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Purpose: Nanoparticles (NPs) as radiosensitizers present a promising strategy for enhancing radiotherapy effectiveness, but their potential is significantly influenced by the properties of their surface coating, which can impact treatment outcomes. Most Monte Carlo studies have focused on metallic NPs without considering the impact of coating layers on radiosensitization. In this study, we aim to assess both the physical and radiobiological effects of nanoparticle coatings in nanoparticle-based radiation therapy. Materials and methods: In this simulation study, we used Geant4 Monte Carlo (MC) toolkit (v10.07.p02) and simulated the bismuth, gold, iridium and gadolinium NPs coated with polyethylene glycol (PEG-400: Density: 1.13 g/cm³, Molar mass: 380–420 g/mol) as radiosensitizer for photon beams of 30, 60 and 100 keV. Secondary electron number and reactive oxygen species enhancement factor were estimated. Also, dose enhancement factor (DEF) was determined in spherical shells with logarithmic scale thickness from the nanoparticle surface to 4 mm. Results: Secondary electron emission was highest at 30 keV for gold, bismuth, and iridium NPs, while gadolinium NPs peaked at 60 keV. Coating reduced electron emissions across all energies, with thicker coatings leading to a more significant decrease. DEF values declined with increasing radial distance from the NP surface and were lower with thicker coatings. For gadolinium NPs, DEF behavior differed due to K-edge energy effects. Reactive species generation varied, showing maximum production at 30 keV for gold, bismuth, and iridium NPs, while gadolinium NPs showed peak activity at 60 keV. PEG coatings enhanced reactive species formation at 100 keV. Conclusion: The findings indicate that the coating layer thickness and material not only influence the emission of secondary particles and DEF but also affect the generation of reactive species from water radiolysis. Specifically, thicker coatings reduce secondary particle emission and DEF, while PEG coatings demonstrate a dual behavior, offering both protective and enhancing effects depending on photon energy. These insights underscore the importance of optimizing NP design and coating in future studies to maximize therapeutic efficacy in nanoparticle-based radiation therapy. [ABSTRACT FROM AUTHOR]

Malignant (high-grade) gliomas are aggressive intrinsic brain tumors that diffusely infiltrate the brain parenchyma. They comprise of World Health Organization (WHO) grade III and IV gliomas. Ionizing radiation or irradiation (IR) is frequently utilized in the treatment of both primary as well as metastatic brain tumors. On the contrary, macrophages (MΦ) are the most copious infiltrating immune cells of all the different cell types colonizing glioma. MΦ at tumor milieu are referred to as tumor-associated macrophages (TAMΦ). In malignant gliomas milieu, TAMΦ are also polarized into two distinct phenotypes such as M1 TAMΦ or M2 TAMΦ, which are capable of inhibiting or promoting tumor growth, respectively. Cranial-IR such as x- and γ-IR are sufficient to induce the migration of peripherally derived MΦ into the brain parenchyma. The IR facilitate a more immunosuppressive milieu via the stimulation of efferocytosis in TAMΦ, and an upsurge of tumor cell engulfment by TAMΦ exhibited detrimental effect of the anti-tumoral immune response in glioma. The MΦ inside the tumor mass are associated with multiple phenomena that include IR resistance and enrichment of the M2 MΦ after IR is able to facilitate glioblastoma multiforme (GBM) recurrence. Reviews on the role of cranial IR-induced peripheral and brain-engrafting macrophages (BeMΦ) in glioma are lacking. Specifically, most studies on peripheral, intrinsic as well as beMΦ on IR focus on WHO grade III and IV. Thus, this review precisely focuses primary on WHO grade III as well as IV gliomas. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Boron neutron capture therapy (BNCT) is a targeted radiotherapy that relies on the 10B (n, α) 7Li reaction, which produces secondary particles with high linear energy transfer (LET), leading to a high relative biological effectiveness (RBE) in tumors. The biological effectiveness of BNCT is influenced by factors such as boron distribution and concentration, necessitating improved methods for assessing its radiobiological effects and clarifying the sensitivity of the differences in different factors to the biological effects.This paper introduces a method to evaluate the biological effects of BNCT using the cellular repair model. This method aims to overcome some of the limitations of current evaluation approaches. The primary goal is to provide guidance for clinical treatments and the development of boron drugs, as well as to investigate the impact of the synergistic effects of mixed radiation fields in BNCT on treatment outcomes.The approach involves three key steps: first, extending the radial energy deposition distribution of BNCT secondary particles using Geant4‐DNA. This allows for the calculation of initial DNA double‐strand breaks (DSBs) distributions for a given absorbed dose. Next, the obtained initial DSB distributions are used for DNA damage repair simulations to generate cell survival curves, then thereby quantifying RBE and compound biological effectiveness (CBE). The study also explores the synergistic effects of the mixed radiation fields in BNCT on assessing biological effects were also explored in depth.The results showed that the RBE of boronophenylalanine (BPA) and sodium borocaptate (BSH) drugs at cell survival fraction 0.01 was 2.50 and 2.15, respectively. The CBE of the boron dose component was 3.60 and 0.73, respectively, and the RBE of the proton component was 3.21, demonstrating that BPA has a significantly higher biological impact than BSH due to superior cellular permeability. The proton dose significance in BNCT treatment is also underscored, necessitating consideration in both experimental and clinical contexts. The study demonstrates that synergistic effects between disparate radiation fields lead to increased misrepairs and enhanced biological impact. Additionally, the biological effect diminishes with rising boron concentration, emphasizing the need to account for intercellular DNA damage heterogeneity.This methodology offers valuable insights for the development of new boron compounds and precise assessment of bio‐weighted doses in clinical settings and can be adapted to other therapeutic modalities. [ABSTRACT FROM AUTHOR]

Simple Summary: Heavy ion radiation, found in outer space and used in some cancer treatments, can damage vital cells in the intestines. Studies using mice show that this type of radiation causes long-lasting stress, accelerated aging, and harmful changes in these cells, which can perturb gut function and increase the risk of developing cancer. Specialized mouse models were employed to monitor how these intestinal stem cells are affected over time after exposure to this radiation. We found that particle radiation caused more stress-induced damage and tumor incidence compared to photon radiation. Intestinal stem cells showed signs of aging and inflammation, which persisted for up to a year. This ongoing stress and damage also disrupt the gut barrier's function and ability to absorb nutrients properly. The findings suggest that astronauts exposed to this radiation during deep space missions might face increased risks of gut dysfunction as well as increased cancer risk. Heavy ion radiation, prevalent in outer space and relevant for radiotherapy, is densely ionizing and poses a risk to intestinal stem cells (ISCs), which are vital for maintaining intestinal homeostasis. Earlier studies have shown that heavy-ion radiation can cause chronic oxidative stress, persistent DNA damage, cellular senescence, and the development of a senescence-associated secretory phenotype (SASP) in mouse intestinal mucosa. However, the specific impact on different cell types, particularly Lgr5+ intestinal stem cells (ISCs), which are crucial for maintaining cellular homeostasis, GI function, and tumor initiation under genomic stress, remains understudied. Using an ISCs-relevant mouse model (Lgr5+ mice) and its GI tumor surrogate (Lgr5+Apc1638N/+ mice), we investigated ISCs-specific molecular alterations after high-LET radiation exposure. Tissue sections were assessed for senescence and SASP signaling at 2, 5 and 12 months post-exposure. Lgr5+ cells exhibited significantly greater oxidative stress following 28Si irradiation compared to γ-ray or controls. Both Lgr5+ cells and Paneth cells showed signs of senescence and developed a senescence-associated secretory phenotype (SASP) after 28Si exposure. Moreover, gene expression of pro-inflammatory and pro-growth SASP factors remained persistently elevated for up to a year post-28Si irradiation. Additionally, p38 MAPK and NF-κB signaling pathways, which are critical for stress responses and inflammation, were also upregulated after 28Si radiation. Transcripts involved in nutrient absorption and barrier function were also altered following irradiation. In Lgr5+Apc1638N/+ mice, tumor incidence was significantly higher in those exposed to 28Si radiation compared to the spontaneous tumorigenesis observed in control mice. Our results indicate that high-LET 28Si exposure induces persistent DNA damage, oxidative stress, senescence, and SASP in Lgr5+ ISCs, potentially predisposing astronauts to altered nutrient absorption, barrier function, and GI carcinogenesis during and after a long-duration outer space mission. [ABSTRACT FROM AUTHOR]

To investigate how absorbed doses to mastication structures in modern radiotherapy (RT) technique for head and neck cancer (HNC) compared with earlier RT techniques and with published trismus tolerance doses. To compare the incidence of radiation-induced trismus by earlier and newer RT techniques. This study investigated two HNC patient cohorts treated with RT in 2007–2012 (three-dimensional conformal radiotherapy [3DCRT] and/or intensity-modulated radiotherapy [IMRT]; n =121 [ Cohort 1 ]) and 2017–2020 (volumetric-modulated arc therapy [VMAT]; n =124 [ Cohort 2 ]). All patients underwent RT without mastication structure–sparing intent, had normal mouth-opening ability before RT, and were prospectively assessed. Trismus was defined as the maximal interincisal opening ≤35 mm at any follow-up (3-, 6-, and 12-months post-RT). The temporomandibular joints (TMJs), masseter, and medial/lateral pterygoid muscles were delineated on the planning CT:s. Mean doses were compared between cohorts, and evaluated with respect to published trismus tolerance doses. P values ≤ 0.05 indicated statistical significance. Within 12 months post RT, 74/121 (61%) of patients in Cohort 1 had experienced trismus compared to 11/124 (9%) in Cohort 2. Averaged mean doses (±S.D.) for the masseter muscles were 35.2±8.3 Gy in Cohort 1 and 20.2±8.7 Gy in Cohort 2 (P <0.001). Corresponding numbers were 19.1±16.2 and 4.3±4.3 Gy for the TMJs, 53.7±10.1 and 40.2±16.8 Gy for the medial pterygoid muscles, and 29.2±18.7 and 9.2±8.4 Gy for the lateral pterygoid muscles (all P <0.001). Masseter muscle doses were below tolerance doses in 23% of patients in Cohort 1 compared with 90% in Cohort 2. The corresponding numbers were 52% and 96% for the TMJs, 8% and 36% for the medial pterygoid muscles and 72% and 100% for the lateral pterygoid muscles. Mastication structure mean doses by more recent RT techniques were generally below proposed tolerance doses, with dose reductions of 10–20 Gy compared with earlier techniques. Modern RT without mastication-structure-sparing intent resulted in below 10% of HNC patients experiencing trismus compared with 60% treated with earlier techniques. • Modern radiotherapy can substantially spare organs-at-risk in head and neck cancer. • Mastication-structure mean radiation doses were reduced by 10–20 Gy. • These dose reductions were accompanied by a trismus reduction from 60% to 10%. [ABSTRACT FROM AUTHOR]

