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Evaluation of the Gamma-H2AX Assay for Radiation Biodosimetry in a Swine Model
Armed Forces Radiobiology Research Institute, Uniformed Services University, Bethesda, MD 20889-5603, USA
Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 25 May 2013; in revised form: 18 June 2013 / Accepted: 25 June 2013 / Published: 8 July 2013
Abstract: There is a paucity of large animal models to study both the extent and the health risk of ionizing radiation exposure in humans. One promising candidate for such a model is the minipig. Here, we evaluate the minipig for its potential in γ-H2AX-based biodosimetry after exposure to ionizing radiation using both Cs137 and Co60 sources. γ-H2AX foci were enumerated in blood lymphocytes and normal fibroblasts of human and porcine origin after ex vivo g-ray irradiation. DNA double-strand break repair kinetics in minipig blood lymphocytes and fibroblasts, based on the γ-H2AX assay, were similar to those observed in their human counterparts. To substantiate the similarity observed between the human and minipig we show that minipig fibroblast radiosensitivity was similar to that observed with human fibroblasts. Finally, a strong γ-H2AX induction was observed in blood lymphocytes following minipig total body irradiation. Significant responses were detected 3 days after 1.8 Gy and 1 week after 3.8 and 5 Gy with residual γ-H2AX foci proportional to the initial radiation doses. These findings show that the Gottingen minipig provides a useful in vivo model for validation of γ-H2AX biodosimetry for dose assessment in humans.
Keywords: Gottingen minipig; immunocytofluorescence-based γ-H2AX; ionizing radiation; lymphocytes; fibroblasts
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Moroni, M.; Maeda, D.; Whitnall, M.H.; Bonner, W.M.; Redon, C.E. Evaluation of the Gamma-H2AX Assay for Radiation Biodosimetry in a Swine Model. Int. J. Mol. Sci. 2013, 14, 14119-14135.
Moroni M, Maeda D, Whitnall MH, Bonner WM, Redon CE. Evaluation of the Gamma-H2AX Assay for Radiation Biodosimetry in a Swine Model. International Journal of Molecular Sciences. 2013; 14(7):14119-14135.
Moroni, Maria; Maeda, Daisuke; Whitnall, Mark H.; Bonner, William M.; Redon, Christophe E. 2013. "Evaluation of the Gamma-H2AX Assay for Radiation Biodosimetry in a Swine Model." Int. J. Mol. Sci. 14, no. 7: 14119-14135.