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Objective. To develop a computational tool that converts biological images into geometries compatible with computational software dedicated to the Monte Carlo simulation of radiation transport (TOPAS), and subsequent biological tissue responses (CompuCell3D). The depiction of individual biological entities from segmentation images is essential in computational radiobiological modeling for two reasons: image pixels or voxels representing a biological structure, like a cell, should behave as a single entity when simulating biological processes, and the action of radiation in tissues is described by the association of biological endpoints to physical quantities, as radiation dose, scored the entire group of voxels assembling a cell. Approach. The tool is capable of cropping and resizing the images and performing clustering of image voxels to create independent entities (clusters) by assigning a unique identifier to these voxels conforming to the same cluster. The clustering algorithm is based on the adjacency of voxels with image values above an intensity threshold to others already assigned to a cluster. The performance of the tool to generate geometries that reproduced original images was evaluated by the dice similarity coefficient (DSC), and by the number of individual entities in both geometries. A set of tests consisting of segmentation images of cultured neuroblastoma cells, two cell nucleus populations, and the vasculature of a mouse brain were used. Main results. The DSC was 1.0 in all images, indicating that original and generated geometries were identical, and the number of individual entities in both geometries agreed, proving the ability of the tool to cluster voxels effectively following user-defined specifications. The potential of this tool in computational radiobiological modeling, was shown by evaluating the spatial distribution of DNA double-strand-breaks after microbeam irradiation in a segmentation image of a cell culture. Significance. This tool enables the use of realistic biological geometries in computational radiobiological studies. [ABSTRACT FROM AUTHOR]

Introduction: We developed a new method that drastically speeds up radiobiological Monte Carlo radiation-track-structure (MC-RTS) calculations on a cell-by-cell basis. Methods: The technique is based on random sampling and superposition of single-particle track (SPT) standard DNA damage (SDD) files from a "pre-calculated" data library, constructed using the RTS code TOPAS-nBio, with "time stamps" manually added to incorporate dose-rate effects. This time-stamped SDD file can then be input into MEDRAS, a mechanistic kinetic model that calculates various radiation-induced biological endpoints, such as DNA double-strand breaks (DSBs), misrepairs and chromosomal aberrations, and cell death. As a benchmark validation of the approach, we calculated the predicted energy-dependent DSB yield and the ratio of direct-to-total DNA damage, both of which agreed with published in vitro experimental data. We subsequently applied the method to perform a superfast cell-by-cell simulation of an experimental in vitro system consisting of neuroendocrine tumor cells uniformly incubated with 177Lu. Results and discussion: The results for residual DSBs, both at 24 and 48 h post-irradiation, are in line with the published literature values. Our work serves as a proof-of-concept demonstration of the feasibility of a cost-effective "in silico clonogenic cell survival assay" for the computational design and development of radiopharmaceuticals and novel radiotherapy treatments more generally. [ABSTRACT FROM AUTHOR]

This article aims at presenting in a didactic way, dosimetry concepts and methods that are relevant for radio-embolization of the liver with 90Y-microspheres. The application of the medical internal radiation dose formalism to radio-embolization is introduced. This formalism enables a simplified dosimetry, where the absorbed dose in a given tissue depends on only its mass and initial activity. This is applied in the single-compartment method, partition model, for the liver, tumour and lung dosimetry, and multi-compartment method, allowing identification of multiple tumours. Voxel-based dosimetry approaches are also discussed. This allows taking into account the non-uniform uptake within a compartment, which translates into a non-uniform dose distribution, represented as a dose--volume histogram. For this purpose, dose--kernel convolution allows propagating the energy deposition around voxel-sources in a computationally efficient manner. Alternatively, local-energy deposition is preferable when the spatial resolution is comparable or larger than the beta-particle path. Statistical tools may be relevant in establishing dose--effect relationships in a given population. These include tools such as the logistic regression or receiver operator characteristic analysis. Examples are given for illustration purpose. Moreover, tumour control probability modelling can be assessed through the linear-quadratic model of Lea and Catcheside and its counterpart, the normal-tissue complication probability model of Lyman, which is suitable to the parallel structure of the liver. The selectivity of microsphere administration allows tissue sparing, which can be considered with the concept of equivalent uniform dose, for which examples are also given. The implication of microscopic deposition of microspheres is also illustrated through a liver toxicity model, even though it is not clinically validated. Finally, we propose a reflection around the concept of therapeutic index (TI), which could help tailor treatment planning by determining the treatment safety through the evaluation of TI based on treatment-specific parameters. [ABSTRACT FROM AUTHOR]