The incident of Chernobyl Nuclear Power Plant (CNPP) explosion has pioneered a plethora of studies unfolding various biological effects of radiation stress on several living systems. Determining radiation dose rates at which both acute and chronic biological effects occur in different biological systems will aid in the ex-situ generation of radiation-tolerant organisms. So far, the accumulation of data on different radiation doses from Chernobyl area demonstrating various biological impacts has not been documented altogether vastly. Therefore, this review aims to document the recorded doses in CNPP over the years at which different biological changes have been observed in plants, soil, aquatic organisms, birds, and animals. A total of 72 peer-reviewed papers obtained from PubMed, Google Scholar, Scopus, and Research4life were included in this review. A few factors have come under attention in this review. Firstly, plant and soil systems combinedly showed the most published studies after the catastrophe where plants showed a higher frequency of DNA methylation in their genome to resist radiation stress. Secondly, reduced species abundance, chromosomal aberrations, increased sterility, and mortality were mostly observed in the aftermath of Chernobyl catastrophe among plants, soil, aquatic organisms, birds, and small mammals. Furthermore, major scares of data after 2018 were prominently observed. Very few studies on radiation dose levels after 2018 are available. Hence, a major research area has emerged for radiation biologists to study present radiation levels and any genetic changes in the recent generation of the original victim species. This will help provide a standard dataset that can act as a reference resource for radiation biologists and future research on the impact of both acute and chronic radiation on the different biological systems. [ABSTRACT FROM AUTHOR]

Aims: The study aimed to investigate the role of miR‐146a‐5p in osteogenesis of hPDLSCs irradiated with low‐energy red LEDs. Methods: After irradiation with 5 J/cm2 red LED, miR‐146a‐5p expression was detected by real‐time quantitative polymerase chain reaction (RT‐qPCR), and osteogenic markers expression was determined by RT‐qPCR and Western blotting. Alkaline phosphatase (ALP) activity was assessed by ALP staining, and mineralization was assessed by Alizarin Red staining, respectively. Lentiviral vectors were designed to regulate miR‐146a‐5p expression. Dual‐luciferase reporter assay was performed to confirm the targeted relationship between miR‐146a‐5p and MAPK1. Short hairpin RNA (shRNA) was used to regulate MAPK1 expression. Results: RT‐qPCR and western blotting revealed that 5 J/cm2 irradiation elevated the levels of the osteogenic markers osterix (OSX) and bone sialoprotein (BSP) in hPDLSCs. miR‐146a‐5p is downregulated in hPDLSCs under the low‐energy red LED light irradiation. miR‐146a‐5p underexpression markedly promoted the osteogenic potential of hPDLSCs. miR‐146a‐5p targeted MAPK1. 5 J/cm2 red LED irradiation rescued the inhibitory effects of upregulated miR‐146a‐5p on osteogenic differentiation, and the positive influence of red LED irradiation could be reversed by downregulated MAPK1. Conclusion: These findings confirm that miR‐146a‐5p is involved in the effect of LED irradiation on the osteogenic differentiation of hPDLSCs by targeting MAPK1. Red LED irradiation may be a potential clinical adjunct therapy for periodontal regeneration. [ABSTRACT FROM AUTHOR]

Objectives: An excessive and abrupt increase in cerebral blood flow may cause blood vessel damage, leading to stroke. Therefore, appropriate methods to immediately regulate blood flow velocity are important. Through an analysis of 31 healthy adults, we therefore investigated whether stimulating the common carotid artery (CCA) using transcutaneous electrical nerve stimulation (TENS) could modulate blood flow velocity in the CCA. Methods: Three stimulation intensities (below-threshold, threshold, and above-threshold) were applied in a random order. Blood velocity changes were examined by the measurement of peak systolic velocity (PSV) with Doppler ultrasound before, during, and after TENS stimulation. To evaluate arterial stiffness, pulse wave velocity (PWV) was calculated using CCA diameter, and blood pressure was measured before and after stimulation. Results: PSV changes in the below-threshold level were significant (p = 0.028). The PSV after below-threshold stimulation was significantly decreased by 2.23% compared to that before stimulation (p = 0.031). PWV showed no significant differences; however, a nonsignificant increase was observed immediately after stimulation only in the above-threshold condition. Above-threshold stimulation can increase vascular tone by activating the sympathetic nerve, possibly triggering vasoconstriction. Conclusions: A decrease in blood flow velocity may not be expected upon the above-threshold stimulation. In contrast, the below-threshold stimulation immediately reduces blood flow velocity, without significantly affecting hemodynamic function, such as arterial flexibility. Therefore, this short-term and low electrical stimulation technique can help to lower vascular resistance and prevent vascular damage from rapid blood flow velocity. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusion Ultra‐high dose rate irradiation (≥40 Gy/s, FLASH) has been shown to reduce normal tissue toxicity, while maintaining tumor control compared to conventional dose‐rate radiotherapy. The radiolytic oxygen (O2) depletion (ROD) resulting from FLASH has been proposed to explain the normal tissue protection effect; however, in vivo experiments have not confirmed that FLASH induced global tissue hypoxia. Nonetheless, the experiments reported are based on volume‐averaged measurement, which have inherent limitations in detecting microscopic phenomena, including the potential preservation of stem cells niches due to local FLASH‐induced O2 depletion. Computational modeling offers a complementary approach to understand the ROD caused by FLASH at the microscopic level.We developed a comprehensive model to describe the spatial and temporal dynamics of O2 consumption and transport in response to irradiation in vivo. The change of oxygen enhancement ratio (OER) was used to quantify and investigate the FLASH effect as a function of physiological and radiation parameters at microscopic scale.We considered time‐dependent O2 supply and consumption in a 3D cylindrical geometry, incorporating blood flow linking the O2 concentration ([O2]) in the capillary to that within the tissue through the Hill equation, radial and axial diffusion of O2, metabolic and zero‐order radiolytic O2 consumption, and a pulsed radiation structure. Time‐evolved distributions of [O2] were obtained by numerically solving perfusion‐diffusion equations. The model enables the computation of dynamic O2 distribution and the relative change of OER (δROD) under various physiological and radiation conditions in vivo.Initial [O2] level and the subsequent changes during irradiation determined δROD distribution, which strongly depends on physiological parameters, i.e., intercapillary spacing, ultimately determining the tissue area with enhanced radioresistance. We observed that the δROD/FLASH effect is affected by and sensitive to the interplay effect among physiological and radiation parameters. It renders that the FLASH effect can be tissue environment dependent. The saturation of FLASH normal tissue protection upon dose and dose rate was shown. Beyond ∼60 Gy/s, no significant decrease in radiosensitivity within tissue region was observed. In turn, for a given dose rate, the change of radiosensitivity became saturated after a certain dose level. Pulse structures with the same dose and instantaneous dose rate but with different delivery times were shown to have distinguishable δROD thus tissue sparing, suggesting the average dose rate could be a metric assessing the FLASH effect and demonstrating the capability of our model to support experimental findings.On a macroscopic scale, the modeling results align with the experimental findings in terms of dose and dose rate thresholds, and it also indicates that pulse structure can vary the FLASH effect. At the microscopic level, this model enables us to examine the spatially resolved FLASH effect based on physiological and irradiation parameters. Our model thus provides a complementary approach to experimental methods for understanding the underlying mechanism of FLASH radiotherapy. Our results show that physiological conditions can potentially determine the FLASH efficacy in tissue protection. The FLASH effect may be observed under optimal combination of physiological parameters, not limited to radiation conditions alone. [ABSTRACT FROM AUTHOR]

AbstractThis study investigates drug-loaded liposomes designed for controlled release under ionizing radiation to refine cancer treatment precision. Liposomes as carriers enable targeted chemotherapy delivery, reducing healthy tissue damage risk. Liposomes containing poly- or mono-unsaturated fatty acids and various sensitizing agents were assessed for responsiveness to UV light and γ photon irradiation including rose bengal (RB), protoporphyrin IX (PPIX), verteporfin (VP), cercosporin (CERC) and hypericin (HYP). Carboxyfluorescein (CF) was used as a surrogate for drug release measurements. VP and PPIX induced rapid drug release and lipid peroxidation under UV light, while RB prompted quick drug release under UV light and a modest immediate release under γ irradiation, eventually reaching full release a few hours after irradiation, demonstrating dose-dependent effects. Smaller liposomes displayed accelerated release, emphasizing size-dependent kinetics. In vitro analyses evaluated radiosensitizing effects of RB-loaded liposomes. Clonogenic assays indicated that RB-filled liposomes had minimal direct radiobiological effects but increased indirect radiation damage, as shown by the curvature of the cell survival curve. Our study sheds light on factors influencing liposomal drug release under ionizing radiation, spotlighting RB as a promising radiosensitizer requiring further investigation for cancer therapy potential. [ABSTRACT FROM AUTHOR]

The long‐term impacts of radiocontaminants (and the associated risks) for ecosystems are still subject to vast societal and scientific debate while wildlife is chronically exposed to various sources and levels of either environmental or anthropogenic ionizing radiation from the use of nuclear energy. The present study aimed to assess induced phenotypical responses in both male and female gammarids after short‐term continuous γ‐irradiation, acting as a typical well‐characterized genotoxic stressor that can interact directly with living matter. In particular, we started characterizing the effects using standardized measurements for biological effects on few biological functions for this species, especially feeding inhibition tests, molting, and reproductive ability, which have already been proven for chemical substances and are likely to be disturbed by ionizing radiation. The results show no significant differences in terms of the survival of organisms (males and females), of their short‐term food consumption which is linked to the general health status (males and females), and of the molting cycle (females). In contrast, exposure significantly affected fecundity (number of embryos produced) at the highest dose rates for irradiated females (51 mGy h–1) and males (5 and 51 mGy h–1). These results showed that, in gammarids, reproduction, which is a critical endpoint for population dynamics, is the most radiosensitive phenotypic endpoint, with significant effects recorded on male reproductive capacity, which is more sensitive than in females. Environ Toxicol Chem 2024;43:2071–2079. © 2024 SETAC [ABSTRACT FROM AUTHOR]

