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Epigenetic Effects and Non-DNA Targets of Ionizing Radiation
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Epigenetic Effects and Non-DNA Targets of Ionizing Radiation

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 (29 October 2021) | Viewed by 22611

Special Issue Editors

Dr. Mauro Belli

E-Mail Website
Guest Editor
Independent Researcher, 00185 Rome, Italy
Interests: radiation biology; radiation effects; DNA damage; DNA repair; charged particles; radiation protection; low doses; radiation therapy; hadrontherapy; radiation epigenetics
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Antonella Sgura

E-Mail Website
Guest Editor
Department of Sciences, Università Roma Tre, Viale G. Marconi 446, 00146 Rome, Italy
Interests: ionizing radiation; electromagnetic waves; radiation biology; chromosome aberrations; micronuclei induction; chromosome structure; cellular senescence
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Radiation science, in particular that dealing with ionizing radiation, is a relatively recent discipline, since our scientific community first became aware of it just a little over a century ago, with the discovery of X-rays and natural radioactivity. After some initial enthusiastic attempts to treat nearly every kind of illness or discomfort with this radiation, the discovery of its harmful effects brought its practical applications in health sciences to a fork, separating them into radiation therapy and radiation protection. In both cases, the underlying basic mechanisms are almost always assumed to be related to the “radiation damage” of the DNA in the irradiated cells.

However, in recent decades, evidence of the non-DNA targeted effects of ionizing radiation, such as bystander/abscopal effects and adaptive response, have raised concerns about the magnitude of low-dose radiation risk and supported the view that radiation induces cell response other than “radiation damage”. Epigenetic and other non-DNA-targeted effects appear to be related and involved in a variety of cell responses to ionizing radiation, including mitochondrial and extranuclear modifications and triggering of defense mechanisms of the cell. Therefore, even though the existence of radiation-induced DNA damage is not in doubt, it must be considered that the cellular and molecular modifications following radiation exposure are much more complex, and particularly relevant at low doses.

This Special Issue is focused on collecting significant works on this topic, including original research, reviews, and commentaries, so as to provide an open-source of information that can help to formulate a more comprehensive and broader view of cellular and molecular response to ionizing radiation, which will be useful not only for the advancement of radiation biology but also for applications in radiation protection and therapy.

Dr. Mauro Belli
Prof. Antonella Sgura
Guest Editors

Manuscript Submission Information

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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.

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Keywords

  • Adaptive response
  • Bystander effect
  • Chromatin structure
  • DNA damage
  • DNA methylation
  • DNA repair
  • Epigenetics
  • Genome instability
  • Ionizing radiation
  • Non-coding RNA
  • Non-targeted effects
  • Senescence

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Published Papers (4 papers)

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Research

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17 pages, 4247 KiB  
Article
Effects of the Combined Treatment with a G-Quadruplex-Stabilizing Ligand and Photon Beams on Glioblastoma Stem-like Cells: A Magnetic Resonance Study
by Alessandra Palma, Sveva Grande, Anna Maria Luciani, Lucia Ricci-Vitiani, Mariachiara Buccarelli, Roberto Pallini, Alice Triveri, Valentina Pirota, Filippo Doria, Quintino Giorgio D’Alessandris, Francesco Berardinelli, Antonio Antoccia and Antonella Rosi
Int. J. Mol. Sci. 2021, 22(23), 12709; https://doi.org/10.3390/ijms222312709 - 24 Nov 2021
Cited by 1 | Viewed by 2077
Abstract
Glioblastoma multiforme is a malignant primary brain tumor with a poor prognosis and high rates of chemo-radiotherapy failure, mainly due to a small cell fraction with stem-like properties (GSCs). The mechanisms underlying GSC response to radiation need to be elucidated to enhance sensitivity [...] Read more.
Glioblastoma multiforme is a malignant primary brain tumor with a poor prognosis and high rates of chemo-radiotherapy failure, mainly due to a small cell fraction with stem-like properties (GSCs). The mechanisms underlying GSC response to radiation need to be elucidated to enhance sensitivity to treatments and to develop new therapeutic strategies. In a previous study, two GSC lines, named line #1 and line #83, responded differently to carbon ions and photon beams, with the differences likely attributable to their own different metabolic fingerprint rather than to radiation type. Data from the literature showed the capability of RHPS4, a G-quadruplex stabilizing ligand, to sensitize the glioblastoma radioresistant U251MG cells to X-rays. The combined metabolic effect of ligand #190, a new RHPS4-derivative showing reduced cardiotoxicity, and a photon beam has been monitored by magnetic resonance (MR) spectroscopy for the two GSC lines, #1 and #83, to reveal whether a synergistic response occurs. MR spectra from both lines were affected by single and combined treatments, but the variations of the analysed metabolites were statistically significant mainly in line #1, without synergistic effects due to combination. The multivariate analysis of ten metabolites shows a separation between control and treated samples in line #1 regardless of treatment type, while separation was not detected in line #83. Full article
(This article belongs to the Special Issue Epigenetic Effects and Non-DNA Targets of Ionizing Radiation)
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Review

