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Keywords = low-LET radiation

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14 pages, 965 KB  
Article
A Procedure for Fast Circuit Cross Section Estimation
by Clayton R. Farias, Tiago R. Balen and Paulo F. Butzen
Chips 2026, 5(1), 2; https://doi.org/10.3390/chips5010002 - 13 Jan 2026
Viewed by 103
Abstract
Semiconductor technologies are susceptible to radiation effects. The particle incidence in susceptible areas of an integrated circuit (IC) can generate physical interactions capable of producing errors. This paper predicts the IC cross sections for Single Event Effects. The cross section is a metric [...] Read more.
Semiconductor technologies are susceptible to radiation effects. The particle incidence in susceptible areas of an integrated circuit (IC) can generate physical interactions capable of producing errors. This paper predicts the IC cross sections for Single Event Effects. The cross section is a metric that provides an IC’s susceptibility to radiation. It deals with particle source interaction and physical design volumes. This work evaluates the IC cross section, exploring the physical design characteristics of susceptible regions in logic gates. It explores particles with low LET, identifying the charge collection areas. Also, the heavy ions are used to evaluate the critical cross section range. Distinct benchmark circuits were simulated to characterize sensitivity trends. The influence of circuit input conditions along with cells’ susceptibility reveals significant findings. The results indicate a difference up to ten times between low- and high-energy particles. Consequently, predicting the IC cross section at an early stage of the design flow is essential, especially for electronics devices used in radiation environments. Full article
(This article belongs to the Special Issue New Research in Microelectronics and Electronics)
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14 pages, 1247 KB  
Article
Evidence for Quasi-High-LET Biological Effects in Clinical Proton Beams That Suppress c-NHEJ and Enhance HR and Alt-EJ
by Emil Mladenov, Mina Pressler, Veronika Mladenova, Aashish Soni, Fanghua Li, Feline Heinzelmann, Johannes Niklas Esser, Razan Hessenow, Eleni Gkika, Verena Jendrossek, Beate Timmermann, Martin Stuschke and George Iliakis
Cells 2026, 15(1), 86; https://doi.org/10.3390/cells15010086 - 4 Jan 2026
Viewed by 336
Abstract
Protons are conventionally regarded as a low-linear energy transfer (low-LET) radiation modality with a relative biological effectiveness (RBE) of 1.1, suggesting direct mechanistic similarity to X-rays in the underpinning biological effects. However, exposure to spread-out Bragg peak (SOBP) protons reveals instructive deviations from [...] Read more.
Protons are conventionally regarded as a low-linear energy transfer (low-LET) radiation modality with a relative biological effectiveness (RBE) of 1.1, suggesting direct mechanistic similarity to X-rays in the underpinning biological effects. However, exposure to spread-out Bragg peak (SOBP) protons reveals instructive deviations from this assumption. Indeed, proton beams have a maximum LET of ~5 keV/µm but display reduced reliance on classical non-homologous end joining (c-NHEJ) as well as an increased dependence on homologous recombination (HR) and alternative end joining (alt-EJ). These features are well described in cells exposed to high-LET radiation and typically manifest between 100 and 150 keV/µm. We hypothesized that this apparent discrepancy reflects biological consequences of proton-beam properties that remain uncharacterized. In the present study, we outline exploratory experiments aiming at uncovering such mechanisms. We begin by investigating for both entrance and SOBP protons the dose-dependent engagement of HR we recently showed for X-rays. Consistent with our previous findings with X-rays, HR engagement after exposure to both types of proton beams declined with dose, from ~80% at 0.2 Gy to less than 20% at higher doses. RAD51/γH2AX foci ratios, reflecting HR engagement, were modestly higher following proton irradiation, in line with increased HR utilization. G2-checkpoint activation, previously linked to HR, was also stronger after exposure to protons, as was DNA end resection. Moreover, the formation of structural chromosomal abnormalities (SCAs) was higher for SOBP than entrance protons and X-rays. Collectively, our results suggest quasi-high-LET characteristics for proton beams and raise the question as to the physical proton properties that underpin them. We discuss that the commonly employed definition of LET may be insufficient for this purpose. Full article
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19 pages, 754 KB  
Review
Novel Physical and Biological Applications of Carbon Ion Radiotherapy
by Danushka Seneviratne, Prapannajeet Biswal and Sunil Krishnan
Cancers 2026, 18(1), 113; https://doi.org/10.3390/cancers18010113 - 30 Dec 2025
Viewed by 444
Abstract
Carbon ion radiation therapy (CIRT) is a high-LET radiotherapy, which distinguishes itself from traditional low-LET radiation, such as photons and protons, through its unique physical aspects, biological attributes, and the dramatically increased damage it causes within cellular DNA. Given its distinctive characteristics, it [...] Read more.