Aim: The risks to public health of radiofrequency signals emitted by mobile phones, an indispensable part of our daily lives, have begun to be questioned. For this reason, the magnetic field created by a third-generation mobile phone was applied to the embryos obtained by in vitro embryo culture technique during the organogenesis period of the rat embryo and its effect on development was examined. Material and Method: In our study, 20 adult female rats weighing between 200-300 g and 30 male Wistar albino rats weighing over 300 g were used. The developmental morphology of embryos from the control and experimental groups exposed to magnetic fields for different periods (24 hours, 48 hours) was evaluated. Results: When the morphological score, yolk sac diameter, crown-rump length and number of somites of embryos exposed to magnetic fields for different periods were compared, the experimental groups regressed compared to the control group. Conclusion: As a result, it was shown that developmental delays and deformities may occur in embryos depending on the duration of exposure to the magnetic field. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the radiation knowledge and awareness levels of healthcare workers working in a single center in Mogadishu, Somalia, in terms of age, gender and education levels of the participants.Materials and methods: The research involved 274 healthcare professionals, comprising volunteer physician and other healthcare personnel working at the Somali-Turkey Recep Tayyip Erdoğan Training and Research Hospital in Mogadishu. The face-to-face questionnaire consists of 13 questions covering radiation-sensitive or resistant tissues, radiation status of medical imaging devices, biological effects of radiation, ionizing and non-ionizing radiation symbols and radiation protection principles. The study was limited to the health personnel in the hospital. The survey had 274 participants, comprising 126 (46%) women and 148 (54%) men. Of these, 82 (29.9%) were physicians and 192 (70.1%) were other healthcare professionals.Results: It was found that health workers under the age of thirty demonstrated a significantly higher level of knowledge about radiation protection principles than their counterparts over the age of thirty (p = 0.003). Similarly, it was observed that the level of awareness regarding the extent of knowledge about radiation protection was higher in health workers under thirty years of age than in those over thirty years of age (p: 0.001). It was found to be statistically significant that males were more aware of the potential harms of radiation than females (p: 0.004). It was found to be statistically significant that men were more aware of the radiation content of mammography and X-ray imaging methods than women (p: 0.002 and p: 0.029, respectively).Conclusions: To enhance the number of healthcare professionals in Mogadishu, Somalia, who are aware of the risks associated with radiation and the methods for its mitigation, it was postulated that a comprehensive radiation information and awareness training program could be beneficial. [ABSTRACT FROM AUTHOR]

Objectives: Olfactory dysfunction is an overlooked adverse effect of radiation therapy. This study is designed to find the effect of radiation therapy on olfactory function in head and neck malignancy excluding tumors of nose and nasopharynx and correlate the olfactory changes with the radiotherapy dose. Method: This prospective observational study was done over a 2-year period in 34 participants with head and neck malignancies who underwent radiation therapy (RT). The participants olfaction was evaluated subjectively with Italian Nose Obstruction Symptom Evaluation (I-NOSE) scale and objectively by a modified I-Smell test which included an olfactory identification score and an olfactory threshold score at 5 time points. The beginning of RT (T 0), at 2 weeks of RT(T 1), end of RT (T 2), 1 month follow-up (T 3), and 3-month follow-up (T 4). The near maximum dose to the nasal cavity (D 2%) and mean dose to the nasal cavity (D mean) were calculated for all participants and correlated with olfactory function. Results: A total of 34 patients with head neck malignancy were recruited. The median I-NOSE score reached maximum at the end of radiation and decreased to baseline at 3 months follow-up (P <.001). The olfactory identification score, olfactory threshold score, and median combined olfactory score showed a significant decrease at the end of radiation therapy compared to Pre-radiation therapy values. There was a significant but incomplete recovery in the 3-month follow-up period (P <.001). Conclusion: There was a significant deterioration in quality of life for olfaction, olfactory identification, and olfactory threshold at the completion of radiotherapy. At 3 months follow-up, though there was no complete recovery of olfaction, it did not have an adverse effect on the quality of life. [ABSTRACT FROM AUTHOR]

The concept of radiation-induced clustered damage in DNA has grown over the past several decades to become a topic of considerable interest across the scientific disciplines involved in studies of the biological effects of ionizing radiation. This paper, prepared for the 70th anniversary issue of Radiation Research, traces historical development of the three main threads of physics, chemistry, and biochemical/cellular responses that led to the hypothesis and demonstration that a key component of the biological effectiveness of ionizing radiation is its characteristic of producing clustered DNA damage of varying complexities. The physics thread has roots that started as early as the 1920s, grew to identify critical nanometre-scale clusterings of ionizations relevant to biological effectiveness, and then, by the turn of the century, had produced an extensive array of quantitative predictions on the complexity of clustered DNA damage from different radiations. Monte Carlo track structure simulation techniques played a key role through these developments, and they are now incorporated into many recent and ongoing studies modelling the effects of radiation. The chemistry thread was seeded by water-radiolysis descriptions of events in water as radical-containing "spurs," demonstration of the important role of the hydroxyl radical in radiation-inactivation of cells and the difficulty of protection by radical scavengers. This led to the concept and description of locally multiply damaged sites (LMDS) for DNA double-strand breaks and other combinations of DNA base damage and strand breakage that could arise from a spur overlapping, or created in very close proximity to, the DNA. In these ways, both the physics and the chemistry threads, largely in parallel, put out the challenge to the experimental research community to verify these predictions of clustered DNA damage from ionizing radiations and to investigate their relevance to DNA repair and subsequent cellular effects. The third thread, biochemical and cell-based research, responded strongly to the challenge by demonstrating the existence and biological importance of clustered DNA damage. Investigations have included repair of a wide variety of defined constructs of clustered damage, evaluation of mutagenic consequences, identification of clustered base-damage within irradiated cells, and identification of co-localization of repair complexes indicative of complex clustered damage after high-LET irradiation, as well as extensive studies of the repair pathways involved in repair of simple double-strand breaks. There remains, however, a great deal more to be learned because of the diversity of clustered DNA damage and of the biological responses. [ABSTRACT FROM AUTHOR]

At the dawn of the 20th Century, the underlying chemistry that produced the observed effects of ionizing radiation, e.g., X rays and Radium salts, on aqueous solutions was either unknown or restricted to products found postirradiation. For example, the Curies noted that sealed aqueous solutions of Radium inexplicably decomposed over time, even when kept in the dark. By 1928 there were numerous papers describing the phenomenological effects of ionizing radiation on a wide variety of materials, including the irradiated hands of early radiologists. One scientist who became intensely interested in these radiation effects was Hugo Fricke (Fricke Dosimetry) who established a laboratory in 1928 dedicated to studies on chemical effects of radiation, the results of which he believed were necessary to understand observed radiobiological effects. In this Platinum Issue of Radiation Research (70 years of continuous publication), we present the early history of the development of radiation chemistry and its contributions to all levels of mechanistic radiobiology. We summarize its development as one of the four disciplinary pillars of the Radiation Research Society and its Journal, Radiation Research, founded during the period 1952–1954. In addition, the work of scientists who contributed substantially to the discipline of Radiation Chemistry and to the birth, life and culture of the Society and its journal is presented. In the years following 1954, the increasing knowledge about the underlying temporal and spatial properties of the species produced by various types of radiation is summarized and related to its radiobiology and to modern technologies (e.g., pulsed radiolysis, electron paramagnetic resonance) which became available as the discipline of radiation chemistry developed. A summary of important results from these studies on Radiation Chemistry/Biochemistry in the 20th and 21st Century up to the present time is presented. Finally, we look into the future to see what possible directions radiation chemistry studies might take, based upon promising current research. We find at least two possible directions that will need radiation chemistry expertise to ensure proper experimental design and interpretation of data. These are FLASH radiotherapy, and mechanisms underlying the effects of low doses of radiation delivered at low dose rates. Examples of how radiation chemists could provide beneficial input to these studies are provided. [ABSTRACT FROM AUTHOR]

In vitro and in vivo observations accumulated over several decades have firmly shown that the biological effects of ionizing radiation can spread from irradiated cells/tissues to non-targeted cells/tissues. Redox-modulated intercellular communication mechanisms that include a role for secreted factors and gap junctions, can mediate these non-targeted effects. Clearly, the expression of such effects and their transmission to progeny cells has implications for issues related to radiation protection. Their elucidation is also relevant towards enhancing the efficacy of cancer radiotherapy and reducing its impact on the development of normal tissue toxicities. In addition, the study of non-targeted effects is pertinent to our basic understanding of intercellular communications under conditions of oxidative stress. This review will trace the history of non-targeted effects of radiation starting with early reports of abscopal effects which described radiation induced effects in tissues distant from the site of radiation exposure. A related effect involved the production of clastogenic factors in plasma following irradiation which can induce chromosome damage in unirradiated cells. Despite these early reports suggesting non-targeted effects of radiation, the classical paradigm that a direct deposition of energy in the nucleus was required still dominated. This paradigm was challenged by papers describing radiation induced bystander effects. This review will cover mechanisms of radiation-induced bystander effects and the potential impacts on radiation protection and radiation therapy. [ABSTRACT FROM AUTHOR]

Radiation cytogenetics has a rich history seldom appreciated by those outside the field. Early radiobiology was dominated by physics and biophysical concepts that borrowed heavily from the study of radiation-induced chromosome aberrations. From such studies, quantitative relationships between biological effect and changes in absorbed dose, dose rate and ionization density were codified into key concepts of radiobiological theory that have persisted for nearly a century. This review aims to provide a historical perspective of some of these concepts, including evidence supporting the contention that chromosome aberrations underlie development of many, if not most, of the biological effects of concern for humans exposed to ionizing radiations including cancer induction, on the one hand, and tumor eradication on the other. The significance of discoveries originating from these studies has widened and extended far beyond their original scope. Chromosome structural rearrangements viewed in mitotic cells were first attributed to the production of breaks by the radiations during interphase, followed by the rejoining or mis-rejoining among ends of other nearby breaks. These relatively modest beginnings eventually led to the discovery and characterization of DNA repair of double-strand breaks by non-homologous end joining, whose importance to various biological processes is now widely appreciated. Two examples, among many, are V(D)J recombination and speciation. Rapid technological advancements in cytogenetics, the burgeoning fields of molecular radiobiology and third-generation sequencing served as a point of confluence between the old and new. As a result, the emergent field of "cytogenomics" now becomes uniquely positioned for the purpose of more fully understanding mechanisms underlying the biological effects of ionizing radiation exposure. [ABSTRACT FROM AUTHOR]

