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Advances in Radiation Toxicity

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

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 23477

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Special Issue Editor

Prof. Dr. Andreyan N. Osipov

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Guest Editor

State Research Center-Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC), 123098 Moscow, Russia
Interests: DNA damage and repair; DNA double-strand breaks; cell death; cellular radiobiology; genotoxicity; carcinogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Radiation includes electromagnetic waves (from γ- and X-ray to radio wave range) and particles (from subatomic to ion). Different types of ionizing and non-ionizing radiation induce wide spectrum of biological effects from beneficial to detrimental including lethal. This Special Issue highlights latest advances in molecular mechanisms of cell toxicity, radiation effects with the focus on DNA damage and repair, cell death, signal transduction, transcription and translation regulation, epigenetic rearrangement, and how they convert to cancer and non-cancer disease. We therefore invite submissions of research articles and reviews addressing pertaining knowledge in radiation toxicity. The specific topics covered include but not limited to:

Radiation-induced DNA damage and repair;
Cell death mechanisms;
Radiation mutagenesis and carcinogenesis;
Mechanisms of non-cancer radiation diseases;
Responses to internal radionuclide irradiation;
Advances in space biomedicine;
Heavy ion radiobiology;
Electromagnetic radiation effects, including UV and cell phone radiation;
Laser radiation toxicity;
Ultrashort radiation effects

Prof. Dr. Andreyan N. Osipov
Guest Editor

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 submissions that pass pre-check are 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
electromagnetic radiation
space radiation
laser radiation
ultrashort radiation
DNA damage and repair
cellular radiation effects
mutagenesis and carcinogenesis
non-cancer radiation effects

Published Papers (10 papers)

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Research

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22 pages, 3837 KiB

Open AccessArticle

Effects of Fractionated Radiation Exposure on Vimentin Expression in Cervical Cancers: Analysis of Association with Cancer Stem Cell Response and Short-Term Prognosis

by Irina Zamulaeva, Olga Matchuk, Elena Selivanova, Liana Mkrtchian, Anna Yakimova, Victoria Gusarova, Nikita Lipunov, Liudmila Krikunova, Sergey Ivanov and Andrey Kaprin

Int. J. Mol. Sci. 2023, 24(4), 3271; https://doi.org/10.3390/ijms24043271 - 7 Feb 2023

Cited by 1 | Viewed by 1392

Abstract

Elucidation of the mechanisms for the response of cancer stem cells (CSCs) to radiation exposure is of considerable interest for further improvement of radio- and chemoradiotherapy of cervical cancer (CC). The aim of this work is to evaluate the effects of fractionated radiation exposure on the expression of vimentin, which is one of the end-stage markers of epithelial-mesenchymal transition (EMT), and analyze its association with CSC radiation response and short-term prognosis of CC patients. The level of vimentin expression was determined in HeLa, SiHa cell lines, and scrapings from the cervix of 46 CC patients before treatment and after irradiation at a total dose of 10 Gy using real-time polymerase chain reaction (PCR) assay, flow cytometry, and fluorescence microscopy. The number of CSCs was assessed using flow cytometry. Significant correlations were shown between vimentin expression and postradiation changes in CSC numbers in both cell lines (R = 0.88, p = 0.04 for HeLa and R = 0.91, p = 0.01 for SiHa) and cervical scrapings (R = 0.45, p = 0.008). Associations were found at the level of tendency between postradiation increase in vimentin expression and unfavorable clinical outcome 3–6 months after treatment. The results clarify some of the relationships between EMT, CSCs, and therapeutic resistance that are needed to develop new strategies for cancer treatment. Full article

(This article belongs to the Special Issue Advances in Radiation Toxicity)

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16 pages, 2608 KiB

Open AccessArticle

Mitogen-like Cerium-Based Nanoparticles Protect Schmidtea mediterranea against Severe Doses of X-rays

by Kristina O. Filippova, Artem M. Ermakov, Anton L. Popov, Olga N. Ermakova, Artem S. Blagodatsky, Nikita N. Chukavin, Alexander B. Shcherbakov, Alexander E. Baranchikov and Vladimir K. Ivanov

