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Radiation-Induced DNA Damage, Repair and Responses
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Radiation-Induced DNA Damage, Repair and Responses

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biophysics".

Deadline for manuscript submissions: closed (10 August 2024) | Viewed by 7354

Special Issue Editor

Prof. Dr. Anders Brahme

E-Mail Website
Guest Editor
Department of Oncology-Pathology, Karolinska Institutet, 10074 Stockholm, Sweden
Interests: simple and complex DSB´s; role of TP53; HR and NHEJ Repair; NHEJ and HR Interactions; histone modifications; low dose apoptosis; repair fidelity; misrepair

Special Issue Information

Dear Colleagues,

The field of radiation damage and repair is rapidly advancing, with many novel molecular tools enabling the detailed investigation of both molecular processes and the advanced radiation interaction codes that determine the type of molecular damage caused to DNA. The main structure of nuclear DNA has largely been clarified in recent decades, revealing that the tetra-nucleosomes are the key component of heterochromatic DNA; however, unfortunately, research has not yet reached the calculational stage in sufficient detail. The role of Histone modifications has also opened up new dimensions regarding the epigenetic machinery involved in the DNA repair processes, in combination with the classical DNA repair players. The scope of this Special Issue includes the interesting and essential express start of DSB repair according to the initial fast Ku-DNApkcs hetero dimer, and its possible switch to the slower and more flexible MRN dimer complex for HR repair when there is high flexibility in its homology.

This Special Issue focuses on advances in the study of radiation-induced damage and the repair of cells and biomolecules. The submission of both original research articles and comprehensive reviews is welcome.

Prof. Dr. Anders Brahme
Guest Editor

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Keywords

  • MR, EM, and fish molecular imaging
  • influence of EU hetero-chromatin
  • radiation type influence
  • mutation and cancer incidence
  • therapeutic possibilities

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Published Papers (5 papers)