\nPlain Language SummaryBreast cancer has been recognized as the most common cancer affecting women. Extremely low-frequency electromagnetic field (ELF-EMF) exposure can influence cellular activities such as cell-cell junctions and metastasis. However, more research is required to determine these fields’ underlying mechanisms of action. Since cadherin switching is an important process during EMT (epithelial-mesenchymal transition), in this study, cadherin switching was regarded as one of the probable mechanisms of the effect of ELF-EMFs on metastasis suppression. For five days, breast cells received a 1 Hz, 100mT ELF-EMF (2 h/day). Cell invasion and migration were assessed in vitro by the Scratch wound healing assay and Transwell culture chambers. The expression of E- and N-cadherin was assessed using real-time PCR, western blotting, and Immunocytochemistry. ELF-EMF dramatically reduced the migration and invasion of MDA-MB 231 malignant cells compared to sham exposure, according to the results of the scratch test and the Transwell invasion test. The mRNA and protein expression levels of E-cadherin showed an increase, while the N-cadherin expression was found with a decrease, in MDA-MB231 cells receiving 1 Hz EMF compared to sham exposure. E-cadherin’s mRNA and protein expression levels were enhanced in MCF10A cells receiving 1 Hz EMF compared to sham exposure. ELF-EMF can be used as a method for the multifaceted treatments of invasive breast cancer.Breast cancer (BC) is one of the main reasons for cancer-related mortality among the female population. Despite the huge efforts made to treat BC, metastasis has remained one of the most complicated and hardly manageable problems. Extremely low-frequency electromagnetic fields (ELF-EMFs) are low-energy non-ionizing radiation with several biological effects whose influence on living organisms has been recently explored. However, the mechanisms of action of these electromagnetic fields have not been fully understood. For five days, breast cells received a 1Hz, 100mT ELF-EMF (2h/day). Cell invasion and migration were assessed in vitro by the Scratch wound healing assay and Transwell culture chambers. The expression of E- and N-cadherin was assessed using real-time PCR, western blotting, and Immunocytochemistry. ELF-EMF dramatically reduced the migration and invasion of MDA-MB 231 malignant cells compared to sham exposure, according to the scratch test results and the Transwell invasion test. The mRNA and protein expression levels of E-cadherin showed an increase, while the N-cadherin expression was decreased, in MDA-MB231 cells receiving 1Hz EMF compared to sham exposure. The present report can be considered as a preliminary study for future investigations on ELF-EMF that recommends ELF-EMF can be used as a method for the multifaceted treatment of invasive BC which requires further studies. [ABSTRACT FROM AUTHOR]

As a model organism for space biology experiments, Caenorhabditis elegans (C. elegans) has low demand for life support and strong resistance to unfavorable environments, making experimentation with C. elegans relatively easy and cost-effective. Previously, C. elegans has been flown in several spaceflight investigations, but there is still an urgent need for analytical platforms enabling on-orbit automated monitoring of multiple phenotypes of worms, such as growth and development, movement, changes of biomarkers, etc. To solve this problem, we presented a fully integrated microfluidic system (WormSpace μ-TAS) with an arrayed microfluidic chip (WormChip-4.8.1) and a replaceable microfluidic module (WormChip cartridge), which was compatible with the experimental facility on the China Space Station (CSS). By adopting technologies of programmed fluid control based on liquid medium CeMM as well as multi-function imaging with a camera mounted on a three-dimensional (3D) transportation stage, automated and long-term experimentation can be performed for on-chip multi-strain culturing and bright-field and fluorescence imaging of C. elegans at the single-worm level. The presented WormSpace μ-TAS enabled its successful application on the CSS, achieving flight launch of the sample unit (WormChip cartridge) at low temperature (controlled by a passive thermal case at 12 °C), automated 30-day cultivation of 4 strains of C. elegans, on-orbit monitoring of multiple phenotypes (growth and development, movement, and changes of fluorescent protein expression) at the single worm-level, on-chip fixation of animals at the end of the experiment and returning the fixed samples to earth. In summary, this study presented a verified microfluidic system and experimental protocols for automated on-chip multi-strain culturing and multi-function imaging of C. elegans at the single-worm level on the CSS. The WormSpace μ-TAS will provide a novel experimental platform for the study of biological effects of space radiation and microgravity, and for the development of protective drugs. [ABSTRACT FROM AUTHOR]

Simple Summary: Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer therapy that uses NIR light and conjugates of a tumor-targeting monoclonal antibody and phthalocyanine dye. In clinical practice, frontal and cylindrical diffusers are used for NIR illumination. However, the light illumination of a narrow space is technically difficult with such diffusers. Therefore, we evaluated the usefulness of a lateral illumination system using lateral emitting laser (LEL) fiber. The LEL fiber was capable of illuminating only a certain area in a lateral direction. NIR-PIT with an LEL fiber showed cytotoxic effects in vitro and suppressed tumor proliferation in vivo. Moreover, the LEL fiber delivered NIR light to an entire tumor more uniformly than a frontal diffuser in a narrow-space model. These results suggest that the LEL fiber can be used for NIR-PIT and is suitable for NIR light illumination in a narrow space. Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer therapy that uses NIR light and conjugates of a tumor-targeting monoclonal antibody and phthalocyanine dye. In clinical practice, frontal and cylindrical diffusers are the only options for NIR illumination. However, illumination in a narrow space is technically difficult with such diffusers. Therefore, we evaluated a lateral illumination system using a lateral emitting laser (LEL) fiber. The LEL fiber illuminated a certain area in a lateral direction. NIR-PIT with an LEL fiber reduced luciferase activity in a light-dose-dependent manner in A431-GFP-luc cells in vitro and significantly suppressed tumor proliferation in a xenograft mouse model. To evaluate the usefulness of the LEL fiber in the illumination of a narrow space, a tumor was illuminated from the inside of a cylinder, mimicking a narrow space, and the fluorescence intensity in the tumor was monitored. In the frontal diffuser, NIR light was unevenly delivered and little light reached a distal tumor area from the illuminated side. By contrast, the LEL fiber allowed a uniform illumination of the entire tumor, and a loss of fluorescence was observed even in distal areas. These findings suggested that the LEL fiber can be used for NIR-PIT and is suitable for NIR light illumination in a narrow space. [ABSTRACT FROM AUTHOR]

Space radiobiology, a multidisciplinary field investigating the biological effects of ionizing radiation on astronauts during space missions, plays a pivotal role in understanding and mitigating health risks associated with Galactic Cosmic Rays and solar radiation. The INFN Roma Sapienza Alpha Magnetic Spectrometer research group has been at the forefront of advancing research in this critical domain over the last five years. This presentation highlights the interdisciplinary approach employed in our research activities, emphasizing the collaborative efforts that have significantly contributed to the assessment of health risks induced by GCR radiation exposure. Our research endeavors delve into dose-effects models, establishing crucial relationships and providing a theoretical framework for modelling non-target effects resulting from space radiation—a paramount consideration in evaluating carcinogenic risks associated with deep space exploration. Furthermore, the discussion sheds light on the roles played by data collected from astroparticle experiments operating in space, with a specific focus on the mid and heavy nuclei components of space radiation. An integral aspect of our recent initiatives involves collaboration with esteemed research institutions, notably the National Institute for Laser, Plasma, and Radiation Physics (INFLPR) in Bucharest. This collaborative effort aims to explore the potential of reproducing space radiation conditions through ground experiments, employing innovative Laser Plasma Accelerators and the launch of a research topic collection dedicated to space radiobiology. This initiative further amplifies our commitment to advancing knowledge in this multidisciplinary field. [ABSTRACT FROM AUTHOR]

Because reactive oxygen species are involved in the regulation of biological rhythms, we hypothesized that intra-annual variability of seed progeny quality at low doses of ionizing radiation (LDIRs) would differ from that of background plants. We conducted 12 consecutive experiments using the roll culture method by germinating seeds (monthly for 3 weeks) of six herbaceous plant species (Bromus inermis, Geum aleppicum, Plantago major, Rumex confertus, Silene latifolia, and Taraxacum officinale) growing under conditions of chronic radiation in the East Ural Radioactive Trace (EURT). We assessed physiological (seed viability and abnormality frequency) and biochemical (low-molecular-weight antioxidants, LMWAs) parameters of seedlings. Total absorbed dose rates of maternal plants (TADRplants) and seed embryos (TADRseeds) in the EURT exceeded background levels by 1–3 and 1–2 orders of magnitude, respectively. Nonlinear dependencies on TADR were mainly characteristic of physiological and biochemical parameters. For most populations of the studied species (B. inermis, G. aleppicum, R. confertus, and S. latifolia), seedling survival and root length decreased in the autumn–winter period, while the frequency of abnormal seedlings increased. The content of LMWAs could be ranked as R. confertus > B. inermis > G. aleppicum > S. latifolia, in good agreement with the presence of anthocyanin pigmentation in the plants. The lowest synthesis of antioxidants in seedlings was observed in winter. A high LMWA content promoted growth and reduced the frequency of abnormal seedlings. These results underscore a multistage nature of the impact of LDIRs on intra-annual biological rhythms in plants. High heterogeneity in reference group 'wild grasses' and diversity of their radiobiological effects should help to develop methods of radiation protection for natural ecosystems and facilitate approaches used by the International Commission on Radiological Protection. Absorbed dose rates for six plant species in the East Ural Radioactive Trace (EURT) area range from 0.11 to 73.89 µGy h−s (plants) and 0.11 to 6.88 µGy h−s (seed embryos). Intra-annual rhythms of physiological and biochemical parameters in the EURT zone differ from those in background seedlings. Plants in the EURT area exhibit a wide range of trait variability, asynchrony of the manifestation of the effects, nonlinear dose–response relations, and hormesis. A high content of low-molecular-weight antioxidants (LMWAs) is associated with low frequency of developmental abnormalities and high viability of seed progeny. [ABSTRACT FROM AUTHOR]