The radiobiology of tumor reirradiation is poorly understood. It pertains to tumors and their sensitivity at the time of relapse, encompassing primary tumors, metastases, or secondary cancers developed in or proximal to previously irradiated tissues. The ability to control the pathology depends, in part, on understanding this sensitivity. To date, literature data remains limited regarding changes in the radiosensitivity of tissues after initial irradiation, and most proposals are based on conjecture. The response of healthy tissues at the site of irradiation raises concerns about radio-induced complications. Cumulative dose is likely a major factor in this risk, thus using equivalent dose calculations might help reduce the risk of complications. However, the correlation between mathematical equivalence formulas and clinical effects of radiobiological origin is weak, and the lack of knowledge of the alpha/beta (α/β) ratio of healthy tissues remains an obstacle to the extensive use of these formulas. However, tissues exposed to recovery dose may have a tolerance to irradiation much higher than assumed, thus further biological work remains to be developed. Also, the functionality of previously irradiated tissues could be useful in selecting the most suitable irradiation beams. Finally, research on the genomics of irradiated healthy tissues could improve the prediction of side effects and personalize radiotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Patient-specific factors must be thoroughly analyzed to minimize the side effects of applied treatments. This study examined the radiobiological response of established and patient-derived malignant cell lines, cancer-associated fibroblasts, and skin fibroblasts to proton irradiation (IRR). Using clonogenic assay, γH2AX, and p53 staining, it was found that breast cancer cell lines of different subtypes had similar responses. However, cancer-associated fibroblasts from TNBC tumors were more resistant than those from luminal A tumors. Skin fibroblasts responded uniformly across all doses. The responses of patient-derived cell lines suggested that each patient may have a distinct radiotherapy result due to specific tumor microenvironmental characteristics. Research on different types of ionizing radiation's effects has been ongoing for years, revealing its efficacy in damaging cancer cells. Solid tumors comprise diverse cell types, each being able to respond differently to radiation. This study evaluated the radiobiological response of established (MDA-MB-231 (Triple negative breast cancer, TNBC), MCF-7 (Luminal A)) and patient-derived malignant cell lines, cancer-associated fibroblasts, and skin fibroblasts following proton IRR. All cell line types were irradiated with the proton dose of 2, 4, and 6 Gy. The radiobiological response was assessed using clonogenic assay, γH2AX, and p53 staining. It was noticeable that breast cancer lines of different molecular subtypes displayed no significant variations in their response to proton IRR. In terms of cancer-associated fibroblasts extracted from the tumor tissue, the line derived from a TNBC subtype tumor demonstrated higher resistance to ionizing radiation compared to lines isolated from luminal A tumors. Fibroblasts extracted from patients' skin responded identically to all doses of proton radiation. This study emphasizes that tumor response is not exclusively determined by the elimination of breast cancer cells, but also takes into account tumor microenvironmental variables and skin reactions. [ABSTRACT FROM AUTHOR]

