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 γ-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.
Highlights
Humans are increasingly exposed to ionizing radiation (IR) through routine clinical therapeutic procedures and radiological accidents [1,2,3]
We evaluate the suitability of the minipig model for γ-H2AX-based radiation biodosimetry by first examining lymphocytes and fibroblasts from minipigs exposed ex vivo to ionizing radiation as well as lymphocytes from pigs exposed to total body irradiation from a Co60 source
The nearly identical responses observed between human and minipig lymphocytes suggests that the minipig may be a good model for developing a γ-H2AX-based radiation biodosimeter to study human radiation exposure
Summary
Humans are increasingly exposed to ionizing radiation (IR) through routine clinical therapeutic procedures and radiological accidents [1,2,3]. Long-term effects of radiation exposure include major health issues ranging from fibrosis to cancer [1,6,7]. Appropriate clinical treatments such as general medical management (barrier nursing conditions, administration of antibiotic, antimycotic and antiviral substances), administration of cytokines for bone marrow stimulation (i.e., G-CSF), growth factors, antioxidants as well as stem cell therapy [8], could mitigate some of these effects. The Gottingen minipig or miniature swine [18], is currently being developed as a model to study and treat the effect of ionizing radiation in humans [12,14,19]. A review on the use of swine in radiological research can be found elsewhere [20]
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