The ionizing radiation with high linear energy transfer (LET), such as a heavy ion beam, induces more serious biological effects than low LET ones, such as gamma- and X-rays. This indicates a difference in the DNA damage produced by low and high LET radiations and their biological effects. We have been studying the differences in DNA damage produced by gamma-rays and carbon ion beams. Therefore, we analyze mutations induced by both ionizing radiations to discuss the differences in their biological effects in this study. pUC19 plasmid DNA was irradiated by carbon ion beams in the solution containing 1M dimethyl sulfoxide to mimic a cellular condition. The irradiated DNA was cloned in competent cells of Escherichia coli. The clones harboring some mutations in the region of lacZα were selected, and the sequence alterations were analyzed. A one-deletion mutation is significant in the carbon-irradiated DNA, and the C:G↔T:A transition is minor. On the other hand, the gamma-irradiated DNA shows mainly G:C↔T:A transversion. These results suggest that carbon ion beams produce complex DNA damage, and gamma-rays are prone to single oxidative base damage, such as 8-oxoguanine. Carbon ion beams can also introduce oxidative base damage, and the damage species is 5-hydroxycytosine. This was consistent with our previous results of DNA damage caused by heavy ion beams. We confirmed the causal DNA damage by mass spectrometry for these mutations. [ABSTRACT FROM AUTHOR]

This scientific paper focuses on the treatment of breast cancer, one of the most common cancers among women. Despite increased awareness and the popularity of screening tests, statistics indicate a significant rise in incidence. The paper presents breast-conserving treatment methods, including brachytherapy, as a modern technique with promising outcomes. It describes the physical properties of ionizing radiation used in brachytherapy, discussing the photoelectric effect, Compton effect, and the phenomenon of pair production. The paper then delves into the biological effects of ionizing radiation, emphasizing the dependence on the cell cycle phase. It highlights lethal, sublethal, and potentially lethal cellular damage, categorizing the effects of radiation interaction into early and late responses. The discussion transitions to the application of brachytherapy in breast cancer treatment, focusing on various techniques such as LDR, PDR, and HDR. The paper provides a detailed description of brachytherapy's use in breast-conserving treatment, considering contraindications, treatment planning, and Accelerated Partial Breast Irradiation (APBI) techniques. The radioisotopes used in brachytherapy are also presented, with special attention to Iridium-192. The physical and practical aspects related to this isotope are discussed, along with other commonly used radioisotopes such as Cesium-137, Cobalt-60, and Strontium-90. The paper concludes with a summary, emphasizing the significance of brachytherapy in breast cancer treatment and outlining its prospects for development. The authors highlight precision and shortened therapy duration. Aim of the study The following paper aims to present a review of current knowledge regarding brachytherapy in the treatment of breast cancer and the treatment outcomes associated with this method. The main goal is to raise awareness among healthcare professionals about current issues with improvement of breast cancer treatment procedures based on brachytherapy. Materials and methods This article presents the current state of knowledge about brachytherapy for breast cancer, as found in various scientific articles. The following English keywords and their Polish equivalents were used to search Google Scholar's medical databases: brachytherapy, conservative treatment, breast cancer, BT, MammoSite. The most relevant articles on the subject were selected. [ABSTRACT FROM AUTHOR]

Simple Summary: Tritium is one of the most significant fuels in fusion reactors and it also represents an important radioactive isotope discharged into the environment from nuclear power plants. The risk of tritium should be answered before the construction of fusion reactors. Mitochondria have been identified as a potentially sensitive target for investigating low-dose/low-dose-rate radiation effects, with extensive experimental results obtained using X-ray irradiation. In this manuscript, we experimentally studied the impact of mitochondrial function regulation on tritium radiation biological effects. It was found that there was no significant difference in cell viability induced by different doses. However, the results of ATP levels showed a considerable difference after irradiation at a dose of 500 mGy by tritium β-rays compared to the sham-irradiated sample, while the levels obtained with X-ray irradiation were almost identical to the sham-irradiated sample. In contrast, ATP levels for both tritium β-rays and X-rays at a dose of 1.0 Gy showed little difference compared to the sham-irradiated sample. This suggests that mitochondria might be a potentially sensitive target for investigating tritium β-ray irradiation effects, and they are helpful for the risk evaluation of tritium for the development of fusion energy. The effects of tritium at low doses and low dose rates have received increasing attention due to recent developments in fusion energy and the associated risks of tritium releases into the environment. Mitochondria have been identified as a potential candidate for studying the effects of low-dose/low-dose-rate radiation, with extensive experimental results obtained using X-ray irradiation. In this study, irradiation experiments were conducted on normal B-lymphoblastoid cells using HTO at varying doses. When compared to X-ray irradiation, no significant differences in cell viability induced by different doses were observed. However, the results of ATP levels showed a significant difference between the irradiated sample at a dose of 500 mGy by tritium beta-rays and the sham-irradiated sample, while the levels obtained with X-ray irradiation were almost identical to the sham-irradiated sample. In contrast, ATP levels for both tritium beta-rays and X-rays at a dose of 1.0 Gy showed minimal differences compared to the sham-irradiated sample. Furthermore, distinct effects at 500 mGy were also confirmed in both ROS levels and apoptosis results obtained through tritium beta-ray irradiation. This suggests that mitochondria might be a potential sensitive target for investigating the effects of tritium beta-ray irradiation. [ABSTRACT FROM AUTHOR]

Brachytherapy utilizes a multitude of radioactive sources and treatment techniques that often exhibit widely different spatial and temporal dose delivery patterns. Biophysical models, capable of modeling the key interacting effects of dose delivery patterns with the underlying cellular processes of the irradiated tissues, can be a potentially useful tool for elucidating the radiobiological effects of complex brachytherapy dose delivery patterns and for comparing their relative clinical effectiveness. While the biophysical models have been used largely in research settings by experts, it has also been used increasingly by clinical medical physicists over the last two decades. A good understanding of the potentials and limitations of the biophysical models and their intended use is critically important in the widespread use of these models. To facilitate meaningful and consistent use of biophysical models in brachytherapy, Task Group 267 (TG‐267) was formed jointly with the American Association of Physics in Medicine (AAPM) and The Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology (GEC‐ESTRO) to review the existing biophysical models, model parameters, and their use in selected brachytherapy modalities and to develop practice guidelines for clinical medical physicists regarding the selection, use, and interpretation of biophysical models. The report provides an overview of the clinical background and the rationale for the development of biophysical models in radiation oncology and, particularly, in brachytherapy; a summary of the results of literature review of the existing biophysical models that have been used in brachytherapy; a focused discussion of the applications of relevant biophysical models for five selected brachytherapy modalities; and the task group recommendations on the use, reporting, and implementation of biophysical models for brachytherapy treatment planning and evaluation. The report concludes with discussions on the challenges and opportunities in using biophysical models for brachytherapy and with an outlook for future developments [ABSTRACT FROM AUTHOR]

(1) Background: DNA damage is of great importance in the understanding of the effects of ionizing radiation. Various types of DNA damage can result from exposure to ionizing radiation, with clustered types considered the most important for radiobiological effects. (2) Methods: The code RITRACKS (Relativistic Ion Tracks), a program that simulates stochastic radiation track structures, was used to simulate DNA damage by photons and ions spanning a broad range of linear energy transfer (LET) values. To perform these simulations, the transport code was modified to include cross sections for the interactions of ions or electrons with DNA and amino acids for ionizations, dissociative electron attachment, and elastic collisions. The radiochemistry simulations were performed using a step-by-step algorithm that follows the evolution of all particles in time, including reactions between radicals and DNA structures and amino acids. Furthermore, detailed DNA damage events, such as base pair positions, DNA fragment lengths, and fragment yields, were recorded. (3) Results: We report simulation results using photons and the ions 1H+, 4He2+, 12C6+, 16O8+, and 56Fe26+ at various energies, covering LET values from 0.3 to 164 keV/µm, and performed a comparison with other codes and experimental results. The results show evidence of DNA protection from damage at its points of contacts with histone proteins. (4) Conclusions: RITRACKS can provide a framework for studying DNA damage from a variety of ionizing radiation sources with detailed representations of DNA at the atomic scale, DNA-associated proteins, and resulting DNA damage events and statistics, enabling a broader range of future comparisons with experiments such as those based on DNA sequencing. [ABSTRACT FROM AUTHOR]