Radiotherapy has played an essential role in cancer treatment for over a century, and remains one of the best-studied methods of cancer treatment. Because of its close links with the physical sciences, it has been the subject of extensive quantitative mathematical modelling, but a complete understanding of the mechanisms of radiotherapy has remained elusive. In part this is because of the complexity and range of scales involved in radiotherapy—from physical radiation interactions occurring over nanometres to evolution of patient responses over months and years. This review presents the current status and ongoing research in modelling radiotherapy responses across these scales, including basic physical mechanisms of DNA damage, the immediate biological responses this triggers, and genetic- and patient-level determinants of response. Finally, some of the major challenges in this field and potential avenues for future improvements are also discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: In this article, we report the results of an interim analysis of 81 early-stage lung cancer patients undergoing stereotactic ablative radiotherapy with the CyberKnife M6 robotic radiosurgery system, with the endpoints being treatment efficacy and tolerance. Within a median follow-up of 20 months, a grade 2/3 lung toxicity of no clinical significance was reported in 6% of the patients. A higher biological effective dose and larger irradiation lung volumes were associated with increased toxicity. The projected 24-month local progression-free survival rate was 95%. These results confirm the safety and efficacy and further cement the role of robotic stereotactic ablative radiotherapy for early-stage lung cancer patients as an eventual alternative to surgery. Background/Objectives: Surgery is the primary treatment for early-stage lung cancer. Patients with medically inoperable lung carcinomas and patients who refuse to undergo surgery are treated with definite radiotherapy. Stereotactic ablative radiotherapy (SABR) is a compelling non-invasive therapeutic modality for this group of patients that confers promising results. Methods: We report an interim analysis of an ongoing trial. Eighty-one patients with medically inoperable early-stage (T1,2N0) lung cancer underwent SABR in our institution. SABR was delivered via the CyberKnife M6 robotic radiosurgery system. The endpoints of the analysis were treatment efficacy and tolerance. Results: There were no acute or late toxicities from the skin or the connective tissue of the thorax. A grade 2/3 lung injury of non-clinical significance was noted in 6% of patients, which was directly related to a higher biologically effective dose (BEDα/β = 3) and larger irradiation lung volumes in both univariate and multivariate analyses. A local control (LC) was achieved in 100% of the patients at the first follow-up, and the projected 24-month local progression-free survival (LPFS) rate was 95%. The projected 24-month disease-specific overall survival (OS) was 94%. Conclusions: High LC and OS rates can be achieved with SABR for early-stage lung cancer, with minimal toxicity. This study continues to recruit patients. [ABSTRACT FROM AUTHOR]

Accidental exposure to high-dose radiation while pregnant has shown significant negative effects on the developing fetus. One fetal organ which has been studied is the placenta. The placenta performs all essential functions for fetal development, including nutrition, respiration, waste excretion, endocrine communication, and immunological functions. Improper placental development can lead to complications during pregnancy, as well as the occurrence of intrauterine growth-restricted (IUGR) offspring. IUGR is one of the leading indicators of fetal programming, classified as an improper uterine environment leading to the predisposition of diseases within the offspring. With numerous studies examining fetal programming, there remains a significant gap in understanding the placenta's role in irradiation-induced fetal programming. This review aims to synthesize current knowledge on how irradiation affects placental function to guide future research directions. This review provides a comprehensive overview of placental biology, including its development, structure, and function, and summarizes the placenta's role in fetal programming, with a focus on the impact of radiation on placental biology. Taken together, this review demonstrates that fetal radiation exposure causes placental degradation and immune function dysregulation. Given the placenta's crucial role in fetal development, understanding its impact on irradiation-induced IUGR is essential. [ABSTRACT FROM AUTHOR]

Purpose: Task Group 121 – Effects of ionizing radiation exposure in offspring and next generations – is a task group under the Committee 1 of the International Commission on Radiological Protection (ICRP), approved by the Main Commission on 18th November 2021. The main goals of Task Group 121 are to (1) review and update the scientific literature of relevance to radiation-related effects in the offspring of parent(s) exposed to ionizing radiation in both human and non-human biota; (2) to assess preconceptional and intrauterine effects of radiation exposure and related morbidity and mortality; and, (3) to provide advice about the level of evidence and how to consider these preconceptional and postconceptional effects in the system of radiological protection for humans and non-human biota. Methods: The Task Group is reviewing relevant literature since Publication 90 'Biological effects after prenatal irradiation (embryo and fetus)' (2003) and will include radiation-related effects on future generations in humans, animals, and plants. This review will be conducted to account for the health effects on offspring and subsequent generations in the current system of radiological protection. Radiation detriment calculation will also be reviewed. Finally, preliminary recommendations will be made to update the integration of health effects in offspring and next generations in the system of radiological protection. Results: A Workshop, jointly organized by ICRP Task Group 121 and European Radiation Protection Research Platforms MELODI and ALLIANCE was held in Budapest, Hungary, from 31st May to 2nd June 2022. Participants discussed four important topics: (1) hereditary and epigenetic effects due to exposure of the germ cell line (preconceptional exposure), (2) effects arising from exposure of the embryo and fetus (intrauterine exposure), (3) transgenerational effects on biota, and (4) its potential impact on the system of radiological protection. Conclusions: Based on the discussions and presentations during the breakout sessions, newer publications, and gaps on the current scientific literature were identified. For instance, there are some ongoing systematic reviews and radiation epidemiology reviews of intrauterine effects. There are newer methods of Monte Carlo simulation for fetal dosimetry, and advances in radiation genetics, epigenetics, and radiobiology studies. While the current impact of hereditary effects on the global detriment was reported as small, the questions surrounding the effects of radiation exposure on offspring and the next generation are crucial, recurring, and with a major focus on exposed populations. This article summarizes the workshop discussions, presentations, and conclusions of each topic and introduces the special issue of the International Journal of Radiation Biology resulting from the discussions of the meeting. [ABSTRACT FROM AUTHOR]

