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Radiation Damage in Biomolecules and Cells 3.0
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Radiation Damage in Biomolecules and Cells 3.0

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 (31 March 2023) | Viewed by 8239

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
Special Issues, Collections and Topics in MDPI journals
Dr. Mario Pietro Carante

E-Mail Website
Guest Editor
1. Istituto Nazionale di Fisica Nucleare – Sezione di Pavia, Pavia, Italy
2. Physics Department, University of Pavia, Pavia, Italy
Interests: ionizing radiation; radiobiology; hadron therapy; nuclear physics
Special Issues, Collections and Topics in MDPI journals

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 3.0” 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 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
  • DNA damage
  • chromosome aberrations
  • cell death
  • hadron therapy
  • radiation protection
  • biophysical models
  • computational radiobiology

Published Papers (5 papers)

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Research

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16 pages, 2472 KiB  
Article
The Influence of Spirodi(Iminohydantoin) on Charge Transfer through ds-DNA Containing 8-OXO-dG: A Theoretical Approach
by Boleslaw T. Karwowski
Int. J. Mol. Sci. 2023, 24(10), 8570; https://doi.org/10.3390/ijms24108570 - 10 May 2023
Viewed by 1130
Abstract
Genetic information stored in a DNA base sequence is continuously exposed to harmful factors. It has been determined that 9 × 104 different DNA damage events occur in a single human cell every 24 h. Of these, 7,8-dihydro-8-oxo-guanosine (OXOG) is [...] Read more.
Genetic information stored in a DNA base sequence is continuously exposed to harmful factors. It has been determined that 9 × 104 different DNA damage events occur in a single human cell every 24 h. Of these, 7,8-dihydro-8-oxo-guanosine (OXOG) is one of the most abundant and can undergo further transformations towards spirodi(iminohydantoin) (Sp). Sp is highly mutagenic in comparison to its precursor if not repaired. In this paper, the influence of both Sp diastereomers 4R and 4S as well as their anti and syn conformers on charge transfer through the double helix was taken into theoretical consideration. In addition, the electronic properties of four modelled double-stranded oligonucleotides (ds-oligos) were also discussed, i.e., d[A1Sp2A3oxoG4A5] * [T5C4T3C2T1]. Throughout the study, the M06—2X/6—31++G** level theory was used. Solvent–solute non-equilibrated and equilibrated interactions were also considered. The subsequent results elucidated that the 7,8-dihydro-8-oxo-guanosine:cytidine (OXOGC) base pair is the settled point of a migrated radical cation in each of the discussed cases, due to its low adiabatic ionization potential, i.e., ~5.55 [eV]. The opposite was noted for excess electron transfer through ds-oligos containing anti (R)-Sp or anti (S)-Sp. The radical anion was found on the OXOGC moiety, whereas in the presence of syn (S)-Sp or syn (R)-Sp, an excess electron was found on the distal A1T5 or A5T1 base pair, respectively. Furthermore, a spatial geometry analysis of the discussed ds-oligos revealed that the presence of syn (R)-Sp in the ds-oligo caused only a slight deformation to the double helix, while syn (S)-Sp formed an almost ideal base pair with a complementary dC. The above results are in strong agreement with the final charge transfer rate constant, as calculated according to Marcus’ theory. In conclusion, DNA damage such as spirodi(iminohydantoin), especially when becoming part of clustered DNA damage, can affect the effectiveness of other lesion recognition and repair processes. This can lead to the acceleration of undesired and deleterious processes such as carcinogenesis or aging. However, in terms of anticancer radio-/chemo- or combined therapy, the slowing down of the repair machinery can result in increased effectiveness. With this in mind, the influence of clustered damage on charge transfer and its subsequent effect on single-damage recognition by glycosylases justifies future investigation. Full article
(This article belongs to the Special Issue Radiation Damage in Biomolecules and Cells 3.0)
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15 pages, 1987 KiB  
Article
Characterization of Intrinsic Radiation Sensitivity in a Diverse Panel of Normal, Cancerous and CRISPR-Modified Cell Lines
by Francisco D. C. Guerra Liberal and Stephen J. McMahon
Int. J. Mol. Sci. 2023, 24(9), 7861; https://doi.org/10.3390/ijms24097861 - 26 Apr 2023
Cited by 2 | Viewed by 1697
Abstract
Intrinsic radiosensitivity is a major determinant of radiation response. Despite the extensive amount of radiobiological data available, variability among different studies makes it very difficult to produce high-quality radiosensitivity biomarkers or predictive models. Here, we characterize a panel of 27 human cell lines, [...] Read more.
