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The Emerging Role of Molecular Radiation Sciences in Biomedical Applications
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The Emerging Role of Molecular Radiation Sciences in Biomedical Applications

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Physical Chemistry and Chemical Physics".

Deadline for manuscript submissions: closed (1 July 2023) | Viewed by 12012

Special Issue Editors

Dr. Dimitris Emfietzoglou

E-Mail Website
Guest Editor
Medical Physics Laboratory, Department of Medicine, University of Ioannina, 45110 Ioannina, Greece
Interests: Monte Carlo radiation transport; microdosimetry; track-structure; radiation physics, medical physics
Special Issues, Collections and Topics in MDPI journals
Dr. Weibo Li

E-Mail Website
Guest Editor
Institute of Radiation Medicine, Helmholtz Munich - German Research Center for Environmental Health (GmbH), Ingolstädter Landstraße 1, 85764 Neuherberg, Germany
Interests: pharmacokinetic modelling; radiation dosimetry in medicine, Monte Carlo simulation; radiopharmaceutical therapy; radiobiological modelling

Special Issue Information

Dear Colleagues, 

The current practice of radiotherapy (both external and internal) and radiation protection relies on radiation absorbed dose calculations (and/or measurements) averaged over macroscopic (mm- to cm-size) target and non-target volumes, which are subsequently combined with empirical dose–response models to predict radiation effects at the tissue, organ, and whole-body level. This is several orders of magnitude higher than the molecular scale that dictates radiobiological effects at the cellular and DNA levels that are the precursors of the toxic (deterministic) and carcinogenic (stochastic) effects following exposure to ionizing radiation. Molecular radiation science provides the scientific framework for developing mechanistically motivated radiation bioeffect models that may supplement (or even replace) empirical models in non-conventional exposure scenarios where epidemiological (or other empirical) data are limited. Furthermore, molecular radiation science offers the potential of predicting cellular radiation effects a priori, by following the complete chain from the physical interactions to the chemical reactions and biological damage. The physical basis of molecular radiation science goes well beyond absorbed dose, aiming to capture the stochastic nature of energy deposition at the microscopic scale and the role of different energy absorption mechanisms, ultimately leading to the concept of the radiation track-structure. The latter is better suited to deal with the highly non-uniform distributions of energy deposition and chemical species which is encountered in irradiated microscopic target volumes at short time scales. This is the case, for example, in radionuclide therapy and hadron therapy, or in the ultra-high dose-rates of FLASH radiotherapy. Furthermore, the knowledge of radiation track structures and induced radiobiological effects at the molecular scale will be integrated to the science of radiation risk assessment. The present Special Issue is envisioned to motivate further advancements in all aspects of molecular radiation sciences (which includes radiation physics, chemistry, and biology) to fill the aforementioned knowledge gap.

Dr. Dimitris Emfietzoglou
Dr. Weibo Li
Guest Editors

Manuscript Submission Information

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Keywords

  • radiation interactions
  • radiation track-structure
  • radiation chemistry
  • Monte Carlo simulations
  • nanodosimetry
  • microdosimetry
  • DNA radiobiology
  • biophysical modeling
  • modeling radiotherapy outcome
  • molecular radiotherapy
  • radiopharmaceutical therapy
  • FLASH radiobiology
  • quality factor
  • radiation risk

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Published Papers (5 papers)