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Research

18 pages, 5185 KiB  
Article
TOPAS-Tissue: A Framework for the Simulation of the Biological Response to Ionizing Radiation at the Multi-Cellular Level
by Omar Rodrigo García García, Ramon Ortiz, Eduardo Moreno-Barbosa, Naoki D-Kondo, Bruce Faddegon and Jose Ramos-Méndez
Int. J. Mol. Sci. 2024, 25(18), 10061; https://doi.org/10.3390/ijms251810061 - 19 Sep 2024
Cited by 1 | Viewed by 1274
Abstract
This work aims to develop and validate a framework for the multiscale simulation of the biological response to ionizing radiation in a population of cells forming a tissue. We present TOPAS-Tissue, a framework to allow coupling two Monte Carlo (MC) codes: TOPAS with [...] Read more.
This work aims to develop and validate a framework for the multiscale simulation of the biological response to ionizing radiation in a population of cells forming a tissue. We present TOPAS-Tissue, a framework to allow coupling two Monte Carlo (MC) codes: TOPAS with the TOPAS-nBio extension, capable of handling the track-structure simulation and subsequent chemistry, and CompuCell3D, an agent-based model simulator for biological and environmental behavior of a population of cells. We verified the implementation by simulating the experimental conditions for a clonogenic survival assay of a 2-D PC-3 cell culture model (10 cells in 10,000 µm2) irradiated by MV X-rays at several absorbed dose values from 0–8 Gy. The simulation considered cell growth and division, irradiation, DSB induction, DNA repair, and cellular response. The survival was obtained by counting the number of colonies, defined as a surviving primary (or seeded) cell with progeny, at 2.7 simulated days after irradiation. DNA repair was simulated with an MC implementation of the two-lesion kinetic model and the cell response with a p53 protein-pulse model. The simulated survival curve followed the theoretical linear–quadratic response with dose. The fitted coefficients α = 0.280 ± 0.025/Gy and β = 0.042 ± 0.006/Gy2 agreed with published experimental data within two standard deviations. TOPAS-Tissue extends previous works by simulating in an end-to-end way the effects of radiation in a cell population, from irradiation and DNA damage leading to the cell fate. In conclusion, TOPAS-Tissue offers an extensible all-in-one simulation framework that successfully couples Compucell3D and TOPAS for multiscale simulation of the biological response to radiation. Full article
(This article belongs to the Special Issue Radiation-Induced DNA Damage, Repair and Responses)
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15 pages, 3781 KiB  
Article
DNA Damage and Repair in PBMCs after Internal Ex Vivo Irradiation with [223Ra]RaCl2 and [177Lu]LuCl3 Mixtures
by Isabella Strobel, Sarah Schumann, Jessica Müller, Andreas K. Buck, Matthias Port, Michael Lassmann, Uta Eberlein and Harry Scherthan
Int. J. Mol. Sci. 2024, 25(16), 8629; https://doi.org/10.3390/ijms25168629 - 7 Aug 2024
Viewed by 820
Abstract
The combination of high and low LET radionuclides has been tested in several patient studies to improve treatment response. Radionuclide mixtures can also be released in nuclear power plant accidents or nuclear bomb deployment. This study investigated the DNA damage response and DNA [...] Read more.
The combination of high and low LET radionuclides has been tested in several patient studies to improve treatment response. Radionuclide mixtures can also be released in nuclear power plant accidents or nuclear bomb deployment. This study investigated the DNA damage response and DNA double-strand break (DSB) repair in peripheral blood mononuclear cells (PBMCs) after internal exposure of blood samples of 10 healthy volunteers to either no radiation (baseline) or different radionuclide mixtures of the α- and β-emitters [223Ra]RaCl2 and [177Lu]LuCl3, i.e., 25 mGy/75 mGy, 50 mGy/50 mGy and 75 mGy/25 mGy, respectively. DSB foci and γ-H2AX α-track enumeration directly after 1 h of exposure or after 4 h or 24 h of repair revealed that radiation-induced foci (RIF) and α-track induction in 100 cells was similar for mixed α/β and pure internal α- or β-irradiation, as were the repair rates for all radiation qualities. In contrast, the fraction of unrepaired RIF (Qβ) in PBMCs after mixed α/β-irradiation (50% 223Ra & 50% 177Lu: Qβ = 0.23 ± 0.10) was significantly elevated relative to pure β-irradiation (50 mGy: Qβ, pure = 0.06 ± 0.02), with a similar trend being noted for all mixtures. This α-dose-dependent increase in persistent foci likely relates to the formation of complex DNA damage that remains difficult to repair. Full article
(This article belongs to the Special Issue Radiation-Induced DNA Damage, Repair and Responses)
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13 pages, 2301 KiB  
Article
Cumulative Dose from Recurrent CT Scans: Exploring the DNA Damage Response in Human Non-Transformed Cells
by Davide Valente, Maria Pia Gentileschi, Alessandro Valenti, Massimo Burgio, Silvia Soddu, Vicente Bruzzaniti, Antonino Guerrisi and Alessandra Verdina
Int. J. Mol. Sci. 2024, 25(13), 7064; https://doi.org/10.3390/ijms25137064 - 27 Jun 2024
Viewed by 1359
Abstract
Recurrent computed tomography (CT) examination has become a common diagnostic procedure for several diseases and injuries. Though each singular CT scan exposes individuals at low doses of low linear energy transfer (LET) radiation, the cumulative dose received from recurrent CT scans poses an [...] Read more.
