scholarly journals DNA damage in lens epithelial cells exposed to occupationally-relevant X-ray doses and role in cataract formation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ion Udroiu ◽  
Antonella Sgura ◽  
Agnese Chendi ◽  
Lorenzo Lasagni ◽  
Marco Bertolini ◽  
...  
Keyword(s):  
Dna Damage ◽  
Monte Carlo ◽  
Epithelial Cells ◽  
Lens Epithelial Cells ◽  
Eye Lens ◽  
Monte Carlo Code ◽  
Cataract Formation ◽  
X Ray ◽  
Radiation Induced ◽  
The Relationship

AbstractThe current framework of radiological protection of occupational exposed medical workers reduced the eye-lens equivalent dose limit from 150 to 20 mSv per year requiring an accurate dosimetric evaluation and an increase understanding of radiation induced effects on Lens cells considering the typical scenario of occupational exposed medical operators. Indeed, it is widely accepted that genomic damage of Lens epithelial cells (LEC) is a key mechanism of cataractogenesis. However, the relationship between apoptosis and cataractogenesis is still controversial. In this study biological and physical data are combined to improve the understanding of radiation induced effects on LEC. To characterize the occupational exposure of medical workers during angiographic procedures an INNOVA 4100 (General Electric Healthcare) equipment was used (scenario A). Additional experiments were conducted using a research tube (scenario B). For both scenarios, the frequencies of binucleated cells, micronuclei, p21-positive cells were assessed with different doses and dose rates. A Monte-Carlo study was conducted using a model for the photon generation with the X-ray tubes and with the Petri dishes considering the two different scenarios (A and B) to reproduce the experimental conditions and validate the irradiation setups to the cells. The simulation results have been tallied using the Monte Carlo code MCNP6. The spectral characteristics of the different X-ray beams have been estimated. All irradiated samples showed frequencies of micronuclei and p21-positive cells higher than the unirradiated controls. Differences in frequencies increased with the delivered dose measured with Gafchromic films XR-RV3. The spectrum incident on eye lens and Petri, as estimated with MCNP6, was in good agreement in the scenario A (confirming the experimental setup), while the mean energy spectrum was higher in the scenario B. Nevertheless, the response of LEC seemed mainly related to the measured absorbed dose. No effects on viability were detected. Our results support the hypothesis that apoptosis is not responsible for cataract induced by low doses of X-ray (i.e. 25 mGy) while the induction of transient p21 may interfere with the disassembly of the nuclear envelop in differentiating LEC, leading to cataract formation. Further studies are needed to better clarify the relationship we suggested between DNA damage, transient p21 induction and the inability of LEC enucleation.

Radiation-induced DNA Damage and Repair in Lens Epithelial Cells of both Ptch1(+/–) and Ercc2(+/–) Mutated Mice

2021 ◽  
Vol 197 (1) ◽  
Author(s):  
S. G. R. Barnard ◽  
R. McCarron ◽  
M. Mancuso ◽  
I. De Stefano ◽  
S. Pazzaglia ◽  
...  
Keyword(s):  
Dna Damage ◽  
Epithelial Cells ◽  
Lens Epithelial Cells ◽  
Dna Damage And Repair ◽  
Radiation Induced

KGF facilitates repair of radiation-induced DNA damage in alveolar epithelial cells

1997 ◽  
Vol 272 (6) ◽  
pp. L1174-L1180 ◽  
Author(s):  
M. Takeoka ◽  
W. F. Ward ◽  
H. Pollack ◽  
D. W. Kamp ◽  
R. J. Panos
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Epithelial Cells ◽  
Dna Polymerase ◽  
Dna Polymerases ◽  
Dna Strand Breaks ◽  
Strand Breaks ◽  
Alveolar Epithelial ◽  
Radiation Induced ◽  
Dna Strand

Administration of exogenous keratinocyte growth factor (KGF) prevents or attenuates several forms of oxidant-mediated lung injury. Because DNA damage in epithelial cells is a component of radiation pneumotoxicity, we determined whether KGF ameliorated DNA strand breaks in irradiated A549 cells. Cells were exposed to 137Cs gamma rays, and DNA damage was measured by alkaline unwinding and ethidium bromide fluorescence after a 30-min recovery period. Radiation induced a dose-dependent increase in DNA strand breaks. The percentage of double-stranded DNA after exposure to 30 Gy increased from 44.6 +/- 3.5% in untreated control cells to 61.6 +/- 5.0% in cells cultured with 100 ng/ml KGF for 24 h (P < 0.05). No reduction in DNA damage occurred when the cells were cultured with KGF but maintained at 0 degree C during and after irradiation. The sparing effect of KGF on radiation-induced DNA damage was blocked by aphidicolin, an inhibitor of DNA polymerases-alpha, -delta, and -epsilon and by butylphenyl dGTP, which blocks DNA polymerase-alpha strongly and polymerases-delta and -epsilon less effectively. However, dideoxythymidine triphosphate, a specific inhibitor of DNA polymerase-beta, did not abrogate the KGF effect. Thus KGF increases DNA repair capacity in irradiated pulmonary epithelial cells, an effect mediated at least in part by DNA polymerases-alpha, -delta, and -epsilon. Enhancement of DNA repair capability after cell damage may be one mechanism by which KGF is able to ameliorate oxidant-mediated alveolar epithelial injury.

scholarly journals Fully integrated Monte Carlo simulation for evaluating radiation induced DNA damage and subsequent repair using Geant4-DNA

