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Advances and Challenges in Biomolecular Radiation Research 2.0
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Advances and Challenges in Biomolecular Radiation Research 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 March 2022) | Viewed by 13548

Special Issue Editor

Prof. Dr. Michael Hausmann

E-Mail Website
Guest Editor
Experimental Biophysics, Kirchhoff-Institute for Physics, University of Heidelberg, Im Neuenheimer Feld 227, 69120 Heidelberg, Germany
Interests: genom-architecture on the micro- and nano-scale during tumor genesis and after ionizing radiation exposure; nano-probes for DNA; DNA patterning; protein arrangements on the nano-scale in cell membranes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Research focused on understanding the complex responses of cells to the radiation-induced damage of functional molecules requires a multidisciplinary approach: investigations based on knowledge from physics, biology, chemistry, medicine, computer science, etc. The Special Issue “Advances and Challenges in Biomolecular Radiation Research” launched in 2018 demonstrated how synergistic multidisciplinary work can improve the state of knowledge in the field of radiation research.

In recent decades, studies of genetic and epigenetic changes in response to radiation exposure have significantly contributed to a better understanding of the machinery of DNA repair, complex protein-interaction pathways, and their inhibition or associated immune reactions. Nevertheless, understanding the mechanisms behind radiosensitivity and resistance is still challenging for radiation research, improvements in radiation protection and (personalized) medical radiation treatment. With upcoming novel techniques in molecular probing and engineering, nanoscience, super-resolution microscopy, high-throughput analyses, and “big data”-based computer modelling, etc., a huge toolbox has become available for further investigating reactions to cellular radiation and responses at the single-cell or even (single) biomolecular level.

After two years of research and further scientific development and improvements, we think that the time has come to start the new Special Issue “Advances and Challenges in Biomolecular Radiation Research II”, in order to continue from the 2018 issue, especially in these pandemic times in which conferences and scientific exchange are restricted. This Special Issue will focus on experimental and theoretical advances in molecular sciences, and on technological challenges and solutions in modern biological radiation research as well as biomolecular approaches towards (personalized) medical diagnosis and treatment. As Guest Editor, I would like to invite scientists working in biomolecular radiation research to submit their recent results to this Special Issue in order to demonstrate the breadth and vitality of this field.

Prof. Dr. Michael Hausmann
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.

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Keywords

  • Biomolecular radiation response
  • Single-cell biodosimetry
  • Novel molecular techniques in radiation research
  • Methodological challenges in radiation research
  • Biomolecular effects of medical radiation treatment
  • Molecular effects in DNA repair
  • Molecular immune responses to radiation
  • Simulation of molecular radiation effects

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Published Papers (4 papers)