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59 pages, 2366 KiB  
Review
Role of Mitochondria in Radiation Responses: Epigenetic, Metabolic, and Signaling Impacts
by Dietrich Averbeck and Claire Rodriguez-Lafrasse
Int. J. Mol. Sci. 2021, 22(20), 11047; https://doi.org/10.3390/ijms222011047 - 13 Oct 2021
Cited by 98 | Viewed by 10590
Abstract
Until recently, radiation effects have been considered to be mainly due to nuclear DNA damage and their management by repair mechanisms. However, molecular biology studies reveal that the outcomes of exposures to ionizing radiation (IR) highly depend on activation and regulation through other [...] Read more.
Until recently, radiation effects have been considered to be mainly due to nuclear DNA damage and their management by repair mechanisms. However, molecular biology studies reveal that the outcomes of exposures to ionizing radiation (IR) highly depend on activation and regulation through other molecular components of organelles that determine cell survival and proliferation capacities. As typical epigenetic-regulated organelles and central power stations of cells, mitochondria play an important pivotal role in those responses. They direct cellular metabolism, energy supply and homeostasis as well as radiation-induced signaling, cell death, and immunological responses. This review is focused on how energy, dose and quality of IR affect mitochondria-dependent epigenetic and functional control at the cellular and tissue level. Low-dose radiation effects on mitochondria appear to be associated with epigenetic and non-targeted effects involved in genomic instability and adaptive responses, whereas high-dose radiation effects (>1 Gy) concern therapeutic effects of radiation and long-term outcomes involving mitochondria-mediated innate and adaptive immune responses. Both effects depend on radiation quality. For example, the increased efficacy of high linear energy transfer particle radiotherapy, e.g., C-ion radiotherapy, relies on the reduction of anastasis, enhanced mitochondria-mediated apoptosis and immunogenic (antitumor) responses. Full article
(This article belongs to the Special Issue Epigenetic Effects and Non-DNA Targets of Ionizing Radiation)
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15 pages, 618 KiB  
Review
Evaluation of Epigenetic and Radiomodifying Effects during Radiotherapy Treatments in Zebrafish
by Gaia Pucci, Giusi Irma Forte and Vincenzo Cavalieri
Int. J. Mol. Sci. 2021, 22(16), 9053; https://doi.org/10.3390/ijms22169053 - 22 Aug 2021
Cited by 4 | Viewed by 2679
Abstract
Radiotherapy is still a long way from personalizing cancer treatment plans, and its effectiveness depends on the radiosensitivity of tumor cells. Indeed, therapies that are efficient and successful for some patients may be relatively ineffective for others. Based on this, radiobiological research is [...] Read more.
Radiotherapy is still a long way from personalizing cancer treatment plans, and its effectiveness depends on the radiosensitivity of tumor cells. Indeed, therapies that are efficient and successful for some patients may be relatively ineffective for others. Based on this, radiobiological research is focusing on the ability of some reagents to make cancer cells more responsive to ionizing radiation, as well as to protect the surrounding healthy tissues from possible side effects. In this scenario, zebrafish emerged as an effective model system to test for radiation modifiers that can potentially be used for radiotherapeutic purposes in humans. The adoption of this experimental organism is fully justified and supported by the high similarity between fish and humans in both their genome sequences and the effects provoked in them by ionizing radiation. This review aims to provide the literature state of the art of zebrafish in vivo model for radiobiological studies, particularly focusing on the epigenetic and radiomodifying effects produced during fish embryos’ and larvae’s exposure to radiotherapy treatments. Full article
(This article belongs to the Special Issue Epigenetic Effects and Non-DNA Targets of Ionizing Radiation)
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16 pages, 1091 KiB  
Review
Molecular Hydrogen as a Potential Clinically Applicable Radioprotective Agent
by Shin-ichi Hirano, Yusuke Ichikawa, Bunpei Sato, Haru Yamamoto, Yoshiyasu Takefuji and Fumitake Satoh
Int. J. Mol. Sci. 2021, 22(9), 4566; https://doi.org/10.3390/ijms22094566 - 27 Apr 2021
Cited by 23 | Viewed by 5838
Abstract
Although ionizing radiation (radiation) is commonly used for medical diagnosis and cancer treatment, radiation-induced damages cannot be avoided. Such damages can be classified into direct and indirect damages, caused by the direct absorption of radiation energy into DNA and by free radicals, such [...] Read more.
Although ionizing radiation (radiation) is commonly used for medical diagnosis and cancer treatment, radiation-induced damages cannot be avoided. Such damages can be classified into direct and indirect damages, caused by the direct absorption of radiation energy into DNA and by free radicals, such as hydroxyl radicals (•OH), generated in the process of water radiolysis. More specifically, radiation damage concerns not only direct damages to DNA, but also secondary damages to non-DNA targets, because low-dose radiation damage is mainly caused by these indirect effects. Molecular hydrogen (H2) has the potential to be a radioprotective agent because it can selectively scavenge •OH, a reactive oxygen species with strong oxidizing power. Animal experiments and clinical trials have reported that H2 exhibits a highly safe radioprotective effect. This paper reviews previously reported radioprotective effects of H2 and discusses the mechanisms of H2, not only as an antioxidant, but also in intracellular responses including anti-inflammation, anti-apoptosis, and the regulation of gene expression. In doing so, we demonstrate the prospects of H2 as a novel and clinically applicable radioprotective agent. Full article
(This article belongs to the Special Issue Epigenetic Effects and Non-DNA Targets of Ionizing Radiation)
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