TY - JOUR
T1 - The gottingen minipig is a model of the hematopoietic acute radiation syndrome
T2 - G-colony stimulating factor stimulates hematopoiesis and enhances survival from lethal total-body γ-irradiation
AU - Moroni, Maria
AU - Ngudiankama, Barbara F.
AU - Christensen, Christine
AU - Olsen, Cara H.
AU - Owens, Rossitsa
AU - Lombardini, Eric D.
AU - Holt, Rebecca K.
AU - Whitnall, Mark H.
N1 - Funding Information:
Supported by funding from National Institute of Allergy and Infectious Diseases Y1-AI-1759-01 and Armed Forces Radiobiology Research Institute (AFRRI) RBB2DG . The opinions or assertions contained herein are the private views of the authors and are not necessarily those of AFRRI, the Uniformed Services University of the Health Sciences, or the Department of Defense. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
PY - 2013/8/1
Y1 - 2013/8/1
N2 - Purpose: 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 and Materials: 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.
AB - Purpose: 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 and Materials: 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.
UR - http://www.scopus.com/inward/record.url?scp=84879999764&partnerID=8YFLogxK
U2 - 10.1016/j.ijrobp.2013.04.041
DO - 10.1016/j.ijrobp.2013.04.041
M3 - Article
C2 - 23845847
AN - SCOPUS:84879999764
SN - 0360-3016
VL - 86
SP - 986
EP - 992
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 5
ER -