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Research

16 pages, 2545 KiB  
Article
Increased Gene Targeting in Hyper-Recombinogenic LymphoBlastoid Cell Lines Leaves Unchanged DSB Processing by Homologous Recombination
by Emil Mladenov, Katja Paul-Konietzko, Veronika Mladenova, Martin Stuschke and George Iliakis
Int. J. Mol. Sci. 2022, 23(16), 9180; https://doi.org/10.3390/ijms23169180 - 16 Aug 2022
Cited by 3 | Viewed by 2318
Abstract
In the cells of higher eukaryotes, sophisticated mechanisms have evolved to repair DNA double-strand breaks (DSBs). Classical nonhomologous end joining (c-NHEJ), homologous recombination (HR), alternative end joining (alt-EJ) and single-strand annealing (SSA) exploit distinct principles to repair DSBs throughout the cell cycle, resulting [...] Read more.
In the cells of higher eukaryotes, sophisticated mechanisms have evolved to repair DNA double-strand breaks (DSBs). Classical nonhomologous end joining (c-NHEJ), homologous recombination (HR), alternative end joining (alt-EJ) and single-strand annealing (SSA) exploit distinct principles to repair DSBs throughout the cell cycle, resulting in repair outcomes of different fidelity. In addition to their functions in DSB repair, the same repair pathways determine how cells integrate foreign DNA or rearrange their genetic information. As a consequence, random integration of DNA fragments is dominant in somatic cells of higher eukaryotes and suppresses integration events at homologous genomic locations, leading to very low gene-targeting efficiencies. However, this response is not universal, and embryonic stem cells display increased targeting efficiency. Additionally, lymphoblastic chicken and human cell lines DT40 and NALM6 show up to a 1000-fold increased gene-targeting efficiency that is successfully harnessed to generate knockouts for a large number of genes. We inquired whether the increased gene-targeting efficiency of DT40 and NALM6 cells is linked to increased rates of HR-mediated DSB repair after exposure to ionizing radiation (IR). We analyzed IR-induced γ-H2AX foci as a marker for the total number of DSBs induced in a cell and RAD51 foci as a marker for the fraction of those DSBs undergoing repair by HR. We also evaluated RPA accretion on chromatin as evidence for ongoing DNA end resection, an important initial step for all pathways of DSB repair except c-NHEJ. We finally employed the DR-GFP reporter assay to evaluate DSB repair by HR in DT40 cells. Collectively, the results obtained, unexpectedly show that DT40 and NALM6 cells utilized HR for DSB repair at levels very similar to those of other somatic cells. These observations uncouple gene-targeting efficiency from HR contribution to DSB repair and suggest the function of additional mechanisms increasing gene-targeting efficiency. Indeed, our results show that analysis of the contribution of HR to DSB repair may not be used as a proxy for gene-targeting efficiency. Full article
(This article belongs to the Special Issue Advances and Challenges in Biomolecular Radiation Research 2.0)
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19 pages, 4918 KiB  
Article
Low-Energy Laser-Driven Ultrashort Pulsed Electron Beam Irradiation-Induced Immune Response in Rats
by Gohar Tsakanova, Nelly Babayan, Elena Karalova, Lina Hakobyan, Liana Abroyan, Aida Avetisyan, Hranush Avagyan, Sona Hakobyan, Arpine Poghosyan, Bagrat Baghdasaryan, Elina Arakelova, Violetta Ayvazyan, Lusine Matevosyan, Arpine Navasardyan, Hakob Davtyan, Lilit Apresyan, Arsham Yeremyan, Rouben Aroutiounian, Andreyan N. Osipov, Bagrat Grigoryan and Zaven Karalyanadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2021, 22(21), 11525; https://doi.org/10.3390/ijms222111525 - 26 Oct 2021
Cited by 7 | Viewed by 3215
Abstract
The development of new laser-driven electron linear accelerators, providing unique ultrashort pulsed electron beams (UPEBs) with low repetition rates, opens new opportunities for radiotherapy and new fronts for radiobiological research in general. Considering the growing interest in the application of UPEBs in radiation [...] Read more.
The development of new laser-driven electron linear accelerators, providing unique ultrashort pulsed electron beams (UPEBs) with low repetition rates, opens new opportunities for radiotherapy and new fronts for radiobiological research in general. Considering the growing interest in the application of UPEBs in radiation biology and medicine, the aim of this study was to reveal the changes in immune system in response to low-energy laser-driven UPEB whole-body irradiation in rodents. Forty male albino Wistar rats were exposed to laser-driven UPEB irradiation, after which different immunological parameters were studied on the 1st, 3rd, 7th, 14th, and 28th day after irradiation. According to the results, this type of irradiation induces alterations in the rat immune system, particularly by increasing the production of pro- and anti-inflammatory cytokines and elevating the DNA damage rate. Moreover, such an immune response reaches its maximal levels on the third day after laser-driven UPEB whole-body irradiation, showing partial recovery on subsequent days with a total recovery on the 28th day. The results of this study provide valuable insight into the effect of laser-driven UPEB whole-body irradiation on the immune system of the animals and support further animal experiments on the role of this novel type of irradiation. Full article
(This article belongs to the Special Issue Advances and Challenges in Biomolecular Radiation Research 2.0)