Int. J. Mol. Sci. 2023, 24(2), 1241; https://doi.org/10.3390/ijms24021241 - 8 Jan 2023

Cited by 4 | Viewed by 1895

Abstract

Novel radioprotectors are strongly demanded due to their numerous applications in radiobiology and biomedicine, e.g., for facilitating the remedy after cancer radiotherapy. Currently, cerium-containing nanomaterials are regarded as promising inorganic radioprotectors due to their unrivaled antioxidant activity based on their ability to mimic the action of natural redox enzymes like catalase and superoxide dismutase and to neutralize reactive oxygen species (ROS), which are by far the main damaging factors of ionizing radiation. The freshwater planarian flatworms are considered a promising system for testing new radioprotectors, due to the high regenerative potential of these species and an excessive amount of proliferating stem cells (neoblasts) in their bodies. Using planarian Schmidtea mediterranea, we tested CeO₂ nanoparticles, well known for their antioxidant activity, along with much less studied CeF₃ nanoparticles, for their radioprotective potential. In addition, both CeO₂ and CeF₃ nanoparticles improve planarian head blastema regeneration after ionizing irradiation by enhancing blastema growth, increasing the number of mitoses and neoblasts’ survival, and modulating the expression of genes responsible for the proliferation and differentiation of neoblasts. The CeO₂ nanoparticles’ action stems directly from their redox activity as ROS scavengers, while the CeF₃ nanoparticles’ action is mediated by overexpression of “wound-induced genes” and neoblast- and stem cell-regulating genes. Full article

(This article belongs to the Special Issue Advances in Radiation Toxicity)

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20 pages, 1686 KiB

Open AccessArticle

DNA Methylation Alterations in Fractionally Irradiated Rats and Breast Cancer Patients Receiving Radiotherapy

by Magy Sallam, Mohamed Mysara, Mohammed Abderrafi Benotmane, Radia Tamarat, Susana Constantino Rosa Santos, Anne P. G. Crijns, Daan Spoor, Filip Van Nieuwerburgh, Dieter Deforce, Sarah Baatout, Pieter-Jan Guns, An Aerts and Raghda Ramadan

Int. J. Mol. Sci. 2022, 23(24), 16214; https://doi.org/10.3390/ijms232416214 - 19 Dec 2022

Cited by 4 | Viewed by 2088 | Correction

Abstract

Radiation-Induced CardioVascular Disease (RICVD) is an important concern in thoracic radiotherapy with complex underlying pathophysiology. Recently, we proposed DNA methylation as a possible mechanism contributing to RICVD. The current study investigates DNA methylation in heart-irradiated rats and radiotherapy-treated breast cancer (BC) patients. Rats received fractionated whole heart X-irradiation (0, 0.92, 6.9 and 27.6 Gy total doses) and blood was collected after 1.5, 3, 7 and 12 months. Global and gene-specific methylation of the samples were evaluated; and gene expression of selected differentially methylated regions (DMRs) was validated in rat and BC patient blood. In rats receiving an absorbed dose of 27.6 Gy, DNA methylation alterations were detected up to 7 months with differential expression of cardiac-relevant DMRs. Of those, SLMAP showed increased expression at 1.5 months, which correlated with hypomethylation. Furthermore, E2F6 inversely correlated with a decreased global longitudinal strain. In BC patients, E2F6 and SLMAP exhibited differential expression directly and 6 months after radiotherapy, respectively. This study describes a systemic radiation fingerprint at the DNA methylation level, elucidating a possible association of DNA methylation to RICVD pathophysiology, to be validated in future mechanistic studies. Full article

(This article belongs to the Special Issue Advances in Radiation Toxicity)

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18 pages, 4225 KiB

Open AccessArticle

Low-Dose Radiation Affects Cardiovascular Disease Risk in Human Aortic Endothelial Cells by Altering Gene Expression under Normal and Diabetic Conditions

by Soo-Ho Lee, Ye Ji Jeong, Jeongwoo Park, Hyun-Yong Kim, Yeonghoon Son, Kwang Seok Kim and Hae-June Lee

