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The Effect of Ionizing Radiation on Human Cells
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The Effect of Ionizing Radiation on Human Cells

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

Deadline for manuscript submissions: closed (15 July 2024) | Viewed by 6940

Special Issue Editors

Dr. Judith Reindl

E-Mail Website
Guest Editor
Faculty of Aerospace Engineering, Institute of Applied Physics and Measurement Technology (LRT 2), Universität der Bundeswehr München, D-85577 Neubiberg, Germany
Interests: DNA; radiation biology
Dr. Omid Azimzadeh

E-Mail
Guest Editor
Section of Radiation Biology, Federal Office of Radiation Protection (BfS), 85764 Nauenberg, Germany
Interests: radiation omics; radiation biology; normal tissue response; metabolism; PPAR; cell interaction; cancer therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ionizing radiation is a critical area of study, as it has widespread implications for various fields, including medical science, environmental health, and radiation therapy. This special issue will provide a platform for researchers, scientists, and experts to share their findings and contribute to our understanding of the biological responses to ionizing radiation. It aims to gather cutting-edge research and insights into the impact of ionizing radiation on human cells, shedding light on its mechanisms, consequences, and potential applications.

The special issue invites original research articles, reviews, and perspectives that address diverse aspects related to ionizing radiation, such as:

  1. Mechanisms of DNA damage and repair in response to ionizing radiation.
  2. Cellular and molecular responses to ionizing radiation exposure.
  3. Radiobiology and radiation therapy strategies for cancer treatment.
  4. Molecular mechanisms of long-term effects of ionizing radiation on human health.
  5. Novel techniques and technologies for assessing radiation-induced cellular and molecular responses.
  6. Protection and mitigation strategies based on the molecular effects of radiation.

We invite researchers to submit their original work to this special issue. Manuscripts will undergo a rigorous peer-review process, ensuring the publication of high-quality research.

We encourage scientists and experts in the field of ionizing radiation to contribute to this special issue and help shape the future of research in this crucial area.

Together, let us explore the profound effects of ionizing radiation on human cells and molecules and pave the way for advancements in radiation biology and its applications.

Dr. Judith Reindl
Dr. Omid Azimzadeh
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 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

  • DNA repair
  • ionizing radiation
  • radiation induced cellular and molecular response
  • molecular mechanisms of long-term effects of radiation
  • radiobiology
  • cancer treatment

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Published Papers (6 papers)