Carbon ion radiation therapy (CIRT) is a high-LET radiotherapy, which distinguishes itself from traditional low-LET radiation, such as photons and protons, through its unique physical aspects, biological attributes, and the dramatically increased damage it causes within cellular DNA. Given its distinctive characteristics, it is expected to improve the therapeutic ratio of radiation treatments and enhance treatment outcomes in traditionally radiation-resistant tumor histologies. Despite these unique properties, much remains to be understood regarding the clinical use of CIRT before its full potential can be realized. In this review, we summarize the distinct advantages of CIRT with regard to its physical and biological qualities and discuss the possibilities for novel applications of this technology through the exploitation of its immunomodulatory potential, abscopal impacts, and its ability to generate direct, oxygen-independent radiation damage within treated tumors. Full article
(This article belongs to the Section Methods and Technologies Development)
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17 pages, 1223 KB  
Article
Molecular Hydrogen as an Antioxidant and Radioprotector: Mechanistic Insights from Monte Carlo Radiation-Chemical Simulations
by Sumaiya Akhter Ria, Jintana Meesungnoen and Jean-Paul Jay-Gerin
Antioxidants 2025, 14(9), 1054; https://doi.org/10.3390/antiox14091054 - 27 Aug 2025
Viewed by 1972
Abstract
(1) Background: Water, comprising about 70–80% of cellular mass, is the most abundant constituent of living cells. Upon exposure to ionizing radiation, water undergoes radiolysis, generating a variety of reactive species, including free radicals and molecular products. Among these, hydroxyl radicals ( [...] Read more.
(1) Background: Water, comprising about 70–80% of cellular mass, is the most abundant constituent of living cells. Upon exposure to ionizing radiation, water undergoes radiolysis, generating a variety of reactive species, including free radicals and molecular products. Among these, hydroxyl radicals (OH) are particularly damaging due to their very high reactivity and their capacity to induce oxidative injury to vital biomolecules such as DNA, membrane lipids, and proteins. From a radiation-chemical perspective, this study investigates the selective scavenging ability of molecular hydrogen (H2) toward OH radicals, with the aim of evaluating its potential as an antioxidant and radioprotective agent; (2) Methods: We employed our Monte Carlo track chemistry simulation code, IONLYS-IRT, to model the time-dependent yields of ROS in a neutral, aerated aqueous environment. The simulations included varying concentrations of dissolved H2 and, for comparison, cystamine—a well-known sulfur-containing radioprotector and antioxidant. Irradiation was simulated using 300 MeV protons, chosen to mimic the radiolytic effects of low linear energy transfer (LET) radiation, such as that of 60Co γ-rays or fast (>1 MeV) electrons; (3) Results: Our simulations quantitatively demonstrated that H2 selectively scavenges OH radicals. Nevertheless, its scavenging efficiency was consistently lower than that of cystamine, which produced a faster and more pronounced suppression of OH due to its higher reactivity and superior radical-quenching capacity; (4) Conclusions: Molecular hydrogen offers several unique advantages, including low toxicity, high diffusivity, selective scavenging of OH radicals, and well-documented anti-inflammatory effects. Although it is less potent than cystamine in terms of radical-scavenging efficiency, its excellent safety profile and biological compatibility position H2 as a promising radioprotector and antioxidant for therapeutic applications targeting radiation-induced oxidative stress and inflammation. Full article
(This article belongs to the Section ROS, RNS and RSS)
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8 pages, 543 KB  
Communication
Assessment of Tumor Relative Biological Effectiveness in Low-LET Proton Irradiation
by Ying-Chun Lin, Jiamin Mo and Yuan-Hao Lee
Biomedicines 2025, 13(8), 1823; https://doi.org/10.3390/biomedicines13081823 - 25 Jul 2025
Viewed by 812
Abstract
Background/Objectives: Within the range of spread-out Bragg peak (SOBP), LET (linear energy transfer) gradually increases from proton beam entrance point toward the beam exit direction. While it is expected that the change in LET would lead to correspondent change in RBE (relative [...] Read more.
