DNA damage response in peripheral mouse blood leukocytes in vivo after variable, low-dose rate exposure
Autor: | Maria Taveras, Carlos Bueno-Beti, Jay R. Perrier, David J. Brenner, Guy Garty, Qi Wang, Monica Pujol-Canadell, Helen Turner, Igor Shuryak |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Male
DNA Repair DNA repair DNA damage Biophysics Apoptosis Radiation Dosage Article 030218 nuclear medicine & medical imaging Andrology Histones 03 medical and health sciences Leukocyte Count Mice 0302 clinical medicine Biodosimetry In vivo Leukocytes Ingestion Animals General Environmental Science Radiation Chemistry Environmental exposure Mice Inbred C57BL Cesium Radioisotopes 030220 oncology & carcinogenesis Biomarker (medicine) Tumor Suppressor Protein p53 Biomarkers DNA Damage |
Zdroj: | Radiat Environ Biophys |
ISSN: | 1432-2099 |
Popis: | Environmental contamination and ingestion of the radionuclide Cesium-137 ((137)Cs) 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 (137)Cs irradiatoR (VADER), which can provide arbitrarily varying and progressive low dose rate irradiations in the range of 0.1 to 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 (137)Cs 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 leukocytes depletion, apoptosis as well as its signal protein p53 and DNA repair biomarker γ-H2AX were 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 dosimetry in a protracted, environmental exposure scenario. |
Databáze: | OpenAIRE |
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