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Special Issue "Radiation Damage in Biomolecules and Cells"

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: 31 January 2020.

Special Issue Editors

Dr. Francesca Ballarini
E-Mail Website
Guest Editor
1. Physics Department, University of Pavia, Pavia, Italy
2. Istituto Nazionale di Fisica Nucleare – Sezione di Pavia, Pavia, Italy
Interests: (modelling) the action of ionizing radiation in biological targets, with focus on DNA/chromosome damage and cell death,
Dr. Mario Pietro Carante
E-Mail Website
Guest Editor
1. Physics Department, University of Pavia, Pavia, Italy
2. Istituto Nazionale di Fisica Nucleare – Sezione di Pavia, Pavia, Italy
Interests: ionizing radiation, radiobiology, hadron therapy, nuclear physics

Special Issue Information

Dear Colleagues,

Ionizing radiation is widely used in medicine, both as a diagnostic tool and as a therapeutic agent. Furthermore, several exposure scenarios (e.g., occupational exposure, radon, space radiation) raise radiation protection issues. It is therefore mandatory for the scientific community to continuously update and improve the knowledge of the mechanisms governing the induction of radiation effects in biological targets and to apply the acquired information to optimize the medical use of radiation as well as the protecting strategies.

For instance, although the DNA is widely recognized as the main target of radiation, the features of the critical DNA damage type(s) leading to cell death or cell conversion to malignancy are still unclear; in addition, the role played by other targets (which may be involved in bystander effects and other low-dose phenomena) deserves further investigation. Among the many possible medical applications, different aspects of hadron therapy should be further addressed, including a more and more accurate RBE evaluation and the use of alternative sources like He and O ions. Such investigations can be carried out both experimentally, by means of in vitro and in vivo studies, and theoretically, by biophysical models and simulation codes.

This Special Issue on “Radiation damage in biomolecules and cells” is open to researchers working (both experimentally and theoretically) on the effects of ionizing radiation at the molecular and cellular levels. We welcome papers on the different types of DNA/chromosome/cell damage, addressing the underlying mechanisms and/or the dependence on dose, dose–rate, radiation quality, cell type, etc., as well as the possible implications for radiotherapy and radiation protection.

Dr. Francesca Ballarini
Dr. Mario Pietro Carante
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Ionizing radiation
  • DNA damage
  • Chromosome aberrations
  • Cell death
  • Hadron therapy
  • Radiation protection
  • Biophysical models
  • Computational radiobiology

Published Papers (5 papers)