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Research

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22 pages, 9852 KiB  
Article
X-ray Radiotherapy Impacts Cardiac Dysfunction by Modulating the Sympathetic Nervous System and Calcium Transients
by Justyne Feat-Vetel, Nadine Suffee, Florence Bachelot, Morgane Dos Santos, Nathalie Mougenot, Elise Delage, Florian Saliou, Sabrina Martin, Isabelle Brunet, Pierre Sicard and Virginie Monceau
Int. J. Mol. Sci. 2024, 25(17), 9483; https://doi.org/10.3390/ijms25179483 - 31 Aug 2024
Viewed by 296
Abstract
Recent epidemiological studies have shown that patients with right-sided breast cancer (RBC) treated with X-ray irradiation (IR) are more susceptible to developing cardiovascular diseases, such as arrhythmias, atrial fibrillation, and conduction disturbances after radiotherapy (RT). Our aim was to investigate the mechanisms induced [...] Read more.
Recent epidemiological studies have shown that patients with right-sided breast cancer (RBC) treated with X-ray irradiation (IR) are more susceptible to developing cardiovascular diseases, such as arrhythmias, atrial fibrillation, and conduction disturbances after radiotherapy (RT). Our aim was to investigate the mechanisms induced by low to moderate doses of IR and to evaluate changes in the cardiac sympathetic nervous system (CSNS), atrial remodeling, and calcium homeostasis involved in cardiac rhythm. To mimic the RT of the RBC, female C57Bl/6J mice were exposed to X-ray doses ranging from 0.25 to 2 Gy targeting 40% of the top of the heart. At 60 weeks after RI, Doppler ultrasound showed a significant reduction in myocardial strain, ejection fraction, and atrial function, with a significant accumulation of fibrosis in the epicardial layer and apoptosis at 0.5 mGy. Calcium transient protein expression levels, such as RYR2, NAK, Kir2.1, and SERCA2a, increased in the atrium only at 0.5 Gy and 2 Gy at 24 h, and persisted over time. Interestingly, 3D imaging of the cleaned hearts showed an early reduction of CSNS spines and dendrites in the ventricles and a late reorientation of nerve fibers, combined with a decrease in SEMA3a expression levels. Our results showed that local heart IR from 0.25 Gy induced late cardiac and atrial dysfunction and fibrosis development. After IR, ventricular CSNS and calcium transient protein expression levels were rearranged, which affected cardiac contractility. The results are very promising in terms of identifying pro-arrhythmic mechanisms and preventing arrhythmias during RT treatment in patients with RBC. Full article
(This article belongs to the Special Issue The Effect of Ionizing Radiation on Human Cells)
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28 pages, 3844 KiB  
Article
The Importance of Anharmonicity and Solvent Effects on the OH Radical Attack on Nucleobases
by Anna Thorn Ekstrøm, Vera Staun Hansen and Stephan P. A. Sauer
Int. J. Mol. Sci. 2024, 25(6), 3118; https://doi.org/10.3390/ijms25063118 - 8 Mar 2024
Viewed by 1506
Abstract
Previous theoretical investigations of the reactions between an OH radical and a nucleobase have stated the most important pathways to be the C5-C6 addition for pyrimidines and the C8 addition for purines. Furthermore, the abstraction of a methyl hydrogen from thymine has also [...] Read more.
Previous theoretical investigations of the reactions between an OH radical and a nucleobase have stated the most important pathways to be the C5-C6 addition for pyrimidines and the C8 addition for purines. Furthermore, the abstraction of a methyl hydrogen from thymine has also been proven an important pathway. The conclusions were based solely on gas-phase calculations and harmonic vibrational frequencies. In this paper, we supplement the calculations by applying solvent corrections through the polarizable continuum model (PCM) solvent model and applying anharmonicity in order to determine the importance of anharmonicity and solvent effects. Density functional theory (DFT) at the ωB97-D/6-311++G(2df,2pd) level with the Eckart tunneling correction is used. The total reaction rate constants are found to be 1.48 ×10−13 cm3 molecules−1s−1 for adenine, 1.02 ×10−11 cm3 molecules−1s−1 for guanine, 5.52 ×10−13 cm3 molecules−1s−1 for thymine, 1.47 ×10−13 cm3 molecules−1s−1 for cytosine and 7.59 ×10−14 cm3 molecules−1s−1 for uracil. These rates are found to be approximately two orders of magnitude larger than experimental values. We find that the tendencies observed for preferred pathways for reactions calculated in a solvent are comparable to the preferred pathways for reactions calculated in gas phase. We conclude that applying a solvent has a larger impact on more parameters compared to the inclusion of anharmonicity. For some reactions the inclusion of anharmonicity has no effect, whereas for others it does impact the energetics. Full article
(This article belongs to the Special Issue The Effect of Ionizing Radiation on Human Cells)
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13 pages, 6246 KiB  
Article
Chromatin Organization after High-LET Irradiation Revealed by Super-Resolution STED Microscopy
by Benjamin Schwarz, Nicole Matejka, Sarah Rudigkeit, Matthias Sammer and Judith Reindl
Int. J. Mol. Sci. 2024, 25(1), 628; https://doi.org/10.3390/ijms25010628 - 3 Jan 2024
Viewed by 1409
Abstract
Ion-radiation-induced DNA double-strand breaks can lead to severe cellular damage ranging from mutations up to direct cell death. The interplay between the chromatin surrounding the damage and the proteins responsible for damage recognition and repair determines the efficiency and outcome of DNA repair. [...] Read more.
Ion-radiation-induced DNA double-strand breaks can lead to severe cellular damage ranging from mutations up to direct cell death. The interplay between the chromatin surrounding the damage and the proteins responsible for damage recognition and repair determines the efficiency and outcome of DNA repair. The chromatin is organized in three major functional compartments throughout the interphase: the chromatin territories, the interchromatin compartment, and the perichromatin lying in between. In this study, we perform correlation analysis using super-resolution STED images of chromatin; splicing factor SC35, as an interchromatin marker; and the DNA repair factors 53BP1, Rad51, and γH2AX in carbon-ion-irradiated human HeLa cells. Chromatin and interchromatin overlap only in protruding chromatin branches, which is the same for the correlation between chromatin and 53BP1. In contrast, between interchromatin and 53BP1, a gap of (270 ± 40) nm is visible. Rad51 shows overlap with decondensed euchromatic regions located at the borders of condensed heterochromatin with further correlation with γH2AX. We conclude that the DNA damage is repaired in decondensed DNA loops in the perichromatin, located in the periphery of the DNA-dense chromatin compartments containing the heterochromatin. Proteins like γH2AX and 53BP1 serve as supporters of the chromatin structure. Full article
(This article belongs to the Special Issue The Effect of Ionizing Radiation on Human Cells)
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10 pages, 2598 KiB  
Article
Radiobiological Assessment of Targeted Radionuclide Therapy with [177Lu]Lu-PSMA-I&T in 2D vs. 3D Cell Culture Models
by Julia Raitanen, Bernadette Barta, Hermann Fuchs, Marcus Hacker, Theresa Balber, Dietmar Georg and Markus Mitterhauser
Int. J. Mol. Sci. 2023, 24(23), 17015; https://doi.org/10.3390/ijms242317015 - 30 Nov 2023
Cited by 2 | Viewed by 1178
Abstract
In vitro therapeutic efficacy studies are commonly conducted in cell monolayers. However, three-dimensional (3D) tumor spheroids are known to better represent in vivo tumors. This study used [177Lu]Lu-PSMA-I&T, an already clinically applied radiopharmaceutical for targeted radionuclide therapy against metastatic castrate-resistant prostate [...] Read more.
In vitro therapeutic efficacy studies are commonly conducted in cell monolayers. However, three-dimensional (3D) tumor spheroids are known to better represent in vivo tumors. This study used [177Lu]Lu-PSMA-I&T, an already clinically applied radiopharmaceutical for targeted radionuclide therapy against metastatic castrate-resistant prostate cancer, to demonstrate the differences in the radiobiological response between 2D and 3D cell culture models of the prostate cancer cell lines PC-3 (PSMA negative) and LNCaP (PSMA positive). After assessing the target expression in both models via Western Blot, cell viability, reproductive ability, and growth inhibition were assessed. To investigate the geometric effects on dosimetry for the 2D vs. 3D models, Monte Carlo simulations were performed. Our results showed that PSMA expression in LNCaP spheroids was highly preserved, and target specificity was shown in both models. In monolayers of LNCaP, no short-term (48 h after treatment), but only long-term (14 days after treatment) radiobiological effects were evident, showing decreased viability and reproductive ability with the increasing activity. Further, LNCaP spheroid growth was inhibited with the increasing activity. Overall, treatment efficacy was higher in LNCaP spheroids compared to monolayers, which can be explained by the difference in the resulting dose, among others. Full article
(This article belongs to the Special Issue The Effect of Ionizing Radiation on Human Cells)
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Review