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Dousatsu Sakata ◽  
Oleg Belov ◽  
Marie-Claude Bordage ◽  
Dimitris Emfietzoglou ◽  
Susanna Guatelli ◽  
...  
Keyword(s):  
Experimental Data ◽  
Dna Damage ◽  
Monte Carlo ◽  
Biological Response ◽  
Strand Break ◽  
Track Structure ◽  
Single Strand Break ◽  
Fully Integrated ◽  
Biological Responses ◽  
Radiation Induced

AbstractIonising radiation induced DNA damage and subsequent biological responses to it depend on the radiation’s track-structure and its energy loss distribution pattern. To investigate the underlying biological mechanisms involved in such complex system, there is need of predicting biological response by integrated Monte Carlo (MC) simulations across physics, chemistry and biology. Hence, in this work, we have developed an application using the open source Geant4-DNA toolkit to propose a realistic “fully integrated” MC simulation to calculate both early DNA damage and subsequent biological responses with time. We had previously developed an application allowing simulations of radiation induced early DNA damage on a naked cell nucleus model. In the new version presented in this work, we have developed three additional important features: (1) modeling of a realistic cell geometry, (2) inclusion of a biological repair model, (3) refinement of DNA damage parameters for direct damage and indirect damage scoring. The simulation results are validated with experimental data in terms of Single Strand Break (SSB) yields for plasmid and Double Strand Break (DSB) yields for plasmid/human cell. In addition, the yields of indirect DSBs are compatible with the experimental scavengeable damage fraction. The simulation application also demonstrates agreement with experimental data of $$\gamma$$ γ -H2AX yields for gamma ray irradiation. Using this application, it is now possible to predict biological response along time through track-structure MC simulations.

X-Ray Microanalysis Combined with Monte Carlo Simulation for the Analysis of Layered Thin Films: The Case of Carbon Contamination

2009 ◽  
Vol 15 (2) ◽  
pp. 99-105 ◽  
Author(s):  
Aldo Armigliato ◽  
Rodolfo Rosa
Keyword(s):  
Monte Carlo ◽  
Carbon Film ◽  
Sample Surface ◽  
Scanning Transmission Electron Microscope ◽  
Carbon Layer ◽  
Monte Carlo Code ◽  
X Ray ◽  
Transmission Electron ◽  
The Monte Carlo Method ◽  
Scanning Transmission

AbstractA previously developed Monte Carlo code has been extended to the X-ray microanalysis in a (scanning) transmission electron microscope of plan sections, consisting of bilayers and triple layers. To test the validity of this method for quantification purposes, a commercially available NiOx (x ∼ 1) thin film, deposited on a carbon layer, has been chosen. The composition and thickness of the NiO film and the thickness of the C support layer are obtained by fitting to the three X-ray intensity ratios I(NiK)/I(OK), I(NiK)/I(CK), and I(OK)/I(CK). Moreover, it has been investigated to what extent the resulting film composition is affected by the presence of a contaminating carbon film at the sample surface. To this end, the sample has been analyzed both in the (recommended) “grid downward” geometry and in the upside/down (“grid upward”) situation. It is found that a carbon contaminating film of few tens of nanometers must be assumed in both cases, in addition to the C support film. Consequently, assuming the proper C/NiOx/C stack in the simulations, the Monte Carlo method yields the correct oxygen concentration and thickness of the NiOx film.

Hydrogen peroxide-induced DNA damage in bovine lens epithelial cells

1990 ◽  
Vol 240 (1) ◽  
pp. 35-45 ◽  
Author(s):  
Norman J. Kleiman ◽  
Ren-Rong Wang ◽  
Abraham Spector
Keyword(s):  
Hydrogen Peroxide ◽  
Dna Damage ◽  
Epithelial Cells ◽  
Lens Epithelial Cells ◽  
Bovine Lens

scholarly journals Characterization of laser-driven electron and photon beams using the Monte Carlo code FLUKA

2014 ◽  
Vol 32 (2) ◽  
pp. 233-241 ◽  
Author(s):  
F. Fiorini ◽  
D. Neely ◽  
R.J. Clarke ◽  
S. Green
Keyword(s):  
Monte Carlo ◽  
Electron Temperature ◽  
Spectral Characteristics ◽  
Simulation Method ◽  
Target Thickness ◽  
Monte Carlo Code ◽  
X Rays ◽  
Photon Beams ◽  
X Ray ◽  
Plasma Effects

AbstractWe present a new simulation method to predict the maximum possible yield of X-rays produced by electron beams accelerated by petawatt lasers irradiating thick solid targets. The novelty of the method lies in the simulation of the electron refiluxing inside the target implemented with the Monte Carlo code Fluka. The mechanism uses initial theoretical electron spectra, cold targets and refiluxing electrons forced to re-enter the target iteratively. Collective beam plasma effects are not implemented in the simulation. Considering the maximum X-ray yield obtained for a given target thickness and material, the relationship between the irradiated target mass thickness and the initial electron temperature is determined, as well as the effect of the refiluxing on X-ray yield. The presented study helps to understand which electron temperature should be produced in order to generate a particular X-ray beam. Several applications, including medical and security imaging, could benefit from laser generated X-ray beams, so an understanding of the material and the thickness maximizing the yields or producing particular spectral characteristics is necessary. On the other more immediate hand, if this study is experimentally reproduced at the beginning of an experiment in which there is an interest in laser-driven electron and/or photon beams, it can be used to check that the electron temperature is as expected according to the laser parameters.

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