Background/Objectives: Within the range of spread-out Bragg peak (SOBP), LET (linear energy transfer) gradually increases from proton beam entrance point toward the beam exit direction. While it is expected that the change in LET would lead to correspondent change in RBE (relative biological effectiveness) on many human cell lines, the incomplete cell killing due to low LET can result in tumor recurrence. Hence, this study aimed to assess the RBE on different cancer cell lines along low-LET proton SOBP. Methods: The clonogenicity of A549 and Panc-1 cells after irradiation was evaluated for investigating cell radiosensitivity in response to different types of radiation. The isoeffect doses of 6-MV photon and low-LET proton beams that resulted in equivalent cell surviving fractions at proton dose of 2 or 4 Gy were compared. Results: Ratios of α/β of A549 and Panc-1 cells from photon irradiation are 51.69 and −0.7747, respectively; RBE (2 Gy proton SOBP) on A549 and Panc-1 cells are 0.7403 ± 0.3324 and 1.0986 ± 0.3984, respectively. In addition, the change in RBE with proton LET was in a cell-specific and dose-dependent manner (LET-RBE linear correlations: A549 cells [r = 0.4673, p = 0.2430] vs. Panc-1 cells at 4 Gy [r = 0.7085, p = 0.0492]; Panc-1 cells at 2 Gy [r = −0.4123, p = 0.3100] vs. 4 Gy [r = 0.7085, p = 0.0492]). Conclusions: Compared with A549 cells, Panc-1 cells present greater resistance to low-LET proton beams. In addition, currently employed generic RBE value at 1.1 for proton therapy neglected the variation in cell-/tumor-specific radiobiological responses toward different dose levels of proton beams. Full article
(This article belongs to the Special Issue New Insights in Radiotherapy: Bridging Radiobiology and Oncology)
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15 pages, 2646 KB  
Article
Radiation Quality-Dependent Progressive Increase in Oxidative DNA Damage and Intestinal Tumorigenesis in Apc1638N/+ Mice
by Kamendra Kumar, Santosh Kumar, Jerry Angdisen, Kamal Datta, Albert J. Fornace and Shubhankar Suman
Curr. Oncol. 2025, 32(7), 382; https://doi.org/10.3390/curroncol32070382 - 1 Jul 2025
Cited by 4 | Viewed by 1421
Abstract
Exposure to high-linear energy transfer (LET) heavy ions, such as 28Si, poses a significant cancer risk for astronauts. While previous studies have linked high-LET radiation exposure to persistent oxidative stress and dysregulated stress responses in intestinal crypt cells with an increased risk [...] Read more.
Exposure to high-linear energy transfer (LET) heavy ions, such as 28Si, poses a significant cancer risk for astronauts. While previous studies have linked high-LET radiation exposure to persistent oxidative stress and dysregulated stress responses in intestinal crypt cells with an increased risk of tumorigenesis, the relationship between IR-induced oxidative DNA damage and intestinal cancer risk remains incompletely understood. Here, we investigated the time-dependent effects of 28Si-ion radiation on intestinal tumorigenesis and oxidative DNA damage in Apc1638N/+ mice, a model for human intestinal cancer predisposition. Male Apc1638N/+ mice were exposed to 10 cGy of either γ-rays (low-LET) or 28Si-ions (high-LET), and intestinal tumor burden was assessed at 60 and 150 days post-irradiation. While both radiation groups showed modest, non-significant tumor increases at 60 days, 28Si-irradiated mice exhibited an approximately 2.5-fold increase in tumor incidence by 150 days, with a higher incidence of invasive carcinomas compared to γ and sham groups. Serum 8-OxodG levels, a marker of systemic oxidative stress, were significantly elevated in the 28Si-ion group, correlating with increased intestinal 8-OxodG staining. Additionally, assessment of the proliferation marker Cyclin D1 and metaplasia marker Guanylyl Cyclase C (GUCY2C) also revealed significant crypt cell hyperproliferation accompanied by increased metaplasia in 28Si-exposed mouse intestines. Positive correlations between serum 8-OxodG and tumor-associated endpoints provide compelling evidence that exposure to 28Si-ions induces progressive intestinal tumorigenesis through sustained oxidative DNA damage, crypt cell hyperproliferation, and metaplastic transformation. This study provides evidence in support of the radiation quality-dependent progressive increase in systemic and intestinal levels of 8-OxodG during intestinal carcinogenesis. Moreover, the progressive increase in oxidative DNA damage and simultaneous increase in oncogenic events after 28Si exposure also suggest that non-targeted effects might be a significant player in space radiation-induced intestinal cancer development. The correlation between serum 8-OxodG and oncogenic endpoints supports its potential utility as a predictive biomarker of high-LET IR-induced intestinal carcinogenesis, with implications for astronaut health risk monitoring during long-duration space missions. Full article
(This article belongs to the Section Gastrointestinal Oncology)
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14 pages, 1097 KB  
Article
Modeling the Impact of Viscosity on Fricke Gel Dosimeter Radiolysis: A Radiation Chemical Simulation Approach
by Sumaiya Akhter Ria, Jintana Meesungnoen and Jean-Paul Jay-Gerin
Gels 2025, 11(7), 489; https://doi.org/10.3390/gels11070489 - 24 Jun 2025
Cited by 1 | Viewed by 1151
Abstract
The Fricke gel dosimeter, a hydrogel-based chemical dosimeter containing dissolved ferrous sulfate, measures 3D radiation dose distributions by oxidizing Fe2+ to Fe3+ upon irradiation. This study investigates the variation in Fricke yield, G(Fe3+), from a radiation–chemical perspective in [...] Read more.
