scholarly journals A theoretical cell-killing model to evaluate oxygen enhancement ratios at DNA damage and cell survival endpoints in radiation therapy

2020 ◽  
Vol 65 (9) ◽  
pp. 095006
Author(s):  
Yusuke Matsuya ◽  
Tatsuhiko Sato ◽  
Rui Nakamura ◽  
Shingo Naijo ◽  
Hiroyuki Date
Keyword(s):  
Dna Damage ◽  
Radiation Therapy ◽  
Cell Survival ◽  
Cell Killing ◽  
Survival Endpoints ◽  
Oxygen Enhancement

Oxygen enhancement ratios of cancer cells after exposure to intensity modulated x-ray fields: DNA damage and cell survival

2021 ◽  
Author(s):  
Yusuke Matsuya ◽  
Stephen J McMahon ◽  
Karl T Butterworth ◽  
Shingo Naijo ◽  
Isshi Nara ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Survival ◽  
Cancer Cells ◽  
X Ray ◽  
Intensity Modulated ◽  
Oxygen Enhancement

scholarly journals A Mathematical Radiobiological Model (MRM) to Predict Complex DNA Damage and Cell Survival for Ionizing Particle Radiations of Varying Quality

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 840
Author(s):  
Spyridon A. Kalospyros ◽  
Zacharenia Nikitaki ◽  
Ioanna Kyriakou ◽  
Michael Kokkoris ◽  
Dimitris Emfietzoglou ◽  
...  
Keyword(s):  
Dna Damage ◽  
Radiation Therapy ◽  
Cell Survival ◽  
Radiation Protection ◽  
Multiscale Approach ◽  
Cross Sectional ◽  
Beam Radiation ◽  
Biological Damage ◽  
Radiobiological Model ◽  
Radiobiological Effects

Predicting radiobiological effects is important in different areas of basic or clinical applications using ionizing radiation (IR); for example, towards optimizing radiation protection or radiation therapy protocols. In this case, we utilized as a basis the ‘MultiScale Approach (MSA)’ model and developed an integrated mathematical radiobiological model (MRM) with several modifications and improvements. Based on this new adaptation of the MSA model, we have predicted cell-specific levels of initial complex DNA damage and cell survival for irradiation with 11Β, 12C, 14Ν, 16Ο, 20Νe, 40Αr, 28Si and 56Fe ions by using only three input parameters (particle’s LET and two cell-specific parameters: the cross sectional area of each cell nucleus and its genome size). The model-predicted survival curves are in good agreement with the experimental ones. The particle Relative Biological Effectiveness (RBE) and Oxygen Enhancement Ratio (OER) are also calculated in a very satisfactory way. The proposed integrated MRM model (within current limitations) can be a useful tool for the assessment of radiation biological damage for ions used in hadron-beam radiation therapy or radiation protection purposes.

scholarly journals Characterisation of deubiquitylating enzymes in the cellular response to high-LET ionising radiation and complex DNA damage

2018 ◽  
Author(s):  
Rachel J. Carter ◽  
Catherine M. Nickson ◽  
James M. Thompson ◽  
Andrzej Kacperek ◽  
Mark A. Hill ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Survival ◽  
Cellular Response ◽  
Cell Killing ◽  
Dna Lesions ◽  
Ionising Radiation ◽  
X Rays ◽  
High Let Radiation ◽  
High Let ◽  
Parp 1

AbstractPurposeIonising radiation, particular high linear energy transfer (LET) radiation, can induce complex DNA damage (CDD) where two or more DNA lesions are induced in close proximity which contributes significantly to the cell killing effects. However knowledge of the enzymes and mechanisms involved in co-ordinating the recognition and processing of CDD in cellular DNA are currently lacking.Methods and MaterialsAn siRNA screen of deubiquitylation enzymes was conducted in HeLa cells irradiated with high-LET -particles or protons, versus low-LET protons and x-rays, and cell survival monitored by clonogenic assays. Candidates whose depletion led to decreased cell survival specifically in response to high-LET radiation were validated in both HeLa and oropharyngeal squamous cell carcinoma (UMSCC74A) cells, and the association with CDD repair was confirmed by using an enzyme modified neutral comet assay.ResultsDepletion of USP6 decreased cell survival specifically following high-LET α-particles and protons, but not by low-LET protons or x-rays. USP6 depletion caused cell cycle arrest and a deficiency in CDD repair mediated through instability of poly(ADP-ribose) polymerase-1 (PARP-1). This phenotype was mimicked using the PARP inhibitor olaparib.ConclusionUSP6 controls cell survival in response to high-LET radiation by stabilising PARP-1 protein levels which is essential for CDD repair. We also describe synergy between CDD induced by high-LET protons and PARP inhibition in effective cancer cell killing.

scholarly journals A Role for Histone H2B During Repair of UV-Induced DNA Damage in Saccharomyces cerevisiae

Genetics ◽  
2002 ◽  
Vol 160 (4) ◽  
pp. 1375-1387
Author(s):  
Emmanuelle M D Martini ◽  
Scott Keeney ◽  
Mary Ann Osley
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Chromatin Structure ◽  
Specific Effect ◽  
Cell Killing ◽  
Cyclobutane Pyrimidine Dimers ◽  
Histone H2b ◽  
Uv Sensitivity ◽  
Pyrimidine Dimers