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27 pages, 1318 KiB  
Review
Impact of Ionizing Radiation Exposure on Placental Function and Implications for Fetal Programming
by Cameron Hourtovenko, Shayen Sreetharan, Sujeenthar Tharmalingam and T. C. Tai
Int. J. Mol. Sci. 2024, 25(18), 9862; https://doi.org/10.3390/ijms25189862 - 12 Sep 2024
Abstract
Accidental exposure to high-dose radiation while pregnant has shown significant negative effects on the developing fetus. One fetal organ which has been studied is the placenta. The placenta performs all essential functions for fetal development, including nutrition, respiration, waste excretion, endocrine communication, and [...] Read more.
Accidental exposure to high-dose radiation while pregnant has shown significant negative effects on the developing fetus. One fetal organ which has been studied is the placenta. The placenta performs all essential functions for fetal development, including nutrition, respiration, waste excretion, endocrine communication, and immunological functions. Improper placental development can lead to complications during pregnancy, as well as the occurrence of intrauterine growth-restricted (IUGR) offspring. IUGR is one of the leading indicators of fetal programming, classified as an improper uterine environment leading to the predisposition of diseases within the offspring. With numerous studies examining fetal programming, there remains a significant gap in understanding the placenta’s role in irradiation-induced fetal programming. This review aims to synthesize current knowledge on how irradiation affects placental function to guide future research directions. This review provides a comprehensive overview of placental biology, including its development, structure, and function, and summarizes the placenta’s role in fetal programming, with a focus on the impact of radiation on placental biology. Taken together, this review demonstrates that fetal radiation exposure causes placental degradation and immune function dysregulation. Given the placenta’s crucial role in fetal development, understanding its impact on irradiation-induced IUGR is essential. Full article
(This article belongs to the Special Issue The Effect of Ionizing Radiation on Human Cells)
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13 pages, 1465 KiB  
Review
RNA N6-Methyladenosine Modification in DNA Damage Response and Cancer Radiotherapy
by Cui Wang, Shibo Yao, Tinghui Zhang, Xiaoya Sun, Chenjun Bai and Pingkun Zhou
Int. J. Mol. Sci. 2024, 25(5), 2597; https://doi.org/10.3390/ijms25052597 - 23 Feb 2024
Viewed by 1516
Abstract
The N6-methyladenosine (M6A) modification is the most common internal chemical modification of RNA molecules in eukaryotes. This modification can affect mRNA metabolism, regulate RNA transcription, nuclear export, splicing, degradation, and translation, and significantly impact various aspects of physiology and pathobiology. Radiotherapy is the [...] Read more.
The N6-methyladenosine (M6A) modification is the most common internal chemical modification of RNA molecules in eukaryotes. This modification can affect mRNA metabolism, regulate RNA transcription, nuclear export, splicing, degradation, and translation, and significantly impact various aspects of physiology and pathobiology. Radiotherapy is the most common method of tumor treatment. Different intrinsic cellular mechanisms affect the response of cells to ionizing radiation (IR) and the effectiveness of cancer radiotherapy. In this review, we summarize and discuss recent advances in understanding the roles and mechanisms of RNA M6A methylation in cellular responses to radiation-induced DNA damage and in determining the outcomes of cancer radiotherapy. Insights into RNA M6A methylation in radiation biology may facilitate the improvement of therapeutic strategies for cancer radiotherapy and radioprotection of normal tissues. Full article
(This article belongs to the Special Issue The Effect of Ionizing Radiation on Human Cells)
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