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Research

14 pages, 3606 KiB  
Article
An Analytical Method for Quantifying the Yields of DNA Double-Strand Breaks Coupled with Strand Breaks by γ-H2AX Focus Formation Assay Based on Track-Structure Simulation
by Yoshie Yachi, Yusuke Matsuya, Yuji Yoshii, Hisanori Fukunaga, Hiroyuki Date and Takeshi Kai
Int. J. Mol. Sci. 2023, 24(2), 1386; https://doi.org/10.3390/ijms24021386 - 10 Jan 2023
Cited by 5 | Viewed by 1901
Abstract
Complex DNA double-strand break (DSB), which is defined as a DSB coupled with additional strand breaks within 10 bp in this study, induced after ionizing radiation or X-rays, is recognized as fatal damage which can induce cell death with a certain probability. In [...] Read more.
Complex DNA double-strand break (DSB), which is defined as a DSB coupled with additional strand breaks within 10 bp in this study, induced after ionizing radiation or X-rays, is recognized as fatal damage which can induce cell death with a certain probability. In general, a DSB site inside the nucleus of live cells can be experimentally detected using the γ-H2AX focus formation assay. DSB complexity is believed to be detected by analyzing the focus size using such an assay. However, the relationship between focus size and DSB complexity remains uncertain. In this study, using Monte Carlo (MC) track-structure simulation codes, i.e., an in-house WLTrack code and a Particle and Heavy Ion Transport code System (PHITS), we developed an analytical method for qualifying the DSB complexity induced by photon irradiation from the microscopic image of γ-H2AX foci. First, assuming that events (i.e., ionization and excitation) potentially induce DNA strand breaks, we scored the number of events in a water cube (5.03 × 5.03 × 5.03 nm3) along electron tracks. Second, we obtained the relationship between the number of events and the foci size experimentally measured by the γ-H2AX focus formation assay. Third, using this relationship, we evaluated the degree of DSB complexity induced after photon irradiation for various X-ray spectra using the foci size, and the experimental DSB complexity was compared to the results estimated by the well-verified DNA damage estimation model in the PHITS code. The number of events in a water cube was found to be proportional to foci size, suggesting that the number of events intrinsically related to DSB complexity at the DNA scale. The developed method was applicable to focus data measured for various X-ray spectral situations (i.e., diagnostic kV X-rays and therapeutic MV X-rays). This method would contribute to a precise understanding of the early biological impacts of photon irradiation by means of the γ-H2AX focus formation assay. Full article
(This article belongs to the Special Issue The Emerging Role of Molecular Radiation Sciences in Biomedical Applications)
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17 pages, 4233 KiB  
Article
Modeling of DNA Damage Repair and Cell Response in Relation to p53 System Exposed to Ionizing Radiation
by Ankang Hu, Wanyi Zhou, Zhen Wu, Hui Zhang, Junli Li and Rui Qiu
Int. J. Mol. Sci. 2022, 23(19), 11323; https://doi.org/10.3390/ijms231911323 - 26 Sep 2022
Cited by 6 | Viewed by 2241
Abstract
Repair of DNA damage induced by ionizing radiation plays an important role in the cell response to ionizing radiation. Radiation-induced DNA damage also activates the p53 system, which determines the fate of cells. The kinetics of repair, which is affected by the cell [...] Read more.
Repair of DNA damage induced by ionizing radiation plays an important role in the cell response to ionizing radiation. Radiation-induced DNA damage also activates the p53 system, which determines the fate of cells. The kinetics of repair, which is affected by the cell itself and the complexity of DNA damage, influences the cell response and fate via affecting the p53 system. To mechanistically study the influences of the cell response to different LET radiations, we introduce a new repair module and a p53 system model with NASIC, a Monte Carlo track structure code. The factors determining the kinetics of the double-strand break (DSB) repair are modeled, including the chromosome environment and complexity of DSB. The kinetics of DSB repair is modeled considering the resection-dependent and resection-independent compartments. The p53 system is modeled by simulating the interactions among genes and proteins. With this model, the cell responses to low- and high-LET irradiation are simulated, respectively. It is found that the kinetics of DSB repair greatly affects the cell fate and later biological effects. A large number of DSBs and a slow repair process lead to severe biological consequences. High-LET radiation induces more complex DSBs, which can be repaired by slow processes, subsequently resulting in a longer cycle arrest and, furthermore, apoptosis and more secreting of TGFβ. The Monte Carlo track structure simulation with a more realistic repair module and the p53 system model developed in this study can expand the functions of the NASIC code in simulating mechanical radiobiological effects. Full article
(This article belongs to the Special Issue The Emerging Role of Molecular Radiation Sciences in Biomedical Applications)
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12 pages, 1967 KiB  
Article
Evaluating the Suitability of 3D Bioprinted Samples for Experimental Radiotherapy: A Pilot Study
by Munir A. Al-Zeer, Franziska Prehn, Stefan Fiedler, Ulrich Lienert, Michael Krisch, Johanna Berg, Jens Kurreck, Guido Hildebrandt and Elisabeth Schültke
Int. J. Mol. Sci. 2022, 23(17), 9951; https://doi.org/10.3390/ijms23179951 - 1 Sep 2022
Cited by 7 | Viewed by 2241
Abstract
Radiotherapy is an important component in the treatment of lung cancer, one of the most common cancers worldwide, frequently resulting in death within only a few years of diagnosis. In order to evaluate new therapeutic approaches and compare their efficiency with regard to [...] Read more.
