Dataset Information

Evaluation of the gamma-H2AX assay for radiation biodosimetry in a swine model.

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 ?-H2AX-based biodosimetry after exposure to ionizing radiation using both Cs137 and Co60 sources. ?-H2AX foci were enumerated in blood lymphocytes and normal fibroblasts of human and porcine origin after ex vivo ?-ray irradiation. DNA double-strand break repair kinetics in minipig blood lymphocytes and fibroblasts, based on the ?-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 ?-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 ?-H2AX foci proportional to the initial radiation doses. These findings show that the Gottingen minipig provides a useful in vivo model for validation of ?-H2AX biodosimetry for dose assessment in humans.

SUBMITTER: Moroni M

PROVIDER: S-EPMC3742235 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Evaluation of the gamma-H2AX assay for radiation biodosimetry in a swine model.

Moroni Maria M Maeda Daisuke D Whitnall Mark H MH Bonner William M WM Redon Christophe E CE

International journal of molecular sciences 20130708 7

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 k ...[more]

PMID: 23880859

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Project description:Inhalation and ingestion of 137Cs and other long-lived radionuclides can occur after large-scale accidental or malicious radioactive contamination incidents, resulting in a complex temporal pattern of radiation dose/dose rate, influenced by radionuclide pharmacokinetics and chemical properties. High-throughput radiation biodosimetry techniques for such internal exposure are needed to assess potential risks of short-term toxicity and delayed effects (e.g., carcinogenesis) for exposed individuals. Previously, we used γ-H2AX to reconstruct injected 137Cs activity in experimentally-exposed mice, and converted activity values into radiation doses based on time since injection and 137Cs-elimination kinetics. In the current study, we sought to assess the feasibility and possible advantages of combining γ-H2AX with transcriptomics to improve 137Cs activity reconstructions. We selected five genes (Atf5, Hist2h2aa2, Olfr358, Psrc1, Hist2h2ac) with strong statistically-significant Spearman's correlations with injected activity and stable expression over time after 137Cs injection. The geometric mean of log-transformed signals of these five genes, combined with γ-H2AX fluorescence, were used as predictors in a nonlinear model for reconstructing injected 137Cs activity. The coefficient of determination (R2) comparing actual and reconstructed activities was 0.91 and root mean squared error (RMSE) was 0.95 MBq. These metrics remained stable when the model was fitted to a randomly-selected half of the data and tested on the other half, repeated 100 times. Model performance was significantly better when compared to our previous analysis using γ-H2AX alone, and when compared to an analysis where genes are used without γ-H2AX, suggesting that integrating γ-H2AX with gene expression provides an important advantage. Our findings show a proof of principle that integration of radiation-responsive biomarkers from different fields is promising for radiation biodosimetry of internal emitters.

Dataset Information

Evaluation of the gamma-H2AX assay for radiation biodosimetry in a swine model.

Publications

Evaluation of the gamma-H2AX assay for radiation biodosimetry in a swine model.

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