The Fricke gel dosimeter, a hydrogel-based chemical dosimeter containing dissolved ferrous sulfate, measures 3D radiation dose distributions by oxidizing Fe2+ to Fe3+ upon irradiation. This study investigates the variation in Fricke yield, G(Fe3+), from a radiation–chemical perspective in both standard and gel-like Fricke systems of varying viscosities, under low- and high-linear energy transfer (LET) conditions. We employed our Monte Carlo track chemistry code IONLYS-IRT, using protons of 300 MeV (LET~0.3 keV/µm) and 1 MeV (LET~25 keV/µm) as radiation sources. To assess the impact of viscosity on G(Fe3+), we systematically varied the diffusion coefficients of all radiolytic species in the Fricke gel, including Fe2+ and Fe3+ ions. Increasing gel viscosity reduces Fe3+ diffusion and stabilizes spatial dose distributions but also lowers G(Fe3+), compromising measurement accuracy and sensitivity—especially under high-LET irradiation. Our results show that an optimal Fricke gel dosimeter must balance these competing factors. Simulations with lower sulfuric acid concentrations (e.g., 0.05 M vs. 0.4 M) further revealed that G(Fe3+) values at ~100 s are nearly identical for both low- and high-LET conditions. This study underscores the utility of Monte Carlo simulations in modeling viscosity effects on Fricke gel radiolysis, guiding dosimeter optimization to maximize sensitivity and accuracy while preserving spatial dose distribution integrity. Full article
(This article belongs to the Special Issue Application of Gel Dosimetry)
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17 pages, 1481 KB  
Article
Radiolysis of Sub- and Supercritical Water Induced by 10B(n,α)7Li Recoil Nuclei at 300–500 °C and 25 MPa
by Md Shakhawat Hossen Bhuiyan, Jintana Meesungnoen and Jean-Paul Jay-Gerin
J. Nucl. Eng. 2025, 6(2), 17; https://doi.org/10.3390/jne6020017 - 9 Jun 2025
Viewed by 1285
Abstract
(1) Background: Generation IV supercritical water-cooled reactors (SCWRs), including small modular reactor (SCW-SMR) variants, are pivotal in nuclear technology. Operating at 300–500 °C and 25 MPa, these reactors require detailed understanding of radiation chemistry and transient species to optimize water chemistry, reduce corrosion, [...] Read more.
(1) Background: Generation IV supercritical water-cooled reactors (SCWRs), including small modular reactor (SCW-SMR) variants, are pivotal in nuclear technology. Operating at 300–500 °C and 25 MPa, these reactors require detailed understanding of radiation chemistry and transient species to optimize water chemistry, reduce corrosion, and enhance safety. Boron, widely used as a neutron absorber, plays a significant role in reactor performance and safety. This study focuses on the yields of radiolytic species in subcritical and supercritical water exposed to 4He and 7Li recoil ions from the 10B(n,α)7Li fission reaction in SCWR/SCW-SMR environments. (2) Methods: We use Monte Carlo track chemistry simulations to calculate yields (G values) of primary radicals (eaq, H, and OH) and molecular species (H2 and H2O2) from water radiolysis by α-particles and Li3⁺ recoils across 1 picosecond to 0.1 millisecond timescales. (3) Results: Simulations show substantially lower radical yields, notably eaq and OH, alongside higher molecular product yields compared to low linear energy transfer (LET) radiation, underscoring the high-LET nature of 10B(n,α)7Li recoil nuclei. Key changes include elevated G(OH) and G(H2), and a decrease in G(H), primarily driven during the homogeneous chemical stage of radiolysis by the reaction H + H2O → OH + H2. This reaction significantly contributes to H2 production, potentially reducing the need for added hydrogen in coolant water to mitigate oxidizing species. In supercritical conditions, low G(H₂O₂) suggests that H2O2 is unlikely to be a major contributor to material oxidation. (4) Conclusions: The 10B(n,α)7Li reaction’s yield estimates could significantly impact coolant chemistry strategies in SCWRs and SCW-SMRs. Understanding radiolytic behavior in these conditions aids in refining reactor models and coolant chemistry to minimize corrosion and radiolytic damage. Future experiments are needed to validate these predictions. Full article
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22 pages, 8420 KB  
Article
Relative Biological Effectiveness (RBE) of Monoenergetic Protons: Comparison of Empirical and Biophysical Models
by Dimitris Dalalas, Alexis Papadopoulos, Ioanna Kyriakou, Robert D. Stewart, Pantelis Karaiskos and Dimitris Emfietzoglou
Appl. Sci. 2024, 14(24), 11981; https://doi.org/10.3390/app142411981 - 20 Dec 2024
Viewed by 2108
Abstract
A constant proton relative biological effectiveness (RBE) of 1.1 for tumor control is currently used in proton therapy treatment planning. However, in vitro, in vivo and clinical experiences indicate that proton RBE varies with kinetic energy and, therefore, tissue depth within proton Bragg [...] Read more.