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14 pages, 39962 KiB  
Article
Focused Ion Microbeam Irradiation Induces Clustering of DNA Double-Strand Breaks in Heterochromatin Visualized by Nanoscale-Resolution Electron Microscopy
by Yvonne Lorat, Judith Reindl, Anna Isermann, Christian Rübe, Anna A. Friedl and Claudia E. Rübe
Int. J. Mol. Sci. 2021, 22(14), 7638; https://doi.org/10.3390/ijms22147638 - 16 Jul 2021
Cited by 15 | Viewed by 3296
Abstract
Background: Charged-particle radiotherapy is an emerging treatment modality for radioresistant tumors. The enhanced effectiveness of high-energy particles (such as heavy ions) has been related to the spatial clustering of DNA lesions due to highly localized energy deposition. Here, DNA damage patterns induced by [...] Read more.
Background: Charged-particle radiotherapy is an emerging treatment modality for radioresistant tumors. The enhanced effectiveness of high-energy particles (such as heavy ions) has been related to the spatial clustering of DNA lesions due to highly localized energy deposition. Here, DNA damage patterns induced by single and multiple carbon ions were analyzed in the nuclear chromatin environment by different high-resolution microscopy approaches. Material and Methods: Using the heavy-ion microbeam SNAKE, fibroblast monolayers were irradiated with defined numbers of carbon ions (1/10/100 ions per pulse, ipp) focused to micrometer-sized stripes or spots. Radiation-induced lesions were visualized as DNA damage foci (γH2AX, 53BP1) by conventional fluorescence and stimulated emission depletion (STED) microscopy. At micro- and nanoscale level, DNA double-strand breaks (DSBs) were visualized within their chromatin context by labeling the Ku heterodimer. Single and clustered pKu70-labeled DSBs were quantified in euchromatic and heterochromatic regions at 0.1 h, 5 h and 24 h post-IR by transmission electron microscopy (TEM). Results: Increasing numbers of carbon ions per beam spot enhanced spatial clustering of DNA lesions and increased damage complexity with two or more DSBs in close proximity. This effect was detectable in euchromatin, but was much more pronounced in heterochromatin. Analyzing the dynamics of damage processing, our findings indicate that euchromatic DSBs were processed efficiently and repaired in a timely manner. In heterochromatin, by contrast, the number of clustered DSBs continuously increased further over the first hours following IR exposure, indicating the challenging task for the cell to process highly clustered DSBs appropriately. Conclusion: Increasing numbers of carbon ions applied to sub-nuclear chromatin regions enhanced the spatial clustering of DSBs and increased damage complexity, this being more pronounced in heterochromatic regions. Inefficient processing of clustered DSBs may explain the enhanced therapeutic efficacy of particle-based radiotherapy in cancer treatment. Full article
(This article belongs to the Special Issue Advances and Challenges in Biomolecular Radiation Research 2.0)
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14 pages, 2935 KiB  
Article
UVB Inhibits Proliferation, Cell Cycle and Induces Apoptosis via p53, E2F1 and Microtubules System in Cervical Cancer Cell Lines
by Angelica Judith Granados-López, Eduardo Manzanares-Acuña, Yamilé López-Hernández, Julio Enrique Castañeda-Delgado, Ixamail Fraire-Soto, Claudia Araceli Reyes-Estrada, Rosalinda Gutiérrez-Hernández and Jesús Adrián López
Int. J. Mol. Sci. 2021, 22(10), 5197; https://doi.org/10.3390/ijms22105197 - 14 May 2021
Cited by 15 | Viewed by 3744
Abstract
Ultraviolet (UV) exposure has been linked to skin damage and carcinogenesis, but recently UVB has been proposed as a therapeutic approach for cancer. Herein, we investigated the cellular and molecular effects of UVB in immortal and tumorigenic HPV positive and negative cells. Cells [...] Read more.
Ultraviolet (UV) exposure has been linked to skin damage and carcinogenesis, but recently UVB has been proposed as a therapeutic approach for cancer. Herein, we investigated the cellular and molecular effects of UVB in immortal and tumorigenic HPV positive and negative cells. Cells were irradiated with 220.5 to 1102.5 J/m2 of UVB and cell proliferation was evaluated by crystal violet, while cell cycle arrest and apoptosis analysis were performed through flow cytometry. UVB effect on cells was recorded at 661.5 J/m2 and it was exacerbated at 1102.5 J/m2. All cell lines were affected by proliferation inhibition, cell cycle ablation and apoptosis induction, with different degrees depending on tumorigenesis level or HPV type. Analysis of the well-known UV-responsive p53, E2F1 and microtubules system proteins was performed in SiHa cells in response to UVB through Western-blotting assays. E2F1 and the Microtubule-associated protein 2 (MAP2) expression decrease correlated with cellular processes alteration while p53 and Microtubule-associated Protein 1S (MAP1S) expression switch was observed since 882 J/m2, suggesting they were required under more severe cellular damage. However, expression transition of α-Tubulin3C and β-Tubulin was abruptly noticed until 1102.5 J/m2 and particularly, γ-Tubulin protein expression remained without alteration. This study provides insights into the effect of UVB in cervical cancer cell lines. Full article
(This article belongs to the Special Issue Advances and Challenges in Biomolecular Radiation Research 2.0)
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