scholarly journals The Effects of Dimethylsulfoxide and Oxygen on DNA Damage Induction and Repair Outcomes for Cells Irradiated by 62 MeV Proton and 3.31 MeV Helium Ions

2021 ◽  
Vol 11 (4) ◽  
pp. 286
Author(s):  
Chun-Chieh Chan ◽  
Ya-Yun Hsiao
Keyword(s):  
Dna Damage ◽  
Monte Carlo ◽  
Mutation Frequency ◽  
Excision Repair ◽  
Biological Effects ◽  
Helium Ions ◽  
Proton Beams ◽  
Normal Tissues ◽  
Radiation Induced ◽  
Damage Simulation

Reactive oxygen species (ROS) play an essential role in radiation-induced indirect actions. In terms of DNA damage, double strand breaks (DSBs) have the greatest effects on the repair of DNA damage, cell survival and transformation. This study evaluated the biological effects of the presence of ROS and oxygen on DSB induction and mutation frequency. The relative biological effectiveness (RBE) and oxygen enhancement ratio (OER) of 62 MeV therapeutic proton beams and 3.31 MeV helium ions were calculated using Monte Carlo damage simulation (MCDS) software. Monte Carlo excision repair (MCER) simulations were used to calculate the repair outcomes (mutation frequency). The RBE values of proton beams decreased to 0.75 in the presence of 0.4 M dimethylsulfoxide (DMSO) and then increases to 0.9 in the presence of 2 M DMSO while the RBE values of 3.31 MeV helium ions increased from 2.9 to 5.7 (0‒2 M). The mutation frequency of proton beams also decreased from 0.008‒0.065 to 0.004‒0.034 per cell per Gy by the addition of 2 M DMSO, indicating that ROS affects both DSB induction and repair outcomes. These results show that the combined use of DMSO in normal tissues and an increased dose in tumor regions increases treatment efficiency.

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.

scholarly journals Thepol3-tHyperrecombination Phenotype and DNA Damage-Induced Recombination inSaccharomyces cerevisiaeIsRAD50Dependent

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Alvaro Galli ◽  
Kurt Hafer ◽  
Tiziana Cervelli ◽  
Robert H. Schiestl
Keyword(s):  
Dna Damage ◽  
Base Excision Repair ◽  
Excision Repair ◽  
Restrictive Temperature ◽  
Repair Gene ◽  
Intrachromosomal Recombination ◽  
Radiation Induced ◽  
Base Excision ◽  
Spontaneous Frequency ◽  
Elevated Frequency

The DNA polymeraseδ(POL3/CDC2) allelepol3-tofSaccharomyces cerevisiaehas previously been shown to be sensitive to methylmethanesulfonate (MMS) and has been proposed to be involved in base excision repair. Our results, however, show that thepol3-tmutation is synergistic for MMS sensitivity withMAG1, a known base excision repair gene, but it is epistatic withrad50Δ, suggesting thatPOL3may be involved not only in base excision repair but also in a RAD50 dependent function. We further studied the interaction ofpol3-twithrad50Δby examining their effect on spontaneous, MMS-, UV-, and ionizing radiation-induced intrachromosomal recombination. We found thatrad50Δcompletely abolishes the elevated spontaneous frequency of intrachromosomal recombination in thepol3-tmutant and significantly decreases UV- and MMS-induced recombination in bothPOL3andpol3-tstrains. Interestingly,rad50Δhad no effect onγ-ray-induced recombination in both backgrounds between 0 and 50 Gy. Finally, the deletion ofRAD50had no effect on the elevated frequency of homologous integration conferred by thepol3-tmutation.RAD50is possibly involved in resolution of replication forks that are stalled by mutagen-induced external DNA damage, or internal DNA damage produced by growing thepol3-tmutant at the restrictive temperature.

The role of nucleotide excision repair of Escherichia coli in repair of spontaneous and gamma-radiation-induced DNA damage in the lacZα gene

2000 ◽  
Vol 460 (2) ◽  
pp. 117-125 ◽  
Author(s):  
Gitta K Kuipers ◽  
Ben J Slotman ◽  
Hester A Poldervaart ◽  
Ingrid M.J van Vilsteren ◽  
Carola A Reitsma-Wijker ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Damage ◽  
Gamma Radiation ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Nucleotide Excision ◽  
Radiation Induced

scholarly journals MicroRNA-222 alleviates radiation-induced apoptosis by targeting BCL2L11 in cochlea hair cells

2021 ◽  
Author(s):  
Yan-yan Zhang ◽  
Gao-yun Xiong ◽  
Xiao-xing Xie
Keyword(s):  
Dna Damage ◽  
Hair Cell ◽  
Cell Injury ◽  
Biological Effects ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Protective Effects ◽  
Radiation Induced ◽  
Induced Apoptosis

Radiation-induced hair cell injury is detrimental for human health but the underlying mechanism is not clear. MicroRNAs (miRNAs) have critical roles in various types of cellular biological processes. The present study investigated the role of miR-222 in the regulation of ionizing radiation (IR)-induced cell injury in auditory cells and its underlying mechanism. Real time PCR was performed to identify the expression profile of miR-222 in the cochlea hair cell line HEI-OC1 after IR exposure. miRNA mimics or inhibitor-mediated upregulation or downregulation of indicated miRNA was applied to characterize the biological effects of miR-222 using MTT, apoptosis and DNA damage assay. Bioinformatic analyses and luciferase reporter assays were applied to identify a miRNA target gene. Our study confirmed that IR treatment significantly suppressed miR-222 levels in a dose-dependent manner. Upregulation of miR-222 enhances cell viability and alleviated IR-induced apoptosis and DNA damage in HEI-OC1 cells. In addition, BCL-2-like protein 11 (BCL2L11) was validated as a direct target of miR-222. Overexpression of BCL2L11 abolished the protective effects of miR-222 in IR-treated HEI-OC1 cells. Moreover, miR-222 alleviated IR-induced apoptosis and DNA damage by directly targeting BCL2L11.The present study demonstrates that miR-222 exhibits protective effects against irradiation‑induced cell injury by directly targeting BCL2L11 in cochlear cells.

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