Intrinsic radiosensitivity is a major determinant of radiation response. Despite the extensive amount of radiobiological data available, variability among different studies makes it very difficult to produce high-quality radiosensitivity biomarkers or predictive models. Here, we characterize a panel of 27 human cell lines, including those derived from lung cancer, prostate cancer, and normal tissues. In addition, we used CRISPR-Cas9 to generate a panel of lines with known DNA repair defects. These cells were characterised by measuring a range of biological features, including the induction and repair of DNA double-strand breaks (DSBs), cell cycle distribution, ploidy, and clonogenic survival following X-ray irradiation. These results offer a robust dataset without inter-experimental variabilities for model development. In addition, we used these results to explore correlations between potential determinants of radiosensitivity. There was a wide variation in the intrinsic radiosensitivity of cell lines, with cell line Mean Inactivation Doses (MID) ranging from 1.3 to 3.4 Gy for cell lines, and as low as 0.65 Gy in Lig4−/− cells. Similar substantial variability was seen in the other parameters, including baseline DNA damage, plating efficiency, and ploidy. In the CRISPR-modified cell lines, residual DSBs were good predictors of cell survival (R2 = 0.78, p = 0.009), as were induced levels of DSBs (R2 = 0.61, p = 0.01). However, amongst the normal and cancerous cells, none of the measured parameters correlated strongly with MID (R2 < 0.45), and the only metrics with statistically significant associations are plating efficiency (R2 = 0.31, p = 0.01) and percentage of cell in S phase (R2 = 0.37, p = 0.005). While these data provide a valuable dataset for the modelling of radiobiological responses, the differences in the predictive power of residual DSBs between CRISPR-modified and other subgroups suggest that genetic alterations in other pathways, such as proliferation and metabolism, may have a greater impact on cellular radiation response. These pathways are often neglected in response modelling and should be considered in the future. Full article
(This article belongs to the Special Issue Radiation Damage in Biomolecules and Cells 3.0)
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15 pages, 3412 KiB  
Article
A Mission to Mars: Prediction of GCR Doses and Comparison with Astronaut Dose Limits
by Ricardo L. Ramos, Mario P. Carante, Alfredo Ferrari, Paola Sala, Valerio Vercesi and Francesca Ballarini
Int. J. Mol. Sci. 2023, 24(3), 2328; https://doi.org/10.3390/ijms24032328 - 24 Jan 2023
Cited by 4 | Viewed by 1811
Abstract
Long-term human space missions such as a future journey to Mars could be characterized by several hazards, among which radiation is one the highest-priority problems for astronaut health. In this work, exploiting a pre-existing interface between the BIANCA biophysical model and the FLUKA [...] Read more.
Long-term human space missions such as a future journey to Mars could be characterized by several hazards, among which radiation is one the highest-priority problems for astronaut health. In this work, exploiting a pre-existing interface between the BIANCA biophysical model and the FLUKA Monte Carlo transport code, a study was performed to calculate astronaut absorbed doses and equivalent doses following GCR exposure under different shielding conditions. More specifically, the interface with BIANCA allowed us to calculate both the RBE for cell survival, which is related to non-cancer effects, and that for chromosome aberrations, related to the induction of stochastic effects, including cancer. The results were then compared with cancer and non-cancer astronaut dose limits. Concerning the stochastic effects, the equivalent doses calculated by multiplying the absorbed dose by the RBE for chromosome aberrations (“high-dose method”) were similar to those calculated using the Q-values recommended by ICRP. For a 650-day mission at solar minimum (representative of a possible Mars mission scenario), the obtained values are always lower than the career limit recommended by ICRP (1 Sv), but higher than the limit of 600 mSv recently adopted by NASA. The comparison with the JAXA limits is more complex, since they are age and sex dependent. Concerning the deterministic limits, even for a 650-day mission at solar minimum, the values obtained by multiplying the absorbed dose by the RBE for cell survival are largely below the limits established by the various space agencies. Following this work, BIANCA, interfaced with an MC transport code such as FLUKA, can now predict RBE values for cell death and chromosome aberrations following GCR exposure. More generally, both at solar minimum and at solar maximum, shielding of 10 g/cm2 Al seems to be a better choice than 20 g/cm2 for astronaut protection against GCR. Full article
(This article belongs to the Special Issue Radiation Damage in Biomolecules and Cells 3.0)
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17 pages, 774 KiB  
Article
Track Structure-Based Simulations on DNA Damage Induced by Diverse Isotopes
by Pavel Kundrát, Werner Friedland and Giorgio Baiocco
Int. J. Mol. Sci. 2022, 23(22), 13693; https://doi.org/10.3390/ijms232213693 - 08 Nov 2022
Cited by 1 | Viewed by 1347
Abstract
Diverse isotopes such as 2H, 3He, 10Be, 11C and 14C occur in nuclear reactions in ion beam radiotherapy, in cosmic ray shielding, or are intentionally accelerated in dating techniques. However, only a few studies have specifically addressed the [...] Read more.
Diverse isotopes such as 2H, 3He, 10Be, 11C and 14C occur in nuclear reactions in ion beam radiotherapy, in cosmic ray shielding, or are intentionally accelerated in dating techniques. However, only a few studies have specifically addressed the biological effects of diverse isotopes and were limited to energies of several MeV/u. A database of simulations with the PARTRAC biophysical tool is presented for H, He, Li, Be, B and C isotopes at energies from 0.5 GeV/u down to stopping. The doses deposited to a cell nucleus and also the yields per unit dose of single- and double-strand breaks and their clusters induced in cellular DNA are predicted to vary among diverse isotopes of the same element at energies < 1 MeV/u, especially for isotopes of H and He. The results may affect the risk estimates for astronauts in deep space missions or the models of biological effectiveness of ion beams and indicate that radiation protection in 14C or 10Be dating techniques may be based on knowledge gathered with 12C or 9Be. Full article
(This article belongs to the Special Issue Radiation Damage in Biomolecules and Cells 3.0)
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Review