Abstract To investigate the role of the nucleosome during repair of DNA damage in yeast, we screened for histone H2B mutants that were sensitive to UV irradiation. We have isolated a new mutant, htb1-3, that shows preferential sensitivity to UV-C. There is no detectable difference in bulk chromatin structure or in the number of UV-induced cis-syn cyclobutane pyrimidine dimers (CPD) between HTB1 and htb1-3 strains. These results suggest a specific effect of this histone H2B mutation in UV-induced DNA repair processes rather than a global effect on chromatin structure. We analyzed the UV sensitivity of double mutants that contained the htb1-3 mutation and mutations in genes from each of the three epistasis groups of RAD genes. The htb1-3 mutation enhanced UV-induced cell killing in rad1Δ and rad52Δ mutants but not in rad6Δ or rad18Δ mutants, which are defective in postreplicational DNA repair (PRR). When combined with other mutations that affect PRR, the histone mutation increased the UV sensitivity of strains with defects in either the error-prone (rev1Δ) or error-free (rad30Δ) branches of PRR, but did not enhance the UV sensitivity of a strain with a rad5Δ mutation. When combined with a ubc13Δ mutation, which is also epistatic with rad5Δ, the htb1-3 mutation enhanced UV-induced cell killing. These results suggest that histone H2B acts in a novel RAD5-dependent branch of PRR.

scholarly journals Temporal regulation of the Mus81-Mms4 endonuclease ensures cell survival under conditions of DNA damage

2013 ◽  
Vol 41 (19) ◽  
pp. 8943-8958 ◽  
Author(s):  
Irene Saugar ◽  
María Victoria Vázquez ◽  
María Gallo-Fernández ◽  
María Ángeles Ortiz-Bazán ◽  
Mónica Segurado ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Survival ◽  
Temporal Regulation

scholarly journals Gold Nanoparticles Radio-sensitize and Reduce Cell Survival in Lewis Lung Carcinoma

2020 ◽  
Author(s):  
Arvind Pandey ◽  
Veronica Vighetto ◽  
Nicola Di Marzio ◽  
Matteo Hirsch ◽  
Nicola Ferrante ◽  
...  
Keyword(s):  
Dna Damage ◽  
Particle Size ◽  
Gold Nanoparticles ◽  
Cell Survival ◽  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Lewis Lung ◽  
Lung Carcinoma Cells ◽  
Reduce Cell Survival

It has been suggested that particle size plays an important role in determining the genotoxicity of gold nanoparticles (GNPs). The purpose of this study was to compare the potential radio-sensitization effects of two different sized GNPs (3.9 and 37.4 nm) fabricated and examined in vitro in Lewis Lung carcinoma (LLC) as a model of non-small cell lung cancer through use of comet and clonogenic assays. After the treatment of 2Gy X-ray irradiation, both particle sizes demonstrated increased DNA damage when compared to treatment with particles only and radiation alone. This radio-sensitization was further translated into a reduction in cell survival demonstrated by clonogenicity. This work indicates that GNPs of both sizes induce DNA damage in LLC cells at the tested concentrations, whereas the 37.4 nm particle size treatment group demonstrated greater significance in vitro. The presented data aids in the evaluation of the radiobiological response of Lewis Lung carcinoma cells treated with gold nanoparticles.

Cellular damage in vitro

2009 ◽  
Vol 48 (05) ◽  
pp. 208-214 ◽  
Author(s):  
J. Drechsel ◽  
R. Freudenberg ◽  
R. Runge ◽  
G. Wunderlich ◽  
J. Kotzerke ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Survival ◽  
Cell Line ◽  
Cellular Damage ◽  
Thyroid Cell ◽  
Response Curves ◽  
Beta Emitters ◽  
Thyroid Cell Line ◽  
Clonogenic Cell ◽  
Radionuclide Uptake

Summary Aim: The cellular damage of ionising radiation depends on dose, physical radiation quality (e. g. LET) and intracellular radionuclide uptake. The influence of two beta emitters (188Re and 131I) on the thyroid cell line PC Cl3 was studied. Furthermore, we analysed the effect of intracellular accumulation. Methods: The thyroid cell line PC Cl3 was irradiated with 188Re-perrhenate or 131I-sodium iodide in presence or absence of perchlorate. The initial DNA-damage was measured in the comet assay as olive tail moment (OTM). The colony forming assay detects the clonogenic cell survival as surviving fraction. Additional the intracellular radionuclide uptake was quantified. Results: Dose response curves were established for irradiation with 188Re-perrhenate or 131I-iodine under various extra- and intracellular activity distribution conditions. In the presence of perchlorate DNA-damage and clonogenic cell survival for both radionuclides were comparable. In the absence of perchlorat radionuclide uptake of 1.39% (131I) and 4.14% (188Re) were measured causing twofold higher radiotoxicity. Although 131I uptake was lower than 188Re uptake the OTM values were higher und surviving fractions were lower. Conclusions: 131I, compared to 188Re, has lower mean beta energy and a higher LET, and therefore, it induced a higher DNA-damage even at lower intracellular uptake. An additional explanation for the higher radiotoxicity of 131I could be the higher dose exposition caused by crossfire through neighborhood cells.

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