Recurrent computed tomography (CT) examination has become a common diagnostic procedure for several diseases and injuries. Though each singular CT scan exposes individuals at low doses of low linear energy transfer (LET) radiation, the cumulative dose received from recurrent CT scans poses an increasing concern for potential health risks. Here, we evaluated the biological effects of recurrent CT scans on the DNA damage response (DDR) in human fibroblasts and retinal pigment epithelial cells maintained in culture for five months and subjected to four CT scans, one every four weeks. DDR kinetics and eventual accumulation of persistent-radiation-induced foci (P-RIF) were assessed by combined immunofluorescence for γH2AX and 53BP1, i.e., γH2AX/53BP1 foci. We found that CT scan repetitions significantly increased both the number and size of γH2AX/53BP1 foci. In particular, after the third CT scan, we observed the appearance of giant foci that might result from the overlapping of individual small foci and that do not associate with irreversible growth arrest, as shown by DNA replication in the foci-carrying cells. Whether these giant foci represent coalescence of unrepaired DNA damage as reported following single exposition to high doses of high LET radiation is still unclear. However, morphologically, these giant foci resemble the recently described compartmentalization of damaged DNA that should facilitate the repair of DNA double-strand breaks but also increase the risk of chromosomal translocations. Overall, these results indicate that for a correct evaluation of the damage following recurrent CT examinations, it is necessary to consider the size and composition of the foci in addition to their number. Full article
(This article belongs to the Special Issue Radiation-Induced DNA Damage, Repair and Responses)
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14 pages, 4761 KiB  
Article
Genome-Wide Profile of Mutations Induced by Carbon Ion Beam Irradiation of Dehulled Rice Seeds
by Ying Ling, Yuming Zhang, Ming Huang, Tao Guo and Guili Yang
Int. J. Mol. Sci. 2024, 25(10), 5195; https://doi.org/10.3390/ijms25105195 - 10 May 2024
Viewed by 807
Abstract
As a physical mutagen, carbon ion beam (CIB) irradiation can induce high-frequency mutation, which is user-friendly and environment-friendly in plant breeding. In this study, we resequenced eight mutant lines which were screened out from the progeny of the CIB-irradiated dehulled rice seeds. Among [...] Read more.
As a physical mutagen, carbon ion beam (CIB) irradiation can induce high-frequency mutation, which is user-friendly and environment-friendly in plant breeding. In this study, we resequenced eight mutant lines which were screened out from the progeny of the CIB-irradiated dehulled rice seeds. Among these mutants, CIB induced 135,535 variations, which include single base substitutions (SBSs), and small insertion and deletion (InDels). SBSs are the most abundant mutation, and account for 88% of all variations. Single base conversion is the main type of SBS, and the average ratio of transition and transversion is 1.29, and more than half of the InDels are short-segmented mutation (1–2 bp). A total of 69.2% of the SBSs and InDels induced by CIBs occurred in intergenic regions on the genome. Surprisingly, the average mutation frequency in our study is 9.8 × 10−5/bp and much higher than that of the previous studies, which may result from the relatively high irradiation dosage and the dehulling of seeds for irradiation. By analyzing the mutation of every 1 Mb in the genome of each mutant strain, we found some unusual high-frequency (HF) mutation regions, where SBSs and InDels colocalized. This study revealed the mutation mechanism of dehulled rice seeds by CIB irradiation on the genome level, which will enrich our understanding of the mutation mechanism of CIB radiation and improve mutagenesis efficiency. Full article
(This article belongs to the Special Issue Radiation-Induced DNA Damage, Repair and Responses)
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13 pages, 3214 KiB  
Article
Foci-Xpress: Automated and Fast Nuclear Foci Counting Tool
by Jae-I Moon, Woo-Jin Kim, Ki-Tae Kim, Hyun-Jung Kim, Hye-Rim Shin, Heein Yoon, Seung Gwa Park, Min-Sang Park, Young-Dan Cho, Pil-Jong Kim and Hyun-Mo Ryoo
Int. J. Mol. Sci. 2023, 24(19), 14465; https://doi.org/10.3390/ijms241914465 - 23 Sep 2023
Cited by 1 | Viewed by 2356
Abstract
In the nucleus, distinct, discrete spots or regions called “foci” have been identified, each harboring a specific molecular function. Accurate and efficient quantification of these foci is essential for understanding cellular dynamics and signaling pathways. In this study, we present an innovative automated [...] Read more.
In the nucleus, distinct, discrete spots or regions called “foci” have been identified, each harboring a specific molecular function. Accurate and efficient quantification of these foci is essential for understanding cellular dynamics and signaling pathways. In this study, we present an innovative automated image analysis method designed to precisely quantify subcellular foci within the cell nucleus. Manual foci counting methods can be tedious and time-consuming. To address these challenges, we developed an open-source software that automatically counts the number of foci from the indicated image files. We compared the foci counting efficiency, velocity, accuracy, and convenience of Foci-Xpress with those of other conventional methods in foci-induced models. We can adjust the brightness of foci to establish a threshold. The Foci-Xpress method was significantly faster than other conventional methods. Its accuracy was similar to that of conventional methods. The most significant strength of Foci-Xpress is automation, which eliminates the need for analyzing equipment while counting. This enhanced throughput facilitates comprehensive statistical analyses and supports robust conclusions from experiments. Furthermore, automation completely rules out biases caused by researchers, such as manual errors or daily variations. Thus, Foci-Xpress is a convincing, convenient, and easily accessible focus-counting tool for cell biologists. Full article
(This article belongs to the Special Issue Radiation-Induced DNA Damage, Repair and Responses)
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