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Research

Open AccessArticle
Impact of Target Oxygenation on the Chemical Track Evolution of Ion and Electron Radiation
Int. J. Mol. Sci. 2020, 21(2), 424; https://doi.org/10.3390/ijms21020424 - 09 Jan 2020
Abstract
The radiosensitivity of biological systems is strongly affected by the system oxygenation. On the nanoscopic scale and molecular level, this effect is considered to be strongly related to the indirect damage of radiation. Even though particle track radiolysis has been the object of [...] Read more.
The radiosensitivity of biological systems is strongly affected by the system oxygenation. On the nanoscopic scale and molecular level, this effect is considered to be strongly related to the indirect damage of radiation. Even though particle track radiolysis has been the object of several studies, still little is known about the nanoscopic impact of target oxygenation on the radical yields. Here we present an extension of the chemical module of the Monte Carlo particle track structure code TRAX, taking into account the presence of dissolved molecular oxygen in the target material. The impact of the target oxygenation level on the chemical track evolution and the yields of all the relevant chemical species are studied in water under different irradiation conditions: different linear energy transfer (LET) values, different oxygenation levels, and different particle types. Especially for low LET radiation, a large production of two highly toxic species ( HO 2 and O 2 ), which is not produced in anoxic conditions, is predicted and quantified in oxygenated solutions. The remarkable correlation between the HO 2 and O 2 production yield and the oxygen enhancement ratio observed in biological systems suggests a direct or indirect involvement of HO 2 and O 2 in the oxygen sensitization effect. The results are in agreement with available experimental data and previous computational approaches. An analysis of the oxygen depletion rate in different radiation conditions is also reported. The radiosensitivity of biological systems is strongly affected by the system oxygenation. On the nanoscopic scale and molecular level, this effect is considered to be strongly related to the indirect damage of radiation. Even though particle track radiolysis has been the object of several studies, still little is known about the nanoscopic impact of target oxygenation on the radical yields. Here we present an extension of the chemical module of the Monte Carlo particle track structure code TRAX, taking into account the presence of dissolved molecular oxygen in the target material. The impact of the target oxygenation level on the chemical track evolution and the yields of all the relevant chemical species are studied in water under different irradiation conditions: different linear energy transfer (LET) values, different oxygenation levels, and different particle types. Especially for low LET radiation, a large production of two highly toxic species ( HO 2 and O 2 ), which is not produced in anoxic conditions, is predicted and quantified in oxygenated solutions. The remarkable correlation between the HO 2 and O 2 production yield and the oxygen enhancement ratio observed in biological systems suggests a direct or indirect involvement of HO 2 and O 2 in the oxygen sensitization effect. The results are in agreement with available experimental data and previous computational approaches. An analysis of the oxygen depletion rate in different radiation conditions is also reported. Full article
(This article belongs to the Special Issue Radiation Damage in Biomolecules and Cells)
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Open AccessArticle
Assessment of Radio-Induced Damage in Endothelial Cells Irradiated with 40 kVp, 220 kVp, and 4 MV X-rays by Means of Micro and Nanodosimetric Calculations
Int. J. Mol. Sci. 2019, 20(24), 6204; https://doi.org/10.3390/ijms20246204 - 09 Dec 2019
Abstract
The objective of this work was to study the differences in terms of early biological effects that might exist between different X-rays energies by using a mechanistic approach. To this end, radiobiological experiments exposing cell monolayers to three X-ray energies were performed in [...] Read more.
The objective of this work was to study the differences in terms of early biological effects that might exist between different X-rays energies by using a mechanistic approach. To this end, radiobiological experiments exposing cell monolayers to three X-ray energies were performed in order to assess the yields of early DNA damage, in particular of double-strand breaks (DSBs). The simulation of these irradiations was set in order to understand the differences in the obtained experimental results. Hence, simulated results in terms of microdosimetric spectra and early DSB induction were analyzed and compared to the experimental data. Human umbilical vein endothelial cells (HUVECs) were irradiated with 40, 220 kVp, and 4 MV X-rays. The Geant4 Monte Carlo simulation toolkit and its extension Geant4-DNA were used for the simulations. Microdosimetric calculations aiming to determine possible differences in the variability of the energy absorbed by the irradiated cell population for those photon spectra were performed on 10,000 endothelial cell nuclei representing a cell monolayer. Nanodosimetric simulations were also carried out using a computation chain that allowed the simulation of physical, physico-chemical, and chemical stages on a single realistic endothelial cell nucleus model including both heterochromatin and euchromatin. DNA damage was scored in terms of yields of prompt DSBs per Gray (Gy) and per giga (109) base pair (Gbp) and DSB complexity was derived in order to be compared to experimental data expressed as numbers of histone variant H2AX (γ-H2AX) foci per cell. The calculated microdosimetric spread in the irradiated cell population was similar when comparing between 40 and 220 kVp X-rays and higher when comparing with 4 MV X-rays. Simulated yields of induced DSB/Gy/Gbp were found to be equivalent to those for 40 and 220 kVp but larger than those for 4 MV, resulting in a relative biological effectiveness (RBE) of 1.3. Additionally, DSB complexity was similar between the considered photon spectra. Simulated results were in good agreement with experimental data obtained by IRSN (Institut de radioprotection et de sûreté nucléaire) radiobiologists. Despite differences in photon energy, few differences were observed when comparing between 40 and 220 kVp X-rays in microdosimetric and nanodosimetric calculations. Nevertheless, variations were observed when comparing between 40/220 kVp and 4 MV X-rays. Thanks to the simulation results, these variations were able to be explained by the differences in the production of secondary electrons with energies below 10 keV. Full article