Int. J. Mol. Sci. 2022, 23(15), 8577; https://doi.org/10.3390/ijms23158577 - 2 Aug 2022

Cited by 3 | Viewed by 2145

Abstract

High doses of ionizing radiation can cause cardiovascular diseases (CVDs); however, the effects of <100 mGy radiation on CVD remain underreported. Endothelial cells (ECs) play major roles in cardiovascular health and disease, and their function is reduced by stimuli such as chronic disease, metabolic disorders, and smoking. However, whether exposure to low-dose radiation results in the disruption of similar molecular mechanisms in ECs under diabetic and non-diabetic states remains largely unknown; we aimed to address this gap in knowledge through the molecular and functional characterization of primary human aortic endothelial cells (HAECs) derived from patients with type 2 diabetes (T2D-HAECs) and normal HAECs in response to low-dose radiation. To address these limitations, we performed RNA sequencing on HAECs and T2D-HAECs following exposure to 100 mGy of ionizing radiation and examined the transcriptome changes associated with the low-dose radiation. Compared with that in the non-irradiation group, low-dose irradiation induced 243 differentially expressed genes (DEGs) (133 down-regulated and 110 up-regulated) in HAECs and 378 DEGs (195 down-regulated and 183 up-regulated) in T2D-HAECs. We also discovered a significant association between the DEGs and the interferon (IFN)-I signaling pathway, which is associated with CVD by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein–protein network analysis, and module analysis. Our findings demonstrate the potential impact of low-dose radiation on EC functions that are related to the risk of CVD. Full article

(This article belongs to the Special Issue Advances in Radiation Toxicity)

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17 pages, 2094 KiB

Open AccessCommunication

Hypersensitivity and Induced Radioresistance in Chinese Hamster Cells Exposed to Radiations with Different LET Values

by Ekaterina Koryakina, Vladimir I. Potetnya, Marina Troshina, Raisa Baykuzina, Sergey Koryakin, Anatoliy Lychagin, Aleksei Solovev, Vyacheslav Saburov, Vladimir Pikalov, Petr Shegay, Sergey Ivanov and Andrey Kaprin

Int. J. Mol. Sci. 2022, 23(12), 6765; https://doi.org/10.3390/ijms23126765 - 17 Jun 2022

Cited by 1 | Viewed by 1349

Abstract

We study the impact of radiation LET on manifestation of HRS/IRR response in Chinese hamster cells ovary cells exposed to radiations used in radiotherapy. Earlier we have investigated this response to carbon ions (455 MeV/amu) in the pristine Bragg curve plateau and behind the Bragg peak, ⁶⁰Co γ-rays, and 14.5 MeV neutrons. Now we present results of cytogenetic metaphase analysis in plateau-phase CHO-K1 cells irradiated with scanning beam protons (83 MeV) at doses < 1 Gy and additional data for 14.5 MeV neutrons. Dose curves for frequency of total chromosome aberrations (CA, protons), paired fragments (protons, neutrons), aberrant cells (neutrons) had typical HRS/IRR structure: HRS region (up to 0.1 and 0.15 Gy), IRR region (0.1–0.6 Gy and 0.15–0.35 Gy) for protons and neutrons, respectively, and regular dose dependence. Taken together with previous results, the data show that LET increase shifts the HRS upper border (from 0.08–0.1 Gy for γ-rays, protons and plateau carbons to 0.12–0.15 Gy for “tail” carbons and neutrons). The IRR regions shortens (0.52–0.4 γ-rays and protons, 0.25 plateau carbons, 0.2 Gy “tail” carbons and neutrons). CA level of IRR increases by 1.5–2.5 times for carbons as compared to γ-rays and protons. Outside HRS/IRR the yield of CA also enhanced with LET increase. The results obtained for different LET radiations suggest that CHO-K1 cells with G1-like CA manifested the general feature of the HRS/IRR phenomena. Full article