A constant proton relative biological effectiveness (RBE) of 1.1 for tumor control is currently used in proton therapy treatment planning. However, in vitro, in vivo and clinical experiences indicate that proton RBE varies with kinetic energy and, therefore, tissue depth within proton Bragg peaks. A number of published RBE models capture variations in proton RBE with depth. The published models can be sub-divided into empirical (or phenomenological) and biophysical (or mechanistic-inspired) RBE models. Empirical RBE models usually characterize the beam quality through the dose-averaged linear energy transfer (LETD), while most biophysical RBE models relate RBE to the dose-averaged lineal energy (yD). In this work, an analytic microdosimetry model and the Monte Carlo damage simulation code (MCDS) were utilized for the evaluation of the LETD and yD of monoenergetic proton beams in the clinically relevant energy range of 1–250 MeV. The calculated LETD and yD values were then used for the estimation of the RBE for five different cell types at three dose levels (2 Gy, 5 Gy and 7 Gy). Comparisons are made between nine empirical RBE models and two biophysical models, namely, the theory of dual radiation action (TDRA) and the microdosimetric kinetic model (MKM). The results show that, at conventional dose fractions (~2 Gy) and for proton energies which correspond to the proximal and central regions of the spread-out Bragg peak (SOBP), RBE varies from 1.0 to 1.2. At lower proton energies related to the distal SOBP, we find significant deviations from a constant RBE of 1.1, especially for late-responding tissues (low (α/β)R of ~1.5–3.5 Gy) where proton RBE may reach 1.3 to 1.5. For hypofractionated dose fractions (5–7 Gy), deviations from a constant RBE of 1.1 are smaller, but may still be sizeable, yielding RBE values between 1.15 and 1.3. However, large discrepancies among the different models were observed that make the selection of a variable RBE across the SOBP uncertain. Full article
(This article belongs to the Section Applied Physics General)
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15 pages, 4387 KB  
Article
Enhancing Proton Radiosensitivity of Chondrosarcoma Using Nanoparticle-Based Drug Delivery Approaches: A Comparative Study of High- and Low-Energy Protons
by Mihaela Tudor, Roxana Cristina Popescu, Ionela N. Irimescu, Ann Rzyanina, Nicolae Tarba, Anca Dinischiotu, Liviu Craciun, Tiberiu Relu Esanu, Eugeniu Vasile, Andrei Theodor Hotnog, Mihai Radu, Gennady Mytsin, Mona Mihailescu and Diana Iulia Savu
Int. J. Mol. Sci. 2024, 25(21), 11481; https://doi.org/10.3390/ijms252111481 - 25 Oct 2024
Cited by 3 | Viewed by 1650
Abstract
To overcome chondrosarcoma’s (CHS) high chemo- and radioresistance, we used polyethylene glycol-encapsulated iron oxide nanoparticles (IONPs) for the controlled delivery of the chemotherapeutic doxorubicin (IONPDOX) to amplify the cytotoxicity of proton radiation therapy. Human 2D CHS SW1353 cells were treated with [...] Read more.
To overcome chondrosarcoma’s (CHS) high chemo- and radioresistance, we used polyethylene glycol-encapsulated iron oxide nanoparticles (IONPs) for the controlled delivery of the chemotherapeutic doxorubicin (IONPDOX) to amplify the cytotoxicity of proton radiation therapy. Human 2D CHS SW1353 cells were treated with protons (linear energy transfer (LET): 1.6 and 12.6 keV/µm) with and without IONPDOX. Cell survival was assayed using a clonogenic test, and genotoxicity was tested through the formation of micronuclei (MN) and γH2AX foci, respectively. Morphology together with spectral fingerprints of nuclei were measured using enhanced dark-field microscopy (EDFM) assembled with a hyperspectral imaging (HI) module and an axial scanning fluorescence module, as well as scanning electron microscopy (SEM) coupled with energy-dispersive X-Ray spectroscopy (EDX). Cell survival was also determined in 3D SW3153 spheroids following treatment with low-LET protons with/without the IONPDOX compound. IONPDOX increased radiosensitivity following proton irradiation at both LETs in correlation with DNA damage expressed as MN or γH2AX. The IONPDOX–low-LET proton combination caused a more lethal effect compared to IONPDOX–high-LET protons. CHS cell biological alterations were reflected by the modifications in the hyperspectral images and spectral profiles, emphasizing new possible spectroscopic markers of cancer therapy effects. Our findings show that the proposed treatment combination has the potential to improve the management of CHS. Full article
(This article belongs to the Special Issue Implication of Nanoparticles in Cancer Therapy Research, 2nd Edition)
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23 pages, 2031 KB  
Article
Comparative Analysis of Cystamine and Cysteamine as Radioprotectors and Antioxidants: Insights from Monte Carlo Chemical Modeling under High Linear Energy Transfer Radiation and High Dose Rates
by Samafou Penabeï, Jintana Meesungnoen and Jean-Paul Jay-Gerin
Int. J. Mol. Sci. 2024, 25(19), 10490; https://doi.org/10.3390/ijms251910490 - 29 Sep 2024
Cited by 3 | Viewed by 2208
Abstract
This study conducts a comparative analysis of cystamine (RSSR), a disulfide, and cysteamine (RSH), its thiol monomer, to evaluate their efficacy as radioprotectors and antioxidants under high linear energy transfer (LET) and high-dose-rate irradiation conditions. It examines their interactions with reactive primary species [...] Read more.
