title: The Gottingen minipig is a model of the hematopoietic acute radiation syndrome: G-colony stimulating factor stimulates hematopoiesis and enhances survival from lethal total-body γ-irradiation.
abstract: OBJECTIVE
  We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis.
  
  
  METHODS
  Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation.
  
  
  RESULTS
  The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages.
  
  
  CONCLUSIONS
  These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes.
authors.affiliation: Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA. maria.moroni@usuhs.edu
authors.forename: Maria
authors.initials: M
authors.lastname: Moroni
authors.forename: Barbara F
authors.initials: BF
authors.lastname: Ngudiankama
authors.forename: Christine
authors.initials: C
authors.lastname: Christensen
authors.forename: Cara H
authors.initials: CH
authors.lastname: Olsen
authors.forename: Rossitsa
authors.initials: R
authors.lastname: Owens
authors.forename: Eric D
authors.initials: ED
authors.lastname: Lombardini
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Holt
authors.forename: Mark H
authors.initials: MH
authors.lastname: Whitnall
mesh_terms: D054508:Acute Radiation Syndrome / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D000818:Animals; D002097:C-Reactive Protein / Q000032:analysis; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006410:Hematopoiesis / Q000187:drug effects* / Q000528:radiation effects; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009503:Neutropenia / Q000188:drug therapy; D058958:Organs at Risk / Q000528:radiation effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D015203:Reproducibility of Results; D013552:Swine; D013556:Swine, Miniature; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D002097:C-Reactive Protein; D000069585:Filgrastim