Details of excitation and ionization acts hide a description of the biological effects of charged particle traversal through living tissue. Nanodosimetry enables the introduction of novel quantities that characterize and quantify the particle track structure while also serving as a foundation for assessing biological effects based on this quantification. This presents an opportunity to enhance the planning of charged particle radiotherapy by taking into account the ionization detail. This work uses Monte Carlo simulations with Geant4-DNA code for a wide variety of charged particles and their radiation qualities to analyze the distribution of ionization cluster sizes within nanometer-scale volumes, similar to DNA diameter. By correlating these results with biological parameters extracted from the PIDE database for the V79 cell line, a novel parameter R 2 based on ionization details is proposed for the evaluation of radiation quality in terms of biological consequences, i.e., radiobiological cross section for inactivation. By incorporating the probability p of sub-lethal damage caused by a single ionization, we address limitations associated with the usually proposed nanodosimetric parameter F k for characterizing the biological effects of radiation. We show that the new parameter R 2 correlates well with radiobiological data and can be used to predict biological outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Intraoperative radiation therapy (IORT) delivers a single accelerated radiation dose to the breast tumor bed during breast-conserving surgery (BCS). The synergistic biologic effects of simultaneous surgery and radiation remain unclear. This study explores the cellular and molecular changes induced by IORT in the tumor microenvironment and its impact on the immune response modulation. Methods: Patients with hormone receptor (HR)-positive/HER2-negative, ductal carcinoma in situ (DCIS), or early-stage invasive breast carcinoma undergoing BCS with margin re-excision were included. Histopathological evaluation and RNA-sequencing in the re-excision tissue were compared between patients with IORT (n=11) vs. non-IORT (n=11). Results: Squamous metaplasia with atypia was exclusively identified in IORT specimens (63.6%, p=0.004), mimicking DCIS. We then identified 1,662 differentially expressed genes (875 upregulated and 787 downregulated) between IORT and non-IORT samples. Gene ontology analyses showed that IORT was associated with the enrichment of several immune response pathways, such as inflammatory response, granulocyte activation, and T-cell activation (p<0.001). When only considering normal tissue from both cohorts, IORT was associated with intrinsic apoptotic signaling, response to gamma radiation, and positive regulation of programmed cell death (p<0.001). Using the xCell algorithm, we inferred a higher abundance of gd T-cells, dendritic cells, and monocytes in the IORT samples. Conclusion: IORT induces histological changes, including squamous metaplasia with atypia, and elicits molecular alterations associated with immune response Frontiers in Immunology frontiersin. and intrinsic apoptotic pathways. The increased abundance of immune-related components in breast tissue exposed to IORT suggests a potential shift towards active immunogenicity, particularly immune-desert tumors like HR-positive/ HER2-negative breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: The study aimed to analyze and determine impact of the 3D-CRT fractionation on risk of secondary cancer. Material and Methods: This study used a patient-specific anthropomorphic phantom, and radiation was performed using the Three Dimensional-Conformal Radiation Therapy Field in Field (3D-CRT FinF) technique with conventional, hypofractionation, and hyperfractionation with a dose of 200 cGy, 260 cGy, and 160 cGy in 25, 16, and 30 fractions respectively. It focused on the contralateral breast, contralateral lung, and ipsilateral lung as Organs at Risk (OAR). In addition, the Dose Volume Histogram (DVH) value, normal tissue complication probability (NTCP), and risk of secondary cancer were evaluated. Results: The results showed that the average dose value (Dmean) for ipsilateral lung with hypofractionation was smaller than conventional and hyperfractionation of 1519.8, 1826.7, and 1753.6 cGy, respectively. Furthermore, hypofractionation also reduced radiobiological effects by 50% in the ipsilateral lung with an NTCP value of 0.01% compared to conventional and hyperfractionation with a value of 0.02%. Hypofractionation reduces the risk of secondary cancer in the contralateral breast, contralateral lung, and ipsilateral lung by 16.38, 17, and 22.31% compared to conventional fractionation and 12.75, 13.54, and 21.34% compared to hyperfractionation, respectively. Conclusion: The dose profiles in OAR was smaller in treatment planning with hypofractionation. EBT3 film verification results showed that the ipsilateral lung received more doses than planned, with an insignificant difference (p>0.05). In radiobiology, the ipsilateral lung has the highest probability of complications in treatment planning with conventional fractionation and hyperfractionation. [ABSTRACT FROM AUTHOR]

Objectives: Radiation injury is common after radiotherapy for head and neck cancer. Radiotherapy can reshape the immune microenvironment and cause immunosuppression, including dysregulation of immune checkpoints (ICs). However, the relationship between oral ICs expression after radiation and the development of second primary tumors is unclear. Methods: Clinical specimens of second primary oral squamous cell carcinoma after radiotherapy (s‐OSCC) and primary OSCC (p‐OSCC) were collected. The expression and prognostic value of PD‐1, VISTA, and TIM‐3 were analyzed using immunohistochemistry. To further clarify the relationship between radiation and ICs alteration, a rat model was constructed to explore the spatiotemporal changes of ICs in the oral mucosa after radiation. Results: In carcinoma tissue, the expression of TIM‐3 was higher in s‐OSCC than in p‐OSCC, while the expression of PD‐1 and VISTA was similar between the groups. In para‐carcinoma tissue, the expression of PD‐1, VISTA, and TIM‐3 was higher in s‐OSCC. High ICs expression was associated with poor survival. In the rat model, ICs were locally upregulated in the irradiated tongue. Moreover, there was a bystander effect, in which the ICs were also upregulated in the unirradiated site. Conclusion: Radiation may upregulate ICs expression in oral mucosa and contribute to the development of s‐OSCC. [ABSTRACT FROM AUTHOR]

Simple Summary: A significant number of prostate cancers (PC) recur in patients despite treatment with chemotherapy or radiotherapy. While HOXB13 contributes to resistance to anti-androgen treatment, its role in radio resistance is unknown. Herein, we show that HOXB13 assembles at DNA damage sites and colocalizes with γH2AX at double strand breaks despite Androgen Receptor antagonism. Functionally, ablation of HOXB13 sensitizes PC cells to either radiotherapy or anti-androgen Enzalutamide as well as combination therapies. Resistance to these agents is mediated by acetylation of HOXB13 at lysine 13, which acts as an interaction module for the Switch deficient Sucrose Nonfermenting (SWI/SNF) chromatin remodeling complex. K13-acetylated HOXB13 is required for effective DNA replication following DNA damage and for the formation of nuclear puncta. Our results reveal a hitherto unknown but critical role for HOXB13 in ensuring genomic integrity in PC. Advanced localized prostate cancers (PC) recur despite chemotherapy, radiotherapy and/or androgen deprivation therapy. We recently reported HOXB13 lysine (K)13 acetylation as a gain-of-function modification that regulates interaction with the SWI/SNF chromatin remodeling complex and is critical for anti-androgen resistance. However, whether acetylated HOXB13 promotes PC cell survival following treatment with genotoxic agents is not known. Herein, we show that K13-acetylated HOXB13 is induced rapidly in PC cells in response to DNA damage induced by irradiation (IR). It colocalizes with the histone variant γH2AX at sites of double strand breaks (DSBs). Treatment of PCs with the Androgen Receptor (AR) antagonist Enzalutamide (ENZ) did not suppress DNA-damage-induced HOXB13 acetylation. In contrast, HOXB13 depletion or loss of acetylation overcame resistance of PC cells to ENZ and synergized with IR. HOXB13K13A mutants show diminished replication fork progression, impaired G2/M arrest with significant cell death following DNA damage. Mechanistically, we found that amino terminus regulates HOXB13 nuclear puncta formation that is essential for proper DNA damage response. Therefore, targeting HOXB13 acetylation with CBP/p300 inhibitors in combination with DNA damaging therapy may be an effective strategy to overcome anti-androgen resistance of PCs. [ABSTRACT FROM AUTHOR]

People are exposed to low-dose radiation in medical diagnosis, occupational, or life circumstances, but the effect of low-dose radiation on human health is still controversial. The biological effects of radiation below 100 mGy are still unproven. In this study, we observed the effects of low-dose radiation (100 mGy) on gene expression in human coronary artery endothelial cells (HCAECs) and its effect on molecular signaling. HCAECs were exposed to 100 mGy ionizing radiation at 6 mGy/h (low-dose-rate) or 288 mGy/h (high-dose-rate). After 72 h, total RNA was extracted from sham or irradiated cells for Quant-Seq 3'mRNA-Seq, and bioinformatic analyses were performed using Metascape. Gene profiling was validated using qPCR. Compared to the non-irradiated control group, 100 mGy of ionizing radiation at 6 mGy/h altered the expression of 194 genes involved in signaling pathways related to heart contraction, blood circulation, and cardiac myofibril assembly differentially. However, 100 mGy at 288 mGy/h altered expression of 450 genes involved in cell cycle-related signaling pathways, including cell division, nuclear division, and mitosis differentially. Additionally, gene signatures responding to low-dose radiation, including radiation dose-specific gene profiles (HIST1H2AI, RAVER1, and POTEI) and dose-rate-specific gene profiles (MYL2 for the low-dose-rate and DHRS9 and CA14 for the high-dose-rate) were also identified. We demonstrated that 100 mGy low-dose radiation could alter gene expression and molecular signaling pathways at the low-dose-rate and the high-dose-rate differently. Our findings provide evidence for further research on the potential impact of low-dose radiation on cardiovascular function. [ABSTRACT FROM AUTHOR]

To explore the radiobiological effects and related mechanisms of brain tissue after craniocerebral irradiation in young rats. Twenty-seven young male rats were randomly divided into high dose group (group C) (n=9), low dose group (group B) (n=9) and control group (group A) (n=9). The brains of rats in the group C were irradiated with 20Gy, while those in the group B were irradiated with 3Gy. The changes of body weight and organ index of rats in the three groups after craniocerebral irradiation were recorded. 1 w later, the rats were killed, the brain tissue was taken out, and the brain tissue sections were stained with hematoxylin and eosin. The migration ability was detected by cell scratch test, the levels of oxidative stress, inflammatory factors and apoptosis factors in brain tissue were observed, and the radiobiological effects and possible mechanism of brain injury were analyzed. At 3 d and 7 d after craniocerebral irradiation, the body weight of rats in the group B and group C was lower than that in the group A, and that in the group C was lower than that in the group B. Compared with the group A, the thymus and spleen organ index of the group B and the group C decreased and the decrease degree of the group C was greater than that of the group B. The normal nerve cells in the hippocampus of rats have large and round nucleoli, clear nucleoli and intact cell membrane. The pathological sections of the group B showed nerve cell injury, swelling, deformation, pale cytoplasm and tissue edema. The results of scratch test showed that the cell migration distance between the group B and the group C was larger than that in the group A at 24 h and 48 h, and the migration distance in the group C was larger than that in the group B. Compared with the group A, the serum superoxide dismutase activity decreased and the malondialdehyde content increased in the group B, while the superoxide dismutase activity and malondialdehyde content in the group C increased compared with the group B. Compared with the group A, the concentrations of tumour necrosis factor-alpha and interleukin-6 in the serum of the group B were increased, and these in the group C were higher than those of the group B. Compared with the group A, the apoptotic factors Bcl-2-associated X-protein and caspase-3 in the group B increased, while the content of B-cell lymphoma 2 decreased. Compared with the group B, the apoptotic factors Bcl-2-associated X-protein and caspase-3 increased and the content of B-cell lymphoma 2 decreased in the group C. Brain irradiation caused radiation-induced pathological damage to the brain tissue of young rats, resulting in weight loss and damage to immune organs in a dose-dependent manner. Its mechanism can be mediated by promoting inflammation, oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of different dose rates (DRs) in continuous and interrupted irradiation on in-vitro survival of the MCF-7 cell line, towards finding possible radiobiological effects of breath-hold techniques in breast radiotherapy (RT), in which intra-fractional beam interruptions and delivery prolongation can occur. Materials and Methods: MCF-7 cells were irradiated continuously or with regular interruptions using 6 MV x-rays at different accelerator DRs (50-400 cGy/min) to deliver a 2 Gy dose. The interrupted irradiation was delivered in a 10 s on, 10 s off manner. Then, cell survival and viability were studied using colony and MTT assays, respectively. Results: Survival and viability with continuous and interrupted irradiation were similar (P > 0.5). A significant increase in survival at 50, 100, and 400 cGy/min compared to 200 and 300 cGy/min was observed, also a significant decreasing and then increasing trend from 50 to 200 cGy/min and 200 to 400 cGy/min, respectively (P < 0.04). Relative to 200 cGy/min, the survival fractions at 50, 100, 300, and 400 cGy/min were 1.24, 1.23, 1.05, and 1.20 times greater, respectively. Cell viability did not show significant differences between the DRs, despite following the same trend as cell survival. Conclusion: Our results suggest that for continuous irradiation of in-vitro MCF-7 cells, with increasing DR within the 50-400 cGy/min range, sensitivity increases and then decreases (inverse effect), also that up to doubling of treatment time in breath-hold techniques does not affect in-vitro radiobiological efficacy with 200-400 cGy/min accelerator DRs. Further confirmatory studies are required. [ABSTRACT FROM AUTHOR]