This study conducts a comparative analysis of cystamine (RSSR), a disulfide, and cysteamine (RSH), its thiol monomer, to evaluate their efficacy as radioprotectors and antioxidants under high linear energy transfer (LET) and high-dose-rate irradiation conditions. It examines their interactions with reactive primary species produced during the radiolysis of the aqueous ferrous sulfate (Fricke) dosimeter, offering insights into the mechanisms of radioprotection and highlighting their potential to enhance the therapeutic index of radiation therapy, particularly in advanced techniques like FLASH radiotherapy. Using Monte Carlo multi-track chemical modeling to simulate the radiolytic oxidation of ferrous to ferric ions in Fricke-cystamine and Fricke-cysteamine solutions, this study assesses the radioprotective and antioxidant properties of these compounds across a variety of irradiation conditions. Concentrations were varied in both aerated (oxygen-rich) and deaerated (hypoxic) environments, simulating conditions akin to healthy tissue and tumors. Both cystamine and cysteamine demonstrate radioprotective and strong antioxidant properties. However, their effectiveness varies significantly depending on the concentration employed, the conditions of irradiation, and whether or not environmental oxygen is present. Specifically, excluding potential in vivo toxicity, cysteamine substantially reduces the adverse effects of ionizing radiation under aerated, low-LET conditions at concentrations above ~1 mM. However, its efficacy is minimal in hypoxic environments, irrespective of the concentration used. Conversely, cystamine consistently offers robust protective effects in both oxygen-rich and oxygen-poor conditions. The distinct protective capacities of cysteamine and cystamine underscore cysteamine’s enhanced potential in radiotherapeutic settings aimed at safeguarding healthy tissues from radiation-induced damage while effectively targeting tumor tissues. This differential effectiveness emphasizes the need for personalized radioprotective strategies, tailored to the specific environmental conditions of the tissue involved. Implementing such approaches is crucial for optimizing therapeutic outcomes and minimizing collateral damage in cancer treatment. Full article
(This article belongs to the Section Physical Chemistry and Chemical Physics)
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11 pages, 454 KB  
Review
FLASH Radiotherapy Versus Conventional Cancer Therapy: Promises, Paradoxes and Problems
by Stephen C. Bondy
Int. J. Transl. Med. 2024, 4(3), 559-569; https://doi.org/10.3390/ijtm4030038 - 11 Sep 2024
Cited by 2 | Viewed by 3727
Abstract
A novel means of applying radiotherapy in cancer treatment is the application of a radiation dose at a very high intensity for a very short time in FLASH radiotherapy (FLASH-RT). This technique involves the exposure of tumors to >40 Gy/s, usually for less [...] Read more.
