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
Jazyk: angličtina
Rok vydání: 2020
Předmět:
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
Externí odkaz: