus and spleen damage decreased in rhG-CSF-treated dogs as compared with surviving controls. Thus, these results demonstrated that rhG-CSF administration enhanced recovery of myelopoiesis and survival after neutron-irradiation.

[1]  Yu-wen Cong,et al.  [Effect of rhG-CSF on blood coagulation in beagles irradiated by 2.3 Gy neutron]. , 2010, Zhongguo shi yan xue ye xue za zhi.

[2]  J. Leitner,et al.  Single dose granulocyte colony-stimulating factor markedly enhances shear-dependent platelet function in humans , 2010, Platelets.

[3]  M. Esaki,et al.  Recombinant human granulocyte colony-stimulating factor reduces colonic epithelial cell apoptosis and ameliorates murine dextran sulfate sodium-induced colitis , 2008, Scandinavian journal of gastroenterology.

[4]  工藤 哲司 Recombinant human granulocyte colony-stimulating factor reduces colonic epithelial cell apoptosis and ameliorates murine dextran sulfate sodium-induced colitis , 2008 .

[5]  B. Yeğen,et al.  Granulocyte colony stimulating factor ameliorates radiation-induced morphological destruction of intestinal mucosa in rats , 2008 .

[6]  R. Haziroğlu,et al.  Protective effects of recombinant human granulocyte colony stimulating factor in a rat model of necrotizing enterocolitis , 2006, Pediatric Surgery International.

[7]  A. Farese,et al.  DEFINING THE FULL THERAPEUTIC POTENTIAL OF RECOMBINANT GROWTH FACTORS IN THE POST RADIATION-ACCIDENT ENVIRONMENT: THE EFFECT OF SUPPORTIVE CARE PLUS ADMINISTRATION OF G-CSF , 2005, Health physics.

[8]  Y. Buechler,et al.  Effects of Recombinant Human Interleukin 11 on Thrombocytopenia and Neutropenia in Irradiated Rhesus Monkeys , 2004, Radiation research.

[9]  James Armitage,et al.  Medical Management of the Acute Radiation Syndrome: Recommendations of the Strategic National Stockpile Radiation Working Group , 2004, Annals of Internal Medicine.

[10]  P. Topçuoğlu,et al.  Administration of granulocyte-colony-stimulating factor for allogeneic hematopoietic cell collection may induce the tissue factor-dependent pathway in healthy donors , 2004, Bone Marrow Transplantation.

[11]  T. Asahara,et al.  Regulation of T helper type-1 immunity in hapten-induced colitis by host pretreatment with granulocyte colony-stimulating factor. , 2003, Cytokine.

[12]  C. Demers,et al.  A prospective study of G-CSF effects on hemostasis in allogeneic blood stem cell donors , 1999, Bone Marrow Transplantation.

[13]  M Marchetti,et al.  Neutrophil activation and hemostatic changes in healthy donors receiving granulocyte colony-stimulating factor. , 1999, Blood.

[14]  A. Tichelli,et al.  Indicators of haematopoietic recovery after bone marrow transplantation: the role of reticulocyte measurements. , 1996, Clinical and laboratory haematology.

[15]  C. Baum,et al.  Combination therapy for radiation-induced bone marrow aplasia in nonhuman primates using synthokine SC-55494 and recombinant human granulocyte colony-stimulating factor. , 1996, Blood.

[16]  A. Farese,et al.  Therapeutic efficacy of recombinant human leukemia inhibitory factor in a primate model of radiation-induced marrow aplasia. , 1994, Blood.

[17]  A. Farese,et al.  Therapeutic efficacy of recombinant interleukin-6 (IL-6) alone and combined with recombinant human IL-3 in a nonhuman primate model of high-dose, sublethal radiation-induced marrow aplasia. , 1994, Blood.

[18]  D. Williams,et al.  Combination protocols of cytokine therapy with interleukin-3 and granulocyte-macrophage colony-stimulating factor in a primate model of radiation-induced marrow aplasia. , 1993, Blood.

[19]  A. Bigas,et al.  A single dose of granulocyte colony-stimulating factor modifies radiation-induced death in B6D2F1 mice. , 1993, Experimental hematology.

[20]  Baoqin Wang,et al.  The Response of Dogs to Mixed Neutron-γ Radiation with Different n/γ Ratios@@@The Response of Dogs to Mixed Neutron-g Radiation with Different n/g Ratios , 1991 .

[21]  G. Zeman,et al.  The relative biological effectiveness of mixed fission-neutron-gamma radiation on the hematopoietic syndrome in the canine: effect of therapy on survival. , 1991, Radiation research.

[22]  N. Nara,et al.  Effects of recombinant human granulocyte colony-stimulating factor on the hematologic recovery and survival of irradiated mice. , 1990, Blood.

[23]  T. MacVittie,et al.  Therapeutic use of recombinant human G-CSF (rhG-CSF) in a canine model of sublethal and lethal whole-body irradiation. , 1990, International journal of radiation biology.

[24]  R Storb,et al.  Effect of recombinant human granulocyte colony-stimulating factor on hematopoiesis of normal dogs and on hematopoietic recovery after otherwise lethal total body irradiation. , 1989, Blood.

[25]  J. J. Broerse,et al.  Mortality of monkeys after exposure to fission neutrons and the effect of autologous bone marrow transplantation. , 1978, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[26]  J. Davids Bone-marrow syndrome in CBA mice exposed to fast neutrons of 1.0 MeV mean energy. Effect of syngeneic bone-marrow transplantation. , 1970, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[27]  E. J. Ainsworth,et al.  Comparative lethality responses of neutron- and x-irradiated dogs: influence of dose rate and exposure aspect. , 1965, Radiation research.

[28]  E. Alpen,et al.  The effects of total-body irradiation of dogs with simulated fission neutrons. , 1960, Radiation research.

[29]  S. J. Baum,et al.  Autologous bone-marrow implantation after fast neutron irradiation of dogs. , 1959, Radiation research.

[30]  M. L. Randolph,et al.  Effect of bone marrow treatment on mortality of mice irradiated with fast neutrons. , 1957, Science.