A novel means of applying radiotherapy in cancer treatment is the application of a radiation dose at a very high intensity for a very short time in FLASH radiotherapy (FLASH-RT). This technique involves the exposure of tumors to >40 Gy/s, usually for less than one second. Studies conducted in cell and preclinical models suggest that FLASH-RT seems less damaging to normal tissues from adverse effects relative to the same overall dose of radiation administered in conventional therapy (CONV-RT), which involves the administration of lower levels of radiation repeated intermittently over a protracted period. In contrast, the susceptibility of tumor tissues to FLASH-RT is not diminished relative to CONV-RT. Within solid tumors, both modes of dispensation of radiation produce an equivalent degree of cell damage. The differential treatment between normal and malignant material has been found in isolated tissues, animal studies and, more recently, in clinical trials. However, the classic radiation concept is that high-energy linear transfer radiation (LET) is more damaging than the equivalent total dose of low LET. Thus, the susceptibility of cells should be greater after short-term exposure to high LET. This article discusses the potential reasons that may account for this discrepancy. While the relative protection given to untransformed tissues by FLASH-RT relative to tumor tissue is a major step forward in radiation therapy for cancer, the processes that lie behind this phenomenon are incompletely understood and are considered here. Full article
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14 pages, 3239 KB  
Article
Radiosensitizing Effect of PARP Inhibition on Chondrosarcoma and Chondrocyte Cells Is Dependent on Radiation LET
by Antoine Gilbert, Mihaela Tudor, Amandine Delaunay, Raphaël Leman, Julien Levilly, Alexandre Atkinson, Laurent Castéra, Anca Dinischiotu, Diana Iulia Savu, Samuel Valable and François Chevalier
Biomolecules 2024, 14(9), 1071; https://doi.org/10.3390/biom14091071 - 27 Aug 2024
Cited by 4 | Viewed by 2130
Abstract
Chondrosarcoma is a rare malignant tumor that forms in bone and cartilage. The primary treatment involves surgical removal of the tumor with a margin of healthy tissue. Especially if complete surgical removal is not possible, radiation therapy and chemotherapy are used in conjunction [...] Read more.
Chondrosarcoma is a rare malignant tumor that forms in bone and cartilage. The primary treatment involves surgical removal of the tumor with a margin of healthy tissue. Especially if complete surgical removal is not possible, radiation therapy and chemotherapy are used in conjunction with surgery, but with a generally low efficiency. Ongoing researches are focused on understanding the genetic and molecular basis of chondrosarcoma following high linear energy transfer (LET) irradiation, which may lead to treatments that are more effective. The goal of this study is to evaluate the differential effects of DNA damage repair inhibitors and high LET irradiation on chondrosarcoma versus chondrocyte cells and the LET-dependency of the effects. Two chondrosarcoma cell lines with different IDH mutation status and one chondrocyte cell line were exposed to low LET (X-ray) and high LET (carbon ion) irradiation in combination with an Olaparib PARP inhibitor. Cell survival and DNA repair mechanisms were investigated. High LET irradiation drastically reduced cell survival, with a biological efficiency three times that of low LET. Olaparib significantly inhibited PARylation in all the tested cells. A significant reduction in cell survival of both chondrosarcoma and chondrocyte cells was observed following the treatment combining Olaparib and X-ray. PARP inhibition induced an increase in PARP-1 expression and a reduced effect on the cell survival of WT IDH chondrosarcoma cells. No radiosensitizing effect was observed in cells exposed to Olaparib paired with high LET irradiation. NHEJ was activated in response to high LET irradiation, neutralizing the PARP inhibition effect in both chondrosarcoma cell lines. When high LET irradiation is not available, PARP inhibition could be used in combination with low LET irradiation, with significant radiosensitizing effects on chondrosarcoma cells. Chondrocytes may be affected by the treatment combination too, showing the need to preserve normal tissues from radiation fields when this kind of treatment is suggested. Full article
(This article belongs to the Special Issue PARPs in Cell Death and PARP Inhibitors in Cancers)
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21 pages, 3012 KB  
Article
Effects of Continuous Prenatal Low Dose Rate Irradiation on Neurobehavior, Hippocampal Cellularity, Messenger RNA and MicroRNA Expression on B6C3F1 Mice
by Feng Ru Tang, Ignacia Braga Tanaka, Hong Wang, Salihah Lau, Satoshi Tanaka, Amanda Tan, Daisaku Takai and Akiko Abe
Cells 2024, 13(17), 1423; https://doi.org/10.3390/cells13171423 - 26 Aug 2024
Cited by 4 | Viewed by 5512
Abstract
Epidemiological, experimental, and ecological data have indicated the controversial effect of in utero chronic low dose rate (<6 mGy/h) with accumulative low (≤100 mGy) or high (>100 mGy) dose radiation exposure. Our main goal of this study was to examine if different low [...] Read more.