(This article belongs to the Special Issue Advances in Radiation Toxicity)

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18 pages, 4129 KiB

Open AccessArticle

The Effect of Low-Energy Laser-Driven Ultrashort Pulsed Electron Beam Irradiation on Erythropoiesis and Oxidative Stress in Rats

by Gohar Tsakanova, Aida Avetisyan, Elena Karalova, Liana Abroyan, Lina Hakobyan, Anna Semerjyan, Naira Karalyan, Elina Arakelova, Violetta Ayvazyan, Lusine Matevosyan, Arpine Navasardyan, Anna Ayvazyan, Hakob Davtyan, Bagrat Grigoryan, Arsen Arakelyan and Zaven Karalyan

Int. J. Mol. Sci. 2022, 23(12), 6692; https://doi.org/10.3390/ijms23126692 - 15 Jun 2022

Viewed by 1946

Abstract

Anemia is a commonly observed consequence of whole-body exposure to a dose of X-ray or gamma irradiation of the order of the mean lethal dose in mammals, and it is an important factor for the determination of the survival of animals. The aim of this study was to unravel the effect of laser-driven ultrashort pulsed electron beam (UPEB) irradiation on the process of erythropoiesis and the redox state in the organism. Wistar rats were exposed to laser-driven UPEB irradiation, after which the level of oxidative stress and the activities of different antioxidant enzymes, as well as blood smears, bone marrow imprints and sections, erythroblastic islets, hemoglobin and hematocrit, hepatic iron, DNA, and erythropoietin levels, were assessed on the 1st, 3rd, 7th, 14th, and 28th days after irradiation. Despite the fact that laser-driven UPEB irradiation requires quite low doses and repetition rates to achieve the LD₅₀ in rats, our findings suggest that whole-body exposure with this new type of irradiation causes relatively mild anemia in rats, with subsequent fast recovery up to the 28th day. Moreover, this novel type of irradiation causes highly intense processes of oxidative stress, which, despite being relatively extinguished, did not reach the physiologically stable level even at the 28th day after irradiation due to the violations in the antioxidant system of the organism. Full article

(This article belongs to the Special Issue Advances in Radiation Toxicity)

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12 pages, 4544 KiB

Open AccessArticle

2-Methoxyestradiol Inhibits Radiation-Induced Skin Injuries

by Ji-Hee Kim, Jae-Kyung Nam, A-Ram Kim, Min-Sik Park, Hae-June Lee, Joonho Park, Joon Kim and Yoon-Jin Lee

Int. J. Mol. Sci. 2022, 23(8), 4171; https://doi.org/10.3390/ijms23084171 - 10 Apr 2022

Cited by 5 | Viewed by 2418

Abstract

Radiation-induced skin injury (RISI) is a main side effect of radiotherapy for cancer patients, with vascular damage being a common pathogenesis of acute and chronic RISI. Despite the severity of RISI, there are few treatments for it that are in clinical use. 2-Methoxyestradiol (2-ME) has been reported to regulate the radiation-induced vascular endothelial-to-mesenchymal transition. Thus, we investigated 2-ME as a potent anti-cancer and hypoxia-inducible factor 1 alpha (HIF-1α) inhibitor drug that prevents RISI by targeting HIF-1α. 2-ME treatment prior to and post irradiation inhibited RISI on the skin of C57/BL6 mice. 2-ME also reduced radiation-induced inflammation, skin thickness, and vascular fibrosis. In particular, post-treatment with 2-ME after irradiation repaired the damaged vessels on the irradiated dermal skin, inhibiting endothelial HIF-1α expression. In addition to the increase in vascular density, post-treatment with 2-ME showed fibrotic changes in residual vessels with SMA⁺CD31⁺ on the irradiated skin. Furthermore, 2-ME significantly inhibited fibrotic changes and accumulated DNA damage in irradiated human dermal microvascular endothelial cells. Therefore, we suggest that 2-ME may be a potent therapeutic agent for RISI. Full article

(This article belongs to the Special Issue Advances in Radiation Toxicity)

