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DNA damage response in peripheral mouse blood leukocytes in vivo after variable, low-dose rate exposure

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Abstract

Environmental contamination and ingestion of the radionuclide Cesium-137 (137Cs) is a large concern in fallout from a nuclear reactor accident or improvised nuclear device, and highlights the need to develop biological assays for low-dose rate, internal emitter radiation. To mimic low-dose rates attributable to fallout, we have developed a VAriable Dose-rate External 137Cs irradiatoR (VADER), which can provide arbitrarily varying and progressive low-dose rate irradiations in the range of 0.1–1.2 Gy/day, while circumventing the complexities of dealing with radioactively contaminated biomaterials. We investigated the kinetics of mouse peripheral leukocytes DNA damage response in vivo after variable, low-dose rate 137Cs exposure. C57BL/6 mice were placed in the VADER over 7 days with total accumulated dose up to 2.7 Gy. Peripheral blood response including the leukocyte depletion, apoptosis as well as its signal protein p53 and DNA repair biomarker γ-H2AX was measured. The results illustrated that blood leukocyte numbers had significantly dropped by day 7. P53 levels peaked at day 2 (total dose = 0.91 Gy) and then declined; whereas, γ-H2AX fluorescence intensity (MFI) and foci number generally increased with accumulated dose and peaked at day 5 (total dose = 2.08 Gy). ROC curve analysis for γ-H2AX provided a good discrimination of accumulated dose < 2 Gy and ≥ 2 Gy, highlighting the potential of γ-H2AX MFI as a biomarker for dosimetry in a protracted, environmental exposure scenario.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank Bezalel A. Bacon for sample measurement. We are also grateful to Matthew A. Rodrigues for valuable discussion of this work.

Funding

This work was supported by the Center for High-Throughput Minimally-Invasive Radiation Biodosimetry, National Institute of Allergy and Infectious Diseases (Grant number U19AI067773).

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Authors and Affiliations

  1. Center for Radiological Research, Columbia University Irving Medical Center, New York, NY, 10032, USA

    Qi Wang, Monica Pujol-Canadell, Maria Taveras, Guy Garty, Jay Perrier, Carlos Bueno-Beti, Igor Shuryak, David J. Brenner & Helen C. Turner

Authors
  1. Qi Wang
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  2. Monica Pujol-Canadell
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  3. Maria Taveras
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  4. Guy Garty
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  5. Jay Perrier
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  7. Igor Shuryak
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  8. David J. Brenner
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  9. Helen C. Turner
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Correspondence to Qi Wang.

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The authors declare that they have no competing interests.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards Columbia University Institutional Animal Care and Use Committee (IACUC, #AC-AAAQ2410).

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Wang, Q., Pujol-Canadell, M., Taveras, M. et al. DNA damage response in peripheral mouse blood leukocytes in vivo after variable, low-dose rate exposure. Radiat Environ Biophys 59, 89–98 (2020). https://doi.org/10.1007/s00411-019-00825-x

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