Epidemiological, experimental, and ecological data have indicated the controversial effect of in utero chronic low dose rate (<6 mGy/h) with accumulative low (≤100 mGy) or high (>100 mGy) dose radiation exposure. Our main goal of this study was to examine if different low dose rates of chronic pre- and/or post-natal radiation exposure with accumulative high doses could induce hippocampal cellular, mRNA, and miRNA changes leading to neuropsychiatric disorders. The comprehensive mouse phenotypic traits, organ weight, pathological, and blood mRNA and miRNA changes were also studied. Using different approaches including SmithKline, Harwell, Imperial College, Royal Hospital, Phenotype Assessment (SHIRPA), neurobehavioral tests, pathological examination, immunohistochemistry, mRNA and miRNA sequencing, and real-time quantitative polymerase chain reaction (qRT-PCR) validation, we found that in prenatally irradiated (100 mGy/d for 18 days with an accumulative dose of 1.8 Gy) 1-year-old mice, no cellular changes, including immature neurons in the subgranular zone, mature neurons and glial cells in the hilus of the dentate gyrus and development of cognitive impairment, neuropsychiatric disorders, occurred. However, a significant reduction in body weight and mass index (BMI) was indicated by the SHIRPA test. A reduced exploratory behavior was shown by an open field test. Organ weights showed significant reductions in the testes, kidneys, heart, liver and epididymides with no abnormal pathology. mRNA and miRNA sequencing and qRT-PCR validation revealed the upregulation of Rubcnl and Abhd14b, and downregulation of Hspa1b, P4ha1, and Banp genes in both the hippocampus and blood of mice prenatally irradiated with 100 mGy/d. Meanwhile, downregulation of miR-448-3p and miR1298-5p in the hippocampus, miR-320-3p, miR-423-5p, miR-486b-5p, miR-486b-3p, miR-423-3p, miR-652-3p, miR-324-3p, miR-181b-5p, miR-let-7b, and miR-6904-5p in the blood was induced. The target scan revealed that Rubcnl is one of the miR-181b-5p targets in the blood. We, therefore, concluded that prenatal chronic irradiation with a low dose rate of 100 mGy/d and accumulative dose of 1.8 Gy or below might not induce significant adverse health effects on the offspring. Further study of different low dose rate radiation exposures with accumulative high doses may provide threshold doses for authorities or regulators to set new radiation safety guidelines to replace those extrapolated from acute high dose/dose rate irradiation to reduce unnecessary emergency evacuation or spending once a nuclear accident or leakage occurs. Full article
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Article
Fast-Neutron Radiolysis of Sub- and Supercritical Water at 300–600 °C and 25 MPa: A Monte Carlo Track Chemistry Simulation Study
by Md Shakhawat Hossen Bhuiyan, Jintana Meesungnoen, Abida Sultana and Jean-Paul Jay-Gerin
Appl. Sci. 2024, 14(16), 7024; https://doi.org/10.3390/app14167024 - 10 Aug 2024
Cited by 1 | Viewed by 1905
Abstract
(1) Background: Supercritical water-cooled reactors (SCWRs) and their smaller modular variants (SMRs) are part of the ‘Generation IV International Forum’ (GIF) on advanced nuclear energy systems. These reactors operate beyond the critical point of water (tc = 373.95 °C and P [...] Read more.
(1) Background: Supercritical water-cooled reactors (SCWRs) and their smaller modular variants (SMRs) are part of the ‘Generation IV International Forum’ (GIF) on advanced nuclear energy systems. These reactors operate beyond the critical point of water (tc = 373.95 °C and Pc = 22.06 MPa), which introduces specific technical challenges that need to be addressed. The primary concerns involve the effects of intense radiation fields—including fast neutrons, recoil protons/oxygen ions, and γ rays—on the chemistry of the coolant fluid and the integrity of construction materials. (2) Methods: This study employs Monte Carlo simulations of radiation track chemistry to investigate the yields of radiolytic species in SCWRs/SMRs exposed to 2 MeV neutrons. In our calculations, only the contributions from the first three recoil protons with initial energies of 1.264, 0.465, and 0.171 MeV were considered. Our analysis was conducted at both subcritical (300 and 350 °C) and supercritical temperatures (400–600 °C), maintaining a constant pressure of 25 MPa. (3) Results: Our simulations provide insights into the radiolytic formation of chemical species such as eaq, H, H2, OH, and H2O2 from ~1 ps to 1 ms. Compared to data from radiation with low linear energy transfer (LET), the G(eaq) and G(OH) values obtained for fast neutrons show a similar temporal dependence but with smaller amplitude—a result demonstrating the high LET nature of fast neutrons. A notable outcome of our simulations is the marked increase in G(OH) and G(H2), coupled with a corresponding reduction in G(H), observed during the homogeneous chemical stage of radiolysis. This evolution is attributed to the oxidation of water by the H atom according to the reaction H + H2O → OH + H2. This reaction acts as a significant source of H2, potentially reducing the need to add extra hydrogen to the reactor’s coolant water to suppress the net radiolytic production of oxidizing species. Unlike in subcritical water, our simulations also indicate that G(H2O2) remains very low in low-density SCW throughout the interval from ~1 ps to 1 ms, suggesting that H2O2 is less likely to contribute to oxidative stress under these conditions. (4) Conclusions: The results of this study could significantly impact water-chemistry management in the proposed SCWRs and SCW-SMRs, which is crucial for assessing and mitigating the corrosion risks to reactor materials, especially for long-term operation. Full article
(This article belongs to the Section Chemical and Molecular Sciences)
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