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20 pages, 1265 KiB  
Review
A Cross-Talk about Radioresistance in Lung Cancer—How to Improve Radiosensitivity According to Chinese Medicine and Medicaments That Commonly Occur in Pharmacies
by Paulina Nowak, Iwona Bil-Lula and Mariola Śliwińska-Mossoń
Int. J. Mol. Sci. 2023, 24(13), 11206; https://doi.org/10.3390/ijms241311206 - 07 Jul 2023
Cited by 2 | Viewed by 1633
Abstract
Lung cancer is one of the most common cancers in the population and is characterized by non-specific symptoms that delay the diagnosis and reduce the effectiveness of oncological treatment. Due to the difficult placement of the tumor, one of the main methods of [...] Read more.
Lung cancer is one of the most common cancers in the population and is characterized by non-specific symptoms that delay the diagnosis and reduce the effectiveness of oncological treatment. Due to the difficult placement of the tumor, one of the main methods of lung cancer treatment is radiotherapy, which damages the DNA of cancer cells, inducing their apoptosis. However, resistance to ionizing radiation may develop during radiotherapy cycles, leading to an increase in the number of DNA points of control that protect cells from apoptosis. Cancer stem cells are essential for radioresistance, and due to their ability to undergo epithelial–mesenchymal transition, they modify the phenotype, bypassing the genotoxic effect of radiotherapy. It is therefore necessary to search for new methods that could improve the cytotoxic effect of cells through new mechanisms of action. Chinese medicine, with several thousand years of tradition, offers a wide range of possibilities in the search for compounds that could be used in conventional medicine. This review introduces the potential candidates that may present a radiosensitizing effect on lung cancer cells, breaking their radioresistance. Additionally, it includes candidates taken from conventional medicine—drugs commonly available in pharmacies, which may also be significant candidates. Full article
(This article belongs to the Special Issue Radiation Damage in Biomolecules and Cells 3.0)
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