scholarly journals DNA damage response in peripheral mouse blood leukocytesin vivoafter variable, low-dose rate exposure

2019 ◽  
Author(s):  
Qi Wang ◽  
Monica C. Pujol ◽  
Guy Garty ◽  
Maria Taveras ◽  
Jay Perrier ◽  
...  
Keyword(s):  
Dna Damage ◽  
Total Dose ◽  
Dose Rate ◽  
Dna Damage Response ◽  
Low Dose ◽  
Reactor Accident ◽  
Roc Curve Analysis ◽  
Low Dose Rate ◽  
Damage Response ◽  
Accumulated Dose

AbstractEnvironmental contamination and ingestion of the radionuclide Cesium-137 (137Cs) is a large concern in fallout from a nuclear reactor accident and 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 External137Cs irradiatoR (VADER), which can provide arbitrarily varying and progressive low dose rate irradiations in the range of 1.2 to 0.1 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 rate137Cs 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 signal protein p53 and DNA repair biomarker γ-H2AX were measured. The results illustrated that blood leukocyte count had significantly dropped by days 7. P53 levels peaked at day 2 (total dose=0.91Gy) and then declined whereas γ-H2AX yields generally increased with accumulated dose and peaked at day 5 (total dose=2.08Gy). ROC curve analysis for γ-H2AX provided a good discrimination of accumulated dose < 2 Gy and ≥ 2 Gy, highlighting the potential of γ-H2AX as a biomarker dosimetry in a protracted, environmental exposure scenario.

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

2020 ◽  
Vol 59 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Qi Wang ◽  
Monica Pujol-Canadell ◽  
Maria Taveras ◽  
Guy Garty ◽  
Jay Perrier ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dose Rate ◽  
Dna Damage Response ◽  
Low Dose ◽  
Mouse Blood ◽  
Blood Leukocytes ◽  
Low Dose Rate ◽  
Damage Response

scholarly journals Differential DNA Damage Response of Peripheral Blood Lymphocyte Populations

2021 ◽  
Vol 12 ◽  
Author(s):  
Kerstin Felgentreff ◽  
Catharina Schuetz ◽  
Ulrich Baumann ◽  
Christian Klemann ◽  
Dorothee Viemann ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Ionizing Radiation ◽  
Dna Damage Response ◽  
Peripheral Blood ◽  
Low Dose ◽  
Lymphocyte Subsets ◽  
Mass Cytometry ◽  
Damage Response ◽  
Lymphocyte Populations

DNA damage occurs constantly in every cell triggered by endogenous processes of replication and metabolism, and external influences such as ionizing radiation and intercalating chemicals. Large sets of proteins are involved in sensing, stabilizing and repairing this damage including control of cell cycle and proliferation. Some of these factors are phosphorylated upon activation and can be used as biomarkers of DNA damage response (DDR) by flow and mass cytometry. Differential survival rates of lymphocyte subsets in response to DNA damage are well established, characterizing NK cells as most resistant and B cells as most sensitive to DNA damage. We investigated DDR to low dose gamma radiation (2Gy) in peripheral blood lymphocytes of 26 healthy donors and 3 patients with ataxia telangiectasia (AT) using mass cytometry. γH2AX, p-CHK2, p-ATM and p53 were analyzed as specific DDR biomarkers for functional readouts of DNA repair efficiency in combination with cell cycle and T, B and NK cell populations characterized by 20 surface markers. We identified significant differences in DDR among lymphocyte populations in healthy individuals. Whereas CD56+CD16+ NK cells showed a strong γH2AX response to low dose ionizing radiation, a reduced response rate could be observed in CD19+CD20+ B cells that was associated with reduced survival. Interestingly, γH2AX induction level correlated inversely with ATM-dependent p-CHK2 and p53 responses. Differential DDR could be further noticed in naïve compared to memory T and B cell subsets, characterized by reduced γH2AX, but increased p53 induction in naïve T cells. In contrast, DDR was abrogated in all lymphocyte populations of AT patients. Our results demonstrate differential DDR capacities in lymphocyte subsets that depend on maturation and correlate inversely with DNA damage-related survival. Importantly, DDR analysis of peripheral blood cells for diagnostic purposes should be stratified to lymphocyte subsets.

Investigation of Low Dose Rate and Bias Conditions on the Total Dose Tolerance of a CMOS Flash-Based FPGA

2012 ◽  
Vol 59 (1) ◽  
pp. 134-143 ◽  
Author(s):  
Sana Rezgui ◽  
Edward P. Wilcox ◽  
Poongyeub Lee ◽  
Martin A. Carts ◽  
Kenneth LaBel ◽  
...  
Keyword(s):  
Total Dose ◽  
Dose Rate ◽  
Low Dose ◽  
Low Dose Rate ◽  
Dose Tolerance

Analysis of bipolar linear circuit response mechanisms for high and low dose rate total dose irradiations

1996 ◽  
Vol 43 (6) ◽  
pp. 3040-3048 ◽  
Author(s):  
H. Barnaby ◽  
H.J. Tausch ◽  
R. Turfler ◽  
P. Cole ◽  
P. Baker ◽  
...  
Keyword(s):  
Total Dose ◽  
Dose Rate ◽  
Low Dose ◽  
Linear Circuit ◽  
Low Dose Rate
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