(This article belongs to the Special Issue Radiation Damage in Biomolecules and Cells)
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Open AccessArticle
Modeling the Effect of Hypoxia and DNA Repair Inhibition on Cell Survival after Photon Irradiation
Int. J. Mol. Sci. 2019, 20(23), 6054; https://doi.org/10.3390/ijms20236054 - 30 Nov 2019
Abstract
Mechanistic approaches to modeling the effects of ionizing radiation on cells are on the rise, promising a better understanding of predictions and higher flexibility concerning conditions to be accounted for. In this work we modified and extended a previously published mechanistic model of [...] Read more.
Mechanistic approaches to modeling the effects of ionizing radiation on cells are on the rise, promising a better understanding of predictions and higher flexibility concerning conditions to be accounted for. In this work we modified and extended a previously published mechanistic model of cell survival after photon irradiation under hypoxia to account for radiosensitization caused by deficiency or inhibition of DNA damage repair enzymes. The model is shown to be capable of describing the survival data of cells with DNA damage repair deficiency, both under norm- and hypoxia. We find that our parameterization of radiosensitization is invariant under change of oxygen status, indicating that the relevant parameters for both mechanisms can be obtained independently and introduced freely to the model to predict their combined effect. Full article
(This article belongs to the Special Issue Radiation Damage in Biomolecules and Cells)
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Open AccessArticle
Radiation-Stimulated Translocation of CD166 and CRYAB to the Endothelial Surface Provides Potential Vascular Targets on Irradiated Brain Arteriovenous Malformations
Int. J. Mol. Sci. 2019, 20(23), 5830; https://doi.org/10.3390/ijms20235830 - 20 Nov 2019
Abstract
Vascular targeting with pro-thrombotic antibody-conjugates is a promising biological treatment for brain arteriovenous malformations (bAVMs). However, targeted drug delivery relies on the identification of unique or overexpressed markers on the surface of a target cell. In the absence of inherent biological markers, stereotactic [...] Read more.
Vascular targeting with pro-thrombotic antibody-conjugates is a promising biological treatment for brain arteriovenous malformations (bAVMs). However, targeted drug delivery relies on the identification of unique or overexpressed markers on the surface of a target cell. In the absence of inherent biological markers, stereotactic radiosurgery may be used to prime induction of site-specific and targetable molecular changes on the endothelial surface. To investigate lumen-accessible, endothelial targets induced by radiation, we combined Gamma knife surgery in an AVM animal model with in vivo biotin-labeling and comparative proteomics. Two proteins, αB-crystallin (CRYAB)—a small heat shock protein that normally acts as an intracellular chaperone to misfolded proteins—and activated leukocyte cell adhesion molecule CD166, were further validated for endothelial surface expression after irradiation. Immunostaining of endothelial cells in vitro and rat AVM tissue ex vivo confirmed de novo induction of CRYAB following irradiation (20 Gy). Western analysis demonstrated that CRYAB accumulated intracellularly as a 20 kDa monomer, but, at the cell surface, a novel 65 kDa protein was observed, suggesting radiation stimulates translocation of an atypical CRYAB isoform. In contrast, CD166 had relatively high expression in non-irradiated cells, localized predominantly to the lateral surfaces. Radiation increased CD166 surface exposure by inducing translocation from intercellular junctions to the apical surface without significantly altering total protein levels. These findings reinforce the dynamic molecular changes induced by radiation exposure, particularly at the cell surface, and support further investigation of radiation as a priming mechanism and these molecules as putative targets for focused drug delivery in irradiated tissue. Full article
(This article belongs to the Special Issue Radiation Damage in Biomolecules and Cells)
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Open AccessArticle
Proton Therapy and Src Family Kinase Inhibitor Combined Treatments on U87 Human Glioblastoma Multiforme Cell Line
Int. J. Mol. Sci. 2019, 20(19), 4745; https://doi.org/10.3390/ijms20194745 - 24 Sep 2019
Abstract
Glioblastoma Multiforme (GBM) is the most common of malignant gliomas in adults with an exiguous life expectancy. Standard treatments are not curative and the resistance to both chemotherapy and conventional radiotherapy (RT) plans is the main cause of GBM care failures. Proton therapy [...] Read more.
Glioblastoma Multiforme (GBM) is the most common of malignant gliomas in adults with an exiguous life expectancy. Standard treatments are not curative and the resistance to both chemotherapy and conventional radiotherapy (RT) plans is the main cause of GBM care failures. Proton therapy (PT) shows a ballistic precision and a higher dose conformity than conventional RT. In this study we investigated the radiosensitive effects of a new targeted compound, SRC inhibitor, named Si306, in combination with PT on the U87 glioblastoma cell line. Clonogenic survival assay, dose modifying factor calculation and linear-quadratic model were performed to evaluate radiosensitizing effects mediated by combination of the Si306 with PT. Gene expression profiling by microarray was also conducted after PT treatments alone or combined, to identify gene signatures as biomarkers of response to treatments. Our results indicate that the Si306 compound exhibits a radiosensitizing action on the U87 cells causing a synergic cytotoxic effect with PT. In addition, microarray data confirm the SRC role as the main Si306 target and highlights new genes modulated by the combined action of Si306 and PT. We suggest, the Si306 as a new candidate to treat GBM in combination with PT, overcoming resistance to conventional treatments. Full article
(This article belongs to the Special Issue Radiation Damage in Biomolecules and Cells)
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