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14 pages, 14581 KiB

Open AccessArticle

Exposure to b-LED Light While Exerting Antimicrobial Activity on Gram-Negative and -Positive Bacteria Promotes Transient EMT-like Changes and Growth Arrest in Keratinocytes

by Michela Terri, Nicoletta Mancianti, Flavia Trionfetti, Bruno Casciaro, Valeria de Turris, Giammarco Raponi, Giulio Bontempi, Claudia Montaldo, Alessandro Domenici, Paolo Menè, Maria Luisa Mangoni and Raffaele Strippoli

Int. J. Mol. Sci. 2022, 23(3), 1896; https://doi.org/10.3390/ijms23031896 - 8 Feb 2022

Cited by 2 | Viewed by 2202

Abstract

While blue LED (b-LED) light is increasingly being studied for its cytotoxic activity towards bacteria in therapy of skin-related infections, its effects on eukaryotic cells plasticity are less well characterized. Moreover, since different protocols are often used, comparing the effect of b-LED towards both microorganisms and epithelial surfaces may be difficult. The aim of this study was to analyze, in the same experimental setting, both the bactericidal activity and the effects on human keratinocytes. Exposure to b-LED induced an intense cytocidal activity against Gram-positive (i.e, Staphylococcus aureus) and Gram-negative (i.e., Pseudomonas aeruginosa) bacteria associated with catheter-related infections. Treatment with b-LED of a human keratinocyte cell line induced a transient cell cycle arrest. At the molecular level, exposure to b-LED induced a transient downregulation of Cyclin D1 and an upregulation of p21, but not signs of apoptosis. Interestingly, a transient induction of phosphor-histone γ-H2Ax, which is associated with genotoxic damages, was observed. At the same time, keratinocytes underwent a transient epithelial to mesenchymal transition (EMT)-like phenotype, characterized by E-cadherin downregulation and SNAIL/SLUG induction. As a functional readout of EMT induction, a scratch assay was performed. Surprisingly, b-LED treatment provoked a delay in the scratch closure. In conclusion, we demonstrated that b-LED microbicidal activity is associated with complex responses in keratinocytes that certainly deserve further analysis. Full article

(This article belongs to the Special Issue Advances in Radiation Toxicity)

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Review

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33 pages, 3114 KiB

Open AccessReview

The Damaging Effects of Long UVA (UVA1) Rays: A Major Challenge to Preserve Skin Health and Integrity

by Françoise Bernerd, Thierry Passeron, Isabelle Castiel and Claire Marionnet

Int. J. Mol. Sci. 2022, 23(15), 8243; https://doi.org/10.3390/ijms23158243 - 26 Jul 2022

Cited by 44 | Viewed by 6261

Abstract

Within solar ultraviolet (UV) light, the longest UVA1 wavelengths, with significant and relatively constant levels all year round and large penetration properties, produce effects in all cutaneous layers. Their effects, mediated by numerous endogenous chromophores, primarily involve the generation of reactive oxygen species (ROS). The resulting oxidative stress is the major mode of action of UVA1, responsible for lipid peroxidation, protein carbonylation, DNA lesions and subsequent intracellular signaling cascades. These molecular changes lead to mutations, apoptosis, dermis remodeling, inflammatory reactions and abnormal immune responses. The altered biological functions contribute to clinical consequences such as hyperpigmentation, inflammation, photoimmunosuppression, sun allergies, photoaging and photocancers. Such harmful impacts have also been reported after the use of UVA1 phototherapy or tanning beds. Furthermore, other external aggressors, such as pollutants and visible light (Vis), were shown to induce independent, cumulative and synergistic effects with UVA1 rays. In this review, we synthetize the biological and clinical effects of UVA1 and the complementary effects of UVA1 with pollutants or Vis. The identified deleterious biological impact of UVA1 contributing to clinical consequences, combined with the predominance of UVA1 rays in solar UV radiation, constitute a solid rational for the need for a broad photoprotection, including UVA1 up to 400 nm. Full article

(This article belongs to the Special Issue Advances in Radiation Toxicity)

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