While particle therapy has been used for decades for cancer treatment, there is still a lack of information on the molecular mechanisms of biomolecules radiolysis by accelerated ions. Here, we examine the effects of accelerated protons on highly concentrated native myoglobin, by means of Fourier transform infrared and UV–Visible spectroscopies. Upon irradiation, the secondary structure of the protein is drastically modified, from mostly alpha helices conformation to mostly beta elements at highest fluence. These changes are accompanied by significant production of carbon monoxide, which was shown to come from heme degradation under irradiation. The radiolytic yields of formation of denatured protein, carbon monoxide, and of heme degradation were determined, and found very close to each other: G+denatured Mb ≈ G+CO ≈ G-heme = 1.6 × 10–8 ± 0.1 × 10–8 mol/J = 0.16 ± 0.01 species/100 eV. The denaturation of the protein to a beta structure and the production of carbon monoxide under ion irradiation are phenomena that may play an important role in the biological effects of ionizing radiation. [ABSTRACT FROM AUTHOR]

Background: Cell phone and Ultra-High Frequency (UHF) waves produce oxidative stress and cause testicular toxicity. This investigation was directed to evaluate the effectiveness of Rosmarinic Acid (RA) against oxidative stress caused by UHF radiation in rats. Methods: Forty-two male Wistar rats were divided into six groups. The control received 5 mL normal saline (0.9% NaCl) by gavage, the cell phone group received 915 MHz, the UHF waves group just received 2450 MHz, the RA/cell phone group received RA plus 915 MHz, RA/UHF waves group received RA plus 2450 MHz, and RA just received RA (20 mg/kg). After 30 days of consecutive radiation, the biochemical and histopathological parameters of their testes were measured. Statistical comparison was made using one-way ANOVA followed by Tukey's post hoc test. Results: Cell phone and UHF wave radiation significantly diminished the activity of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, and glutathione content (P<0.001). On the opposite, UHF significantly increased oxidative stress indices including malondialdehyde level, nitric oxide level, and protein carbonyl content (P<0.001). UHF also significantly reduced the number of Sertoli cells, spermatogonia, primary spermatocyte, epithelial height, and seminiferous tubular and luminal diameters (P<0.001). RA, as an effective antioxidant, reverses the above-mentioned harms and moderates the adverse effects of UHF on the testes of rats by significantly diminishing the oxidative stress indices and antioxidant enzyme rise and improving the histological parameters (P<0.001). Conclusion: RA can protect the testes of rats from UHF- induced toxicity by reducing oxidative stress. RA as a food supplement might be useful for protecting humans exposed to UHF environmental contamination. [ABSTRACT FROM AUTHOR]

Objective: This research focuses on the interaction between the circadian clock and the damage caused to testicular tissue by x-ray ionizing radiation. By examining the links between circadian rhythms and radiation-induced testicular damage, a deeper understanding of the underlying mechanisms may emerge, potentially leading to new strategies to mitigate or prevent such damage and its subsequent consequences. Methods: Twenty-four Sprague-Dawley rats were divided into 3 groups. Rats in group 1 (control group) did not undergo any procedures. Rats in group 2 (day) received 6 Gy total body external x-ray radiation in a single fraction between the hours 05:00 and 06:00. Rats in group 3 (night) received 6 Gy total body external x-ray radiation in a single fraction between the hours 19:00 and 20:00. Results: The day group was compared with the control group, and a decrease in spermatogenetic cells and edematous areas was observed. In addition, there was vacuolar accumulation in the cytoplasm of spermatids in the germinal epithelium and necrotic Leydig cells in the intertubular spaces. In the night group, we observed that the changes observed in group 2 were significantly restored. In terminal deoxynucleotide transferase dUTP nick end labeling and 8-hyd roxy- 2’-de oxygu anosi ne immunohistochemical analyses, we observed significantly increased immunopositivity in group 2 compared to the control group and group 3. Conclusion: In conclusion, it reveals that the circadian clock protects against testicular damage caused by x-ray ionizing radiation. By regulating DNA repair processes, antioxidant defense mechanisms, and other important pathways, the circadian clock appears to increase the resistance of testicular tissues to radiation stress. [ABSTRACT FROM AUTHOR]

The U.S. Government is committed to maintaining a robust research program that supports a portfolio of scientific experts who are investigating the biological effects of radiation exposure. On August 17 and 18, 2023, the Radiation and Nuclear Countermeasures Program, within the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), partnered with the National Cancer Institute, NIH, the National Aeronautics and Space Administration, and the Radiation Injury Treatment Network to convene a workshop titled, Advanced Technologies in Radiation Research (ATRR), which focused on the use of advanced technologies under development or in current use to accelerate radiation research. This meeting report provides a comprehensive overview of the research presented at the workshop, which included an assembly of subject matter experts from government, industry, and academia. Topics discussed during the workshop included assessments of acute and delayed effects of radiation exposure using modalities such as clustered regularly interspaced short palindromic repeats (CRISPR) – based gene editing, tissue chips, advanced computing, artificial intelligence, and immersive imaging techniques. These approaches are being applied to develop products to diagnose and treat radiation injury to the bone marrow, skin, lung, and gastrointestinal tract, among other tissues. The overarching goal of the workshop was to provide an opportunity for the radiation research community to come together to assess the technological landscape through sharing of data, methodologies, and challenges, followed by a guided discussion with all participants. Ultimately, the organizers hope that the radiation research community will benefit from the workshop and seek solutions to scientific questions that remain unaddressed. Understanding existing research gaps and harnessing new or re-imagined tools and methods will allow for the design of studies to advance medical products along the critical path to U.S. Food and Drug Administration approval. [ABSTRACT FROM AUTHOR]

Introduction: It was a century ago, whether used separately or in combination with other medicines, that radiotherapy evolved into a successful cancer treatment. In traditional radiation therapy, a Dose Volume Histogram (DVH) is utilized for quantitative analysis of the treatment plan after the adoption of the treatment planning system. An isodose distribution is also used for qualitative analysis and evaluation of the treatment plan during this phase. The right treatment plan is assessed using physical and radiobiological models by inhouse software developed for radiation oncologists. Materials and Methods: The first process was the OSCAR (Object Scoring with Coloured Area of Regret) treatment planning system, developed by Theratronics International, Kanata, Canada in 1991, which was one of the numerous plan evaluation software programs that were established in the field of radiation medicine to analyse and regularize the dose distribution. Many plan evaluation programs have been created over the developing years, with the commercial software used primarily and the primary inclusion MATLAB, and very few have been created using Microsoft Visual Basic, C++, and Java. As a substitute for MATLAB, Python is utilized because it is freely available and has no commercial value. Results: This study's primary objective is to personalize the radiobiological effects to predict each patient by using the DVH data, which are now accessible, to improve the overall performance of the prior model. Several programming languages were initially investigated to check the portability and quick program execution to illustrate the novel ideas. It was discovered that Python was adequate for this research even if it has no economic value compared to other languages. The software receives the DVH data in text format as an input, and for convenience, it displays the output using a variety of Python widgets. Discussion: The major radiobiological parameter values, TD50/5, slope parameter (m), and volume parameter (n), are used to calculate the Tumour Control Probability (TCP) and NTCP values of numerous targets and oars from their respective DVH statistics using Python software. The evaluation of the physical indices of the treatment plans, the AAPM, RTOG, and QUANTEC protocols were used in a clinical analysis for the execution of treatment plans. Conclusion: The problem in the previous plan evaluation tool was fixed by the custom-made PYTHON program used for this research investigation, which also added clinical and radiobiological understanding of the treatment plan. The software produces a report using Microsoft Excel for the comprehensive radiobiological and dosimetric plan evaluation study for cancer patients. [ABSTRACT FROM AUTHOR]

This review discusses the relationship between cellular senescence and radiation exposure. Given the wide range of ionizing radiation sources encountered by people in professional and medical spheres, as well as the influence of natural background radiation, the question of the effect of radiation on biological processes, particularly on aging processes, remains highly relevant. The parallel relationship between natural and radiation-induced cellular senescence reveals the common aspects underlying these processes. Based on recent scientific data, the key points of the effects of ionizing radiation on cellular processes associated with aging, such as genome instability, mitochondrial dysfunction, altered expression of miRNAs, epigenetic profile, and manifestation of the senescence-associated secretory phenotype (SASP), are discussed. Unraveling the molecular mechanisms of cellular senescence can make a valuable contribution to the understanding of the molecular genetic basis of age-associated diseases in the context of environmental exposure. [ABSTRACT FROM AUTHOR]