Radiotherapy is an important component in the treatment of lung cancer, one of the most common cancers worldwide, frequently resulting in death within only a few years of diagnosis. In order to evaluate new therapeutic approaches and compare their efficiency with regard to tumour control at a pre-clinical stage, it is important to develop standardized samples which can serve as inter-institutional outcome controls, independent of differences in local technical parameters or specific techniques. Recent developments in 3D bioprinting techniques could provide a sophisticated solution to this challenge. We have conducted a pilot project to evaluate the suitability of standardized samples generated from 3D printed human lung cancer cells in radiotherapy studies. The samples were irradiated at high dose rates using both broad beam and microbeam techniques. We found the 3D printed constructs to be sufficiently mechanically stable for use in microbeam studies with peak doses up to 400 Gy to test for cytotoxicity, DNA damage, and cancer cell death in vitro. The results of this study show how 3D structures generated from human lung cancer cells in an additive printing process can be used to study the effects of radiotherapy in a standardized manner. Full article
(This article belongs to the Special Issue The Emerging Role of Molecular Radiation Sciences in Biomedical Applications)
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28 pages, 10725 KiB  
Article
Geometrical Properties of the Nucleus and Chromosome Intermingling Are Possible Major Parameters of Chromosome Aberration Formation
by Floriane Poignant, Ianik Plante, Zarana S. Patel, Janice L. Huff and Tony C. Slaba
Int. J. Mol. Sci. 2022, 23(15), 8638; https://doi.org/10.3390/ijms23158638 - 3 Aug 2022
Cited by 7 | Viewed by 2179
Abstract
Ionizing radiation causes chromosome aberrations, which are possible biomarkers to assess space radiation cancer risks. Using the Monte Carlo codes Relativistic Ion Tracks (RITRACKS) and Radiation-Induced Tracks, Chromosome Aberrations, Repair and Damage (RITCARD), we investigated how geometrical properties of the cell nucleus, irradiated [...] Read more.
Ionizing radiation causes chromosome aberrations, which are possible biomarkers to assess space radiation cancer risks. Using the Monte Carlo codes Relativistic Ion Tracks (RITRACKS) and Radiation-Induced Tracks, Chromosome Aberrations, Repair and Damage (RITCARD), we investigated how geometrical properties of the cell nucleus, irradiated with ion beams of linear energy transfer (LET) ranging from 0.22 keV/μm to 195 keV/μm, influence the yield of simple and complex exchanges. We focused on the effect of (1) nuclear volume by considering spherical nuclei of varying radii; (2) nuclear shape by considering ellipsoidal nuclei of varying thicknesses; (3) beam orientation; and (4) chromosome intermingling by constraining or not constraining chromosomes in non-overlapping domains. In general, small nuclear volumes yield a higher number of complex exchanges, as compared to larger nuclear volumes, and a higher number of simple exchanges for LET < 40 keV/μm. Nuclear flattening reduces complex exchanges for high-LET beams when irradiated along the flattened axis. The beam orientation also affects yields for ellipsoidal nuclei. Reducing chromosome intermingling decreases both simple and complex exchanges. Our results suggest that the beam orientation, the geometry of the cell nucleus, and the organization of the chromosomes within are important parameters for the formation of aberrations that must be considered to model and translate in vitro results to in vivo risks. Full article
(This article belongs to the Special Issue The Emerging Role of Molecular Radiation Sciences in Biomedical Applications)
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39 pages, 1860 KiB  
Article
Energy Deposition around Swift Carbon-Ion Tracks in Liquid Water
by Pablo de Vera, Simone Taioli, Paolo E. Trevisanutto, Maurizio Dapor, Isabel Abril, Stefano Simonucci and Rafael Garcia-Molina
Int. J. Mol. Sci. 2022, 23(11), 6121; https://doi.org/10.3390/ijms23116121 - 30 May 2022
Cited by 8 | Viewed by 2553
Abstract
Energetic carbon ions are promising projectiles used for cancer radiotherapy. A thorough knowledge of how the energy of these ions is deposited in biological media (mainly composed of liquid water) is required. This can be attained by means of detailed computer simulations, both [...] Read more.
Energetic carbon ions are promising projectiles used for cancer radiotherapy. A thorough knowledge of how the energy of these ions is deposited in biological media (mainly composed of liquid water) is required. This can be attained by means of detailed computer simulations, both macroscopically (relevant for appropriately delivering the dose) and at the nanoscale (important for determining the inflicted radiobiological damage). The energy lost per unit path length (i.e., the so-called stopping power) of carbon ions is here theoretically calculated within the dielectric formalism from the excitation spectrum of liquid water obtained from two complementary approaches (one relying on an optical-data model and the other exclusively on ab initio calculations). In addition, the energy carried at the nanometre scale by the generated secondary electrons around the ion’s path is simulated by means of a detailed Monte Carlo code. For this purpose, we use the ion and electron cross sections calculated by means of state-of-the art approaches suited to take into account the condensed-phase nature of the liquid water target. As a result of these simulations, the radial dose around the ion’s path is obtained, as well as the distributions of clustered events in nanometric volumes similar to the dimensions of DNA convolutions, contributing to the biological damage for carbon ions in a wide energy range, covering from the plateau to the maximum of the Bragg peak. Full article
(This article belongs to the Special Issue The Emerging Role of Molecular Radiation Sciences in Biomedical Applications)
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