Simple Summary: The Oriental fruit fly, Bactrocera dorsalis (Hendel), significantly impacts agriculture in Southeast Asia and some Pacific islands as a major pest. Its widespread distribution, robust invasive ability, and detrimental effects on market access categorize it as a significant threat to numerous countries. Irradiation treatment is recognized as an effective and promising approach, considered as a potential alternative to the traditional phytosanitary treatment method, methyl bromide fumigation. However, the low-oxygen environment can influence the efficacy of irradiation treatment. The aim of this study is to investigate the impact of low-oxygen levels on the phytosanitary irradiation effects against larvae of B. dorsalis. The effects of normoxic (21% O2), hypoxic (5% O2), and super-hypoxic (0.5% O2) conditions on the development and metabolic profile of third-instar larvae of B. dorsalis were evaluated and compared at phytosanitary irradiation dose. Our research emphasizes the importance of lipid metabolism pathways and their associated metabolites in the irradiation tolerance of insects; moreover, neither hypoxic nor super-hypoxic conditions have increased the emergence rate of the evaluated fruit fly species under the current phytosanitary irradiation dose. These findings provide new insights into the mechanisms of radioprotection in insects under low-oxygen environments and advocate for international organizations and regulatory agencies to update guidelines on the application of phytosanitary irradiation under hypoxic conditions. X-ray irradiation and modified atmospheres (MAs) provide eco-friendly, chemical-free methods for pest management. Although a low-oxygen atmospheric treatment improves the performance of some irradiated insects, its influence on the irradiation of quarantine insects and its impacts on pest control efficacy have yet to be investigated. Based on bioassay results, this study employed direct immersion solid-phase microextraction (DI-SPME) combined with gas chromatography-mass spectrometry (GC-MS) to determine metabolic profiles of late third-instar B. dorsalis larvae under normoxia (CON, Air), hypoxia (95% N2 + 5% O2, HY), super-hypoxia (99.5% N2 + 0.5% O2, Sup-HY), irradiation-alone (116 Gy, IR-alone), hypoxia + irradiation (HY + IR) and super-hypoxia + irradiation (Sup-HY + IR). Our findings reveal that, compared to the IR-alone group, the IR treatment under HY and Sup-HY (HY + IR and Sup-HY + IR) increases the larval pupation of B. dorsalis, and weakens the delaying effect of IR on the larval developmental stage. However, these 3 groups further hinder adult emergence under the phytosanitary IR dose of 116 Gy. Moreover, all IR-treated groups, including IR-alone, HY + IR, and Sup-HY + IR, lead to insect death as a coarctate larvae or pupae. Pathway analysis identified changed metabolic pathways across treatment groups. Specifically, changes in lipid metabolism-related pathways were observed: 3 in HY vs. CON, 2 in Sup-HY vs. CON, and 5 each in IR-alone vs. CON, HY + IR vs. CON, and Sup-HY + IR vs. CON. The treatments of IR-alone, HY + IR, and Sup-HY + IR induce comparable modifications in metabolic pathways. However, in the HY + IR, and Sup-HY + IR groups, the third-instar larvae of B. dorsalis demonstrate significantly fewer changes. Our research suggests that a low-oxygen environment (HY and Sup-HY) might enhance the radiation tolerance in B. dorsalis larvae by stabilizing lipid metabolism pathways at biologically feasible levels. Additionally, our findings indicate that the current phytosanitary IR dose contributes to the effective management of B. dorsalis, without being influenced by radioprotective effects. These results hold significant importance for understanding the biological effects of radiation on B. dorsalis and for developing IR-specific regulatory guidelines under MA environments. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is one of the most common cancers among women. Since microarray is a new method in cancer diagnosis, in the current study, the microarray library of MCF-7 breast cancer cells after irradiation was examined to predict the gene expression pattern and metabolic pathways related to it. Materials and Methods: Microarray data extracted from National Center for Biotechnology Information (NCBI) related to MCF-7 cells were analyzed by GEO2R and R software. Then the genes that had increased and decreased expression were extracted and gene ontology analysis was performed using DAVID and Enrichr databases. Results: In this study, after 48 hours of irradiation, 234 genes with Log2FC>1 increased expression and 146 genes with Log2FC<-1 decreased expression (Adjusted p value <0.05). KEGG analysis on genes with increased expression showed that these genes are related to type 1 diabetes (P=2.43E-04). The genes extracted in this pathway included HLA-DRB5, HLA-DRB4, CPE, TNF, HLA-DRB1 and HLA-DM (Adjusted p value <0.05). Also, the findings show that the genes involved in type 1 diabetes in the islets of Langerhans include CPE, MHC-II, and TNF-α. Conclusion: The findings of this study showed that the increase in irradiation time in breast cancer cells probably leads to the activation of pathways related to type 1 diabetes through CPE, MHC-II and TNF-α genes in the islets of Langerhans. [ABSTRACT FROM AUTHOR]

Objective: The effect of miR-626 on the radiosensitivity to oral squamous cell carcinoma (OSCC) was evaluated in this study. Materials and Methods: The level of miR-626 in OSCC patients was determined by analyzing the data of miRNA microarray GSE113956. miR-626 was overexpressed by miR-626 mimics and knockdown were performed by miR-626 inhibitor. The level of miR-626 was detected by quantitative real-time polymerase chain reaction. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays were used to detect the effect of miR-626 on the growth of OSCC cells. Flow cytometry was used to detect the apoptosis of OSCC cells. Western blot and dual luciferase reporter assays were used to explore the underlying mechanism of miR-626 regulating the radiosensitivity to OSCC. The effect of miR-626 on the radiosensitivity to OSCC were examined in an in vivo xenograft model. Results: The serum miR-626 level of OSCC patients was significantly higher than that of healthy controls. miR-626 mimics significantly promoted the OSCC cell growth, but the miR-626 inhibitor significantly suppressed the OSCC cell growth. Radiation combined with the miR-626 inhibitor significantly suppressed the cell proliferation and promoted the apoptosis of SCC-4 and HSC4 cells. Moreover, miR-626 regulates the nuclear factor kappa-B (NF-κB) signaling mediated by TRAF-interacting protein with forkhead-associated domain B. Furthermore, inhibition of miR-626 enhances the radiosensitivity to OSCC in nude mice. Conclusions: miR-626 inhibition enhanced the radiosensitivity to OSCC through the downregulation of NF-κB signaling. [ABSTRACT FROM AUTHOR]

For various reasons, pregnant women are occasionally exposed to ionizing radiation during radiology examinations. In these situations, it is essential to determine the radiation dose to the fetus and any associated risks. The present study attempts to calculate the mean dose for the fetus to estimate the possible cancer induction and cancer mortality risks resulting from maternal radiography exams. The GATE Monte Carlo platform and a standard voxelized pregnant phantom were employed to calculate fetal radiation dose during maternal radiography exams. The data published in Biological Effects of Ionizing Radiation VII were used to convert fetal dose to lifetime attributable risks (LARs) of cancer incidence and cancer-related mortality. The fetal doses and LARs of cancer incidence and cancer-related mortality for the radiographs of the chest and skull were negligible. The maximum LAR values for the lateral view of the abdomen in computed and digital radiography are 5598.29 and 2238.95 per 100,000 individuals, respectively. The computed radiography of the lateral view of the abdomen revealed the highest LAR of cancer-related mortality (2074.30 deaths for every 100,000 people). The radiation dose incurred by the fetus due to chest and skull radiographs was minimal and unlikely to cause any abnormalities in the fetus. The discernible elevation in the lifetime attributable risk associated with cancer incidence and mortality arising from lateral computed radiography examinations of the abdomen warrants careful consideration within the realm of maternal radiography examinations. [ABSTRACT FROM AUTHOR]

The article discusses the potential benefits of ultra-high dose rate irradiation, known as FLASH radiotherapy, in cancer treatment. FLASH-RT has been shown to reduce radiation-induced toxicity on normal tissues while maintaining similar antitumor effects as conventional radiotherapy. However, there are technological challenges in designing stable radiation sources and developing accurate dosimetric protocols for FLASH-RT. Additionally, the biological mechanisms underlying the FLASH effect are not yet fully understood. The article presents a multidisciplinary approach involving technological advancements, dosimetry, radiobiological experiments, and in silico simulations to further investigate and optimize FLASH-RT for clinical implementation. [Extracted from the article]

The text is a preface to a special issue of the Journal of Radiation Protection Dosimetry, which features selected research papers from the 23rd National Symposium on Radiation Physics (NSRP-23). The symposium was organized by the Department of Studies in Physics at the University of Mysore in collaboration with the Indian Society for Radiation Physics (ISRP). The preface highlights the importance of radiation physics in various fields and acknowledges the contributions of scientists and technologists in developing applications for ionizing radiation. It also expresses gratitude to the organizers, sponsors, authors, and reviewers involved in the symposium and publication process. [Extracted from the article]

Objective. In this paper, we present MONAS (MicrOdosimetry-based modelliNg for relative biological effectiveness (RBE) ASsessment) toolkit. MONAS is a TOPAS Monte Carlo extension, that combines simulations of microdosimetric distributions with radiobiological microdosimetry-based models for predicting cell survival curves and dose-dependent RBE. Approach. MONAS expands TOPAS microdosimetric extension, by including novel specific energy scorers to calculate the single- and multi-event specific energy microdosimetric distributions at different micrometer scales. These spectra are used as physical input to three different formulations of the microdosimetric kinetic m odel, and to the generalized stochastic microdosimetric model (GSM2), to predict dose-dependent cell survival fraction and RBE. MONAS predictions are then validated against experimental microdosimetric spectra and in vitro survival fraction data. To show the MONAS features, we present two different applications of the code: (i) the depth-RBE curve calculation from a passively scattered proton SOBP and monoenergetic 12C-ion beam by using experimentally validated spectra as physical input, and (ii) the calculation of the 3D RBE distribution on a real head and neck patient geometry treated with protons. Main results. MONAS can estimate dose-dependent RBE and cell survival curves from experimentally validated microdosimetric spectra with four clinically relevant radiobiological models. From the radiobiological characterization of a proton SOBP and 12C fields, we observe the well-known trend of increasing RBE values at the distal edge of the radiation field. The 3D RBE map calculated confirmed the trend observed in the analysis of the SOBP, with the highest RBE values found in the distal edge of the target. Significance. MONAS extension offers a comprehensive microdosimetry-based framework for assessing the biological effects of particle radiation in both research and clinical environments, pushing closer the experimental physics-based description to the biological damage assessment, contributing to bridging the gap between a microdosimetric description of the radiation field and its application in proton therapy treatment with variable RBE. [ABSTRACT FROM AUTHOR]