Irradiations at Ultra-High Dose Rate (UHDR) regimes, exceeding 40 Gy/s in single fractions lasting less than 200 ms, have shown an equivalent antitumor effect compared to conventional radiotherapy with reduced harm to normal tissues. This work details the hardware and software modifications implemented to deliver 10 MeV UHDR electron beams with a linear accelerator Elekta SL 18 MV and the beam characteristics obtained. GafChromic EBT XD films and an Advanced Markus chamber were used for dosimetry characterization, while a silicon sensor assessed the machine's beam pulses stability and repeatability. The dose per pulse, average dose rate and instantaneous dose rate in the pulse were evaluated for four experimental settings, varying the source-to-surface distance and the beam collimation, i.e., with and without the use of a cylindrical applicator. The results showed a dose per pulse from 0.6 Gy to a few tens of Gy and an average dose rate up to 300 Gy/s. The obtained results demonstrate the possibility to perform in vitro radiobiology experiments and test new technologies for beam monitoring and dosimetry at the upgraded LINAC, thus contributing to the electron UHDR research field. [ABSTRACT FROM AUTHOR]

Bioinformatics has become increasingly integral to radiation biology, also known as radiobiology, providing substantial support through data storage, conversion, visualization, and sharing. This review aims to deepen understanding of bioinformatics application in radiobiology by introducing key databases and analytical tools in radiobiology, including general bioinformatics databases, radiobiology-specific databases, data processing tools, and statistical analysis tools for differentially expressed genes (DEGs) and LC/MS analysis. This review also discusses bioinformatics applications in radiobiological fields, such as radioresistance and immune cell enrichment. Despite these advances, challenges such as data interoperability remain. Methods and projects to address these issues, such as GeCo and GMQL, are also examined.

Humans have generally evolved some adaptations to protect against UV and different levels of background ionizing radiation. Similarly, elephants and whales have evolved adaptations to protect against cancer, such as multiple copies of the tumor suppressor gene p53, due to their large size and long lifespan. The difference in cancer protection strategies between humans and elephants/whales depends on genetics, lifestyle, environmental exposures, and evolutionary pressures. In this paper, we discuss how the differences in evolutionary adaptations between humans and elephants could explain why elephants have evolved a protective mechanism against cancer, whereas humans have not. Humans living in regions with high levels of background radiation, e.g. in Ramsar, Iran where exposure rates exceed those on the surface of Mars, seem to have developed some kind of protection against the ionizing radiation. However, humans in general have not developed cancer-fighting adaptations, so they instead rely on medical technologies and interventions. The difference in cancer protection strategies between humans and elephants/whales depends on genetics, lifestyle, environmental exposures, and evolutionary pressures. In this paper, we discuss how the differences in evolutionary adaptations between humans and elephants could explain why elephants have evolved a protective mechanism against cancer, whereas humans have not. Studying elephant adaptations may provide insights into new cancer prevention and treatment strategies for humans, but further research is required to fully understand the evolutionary disparities.

Simple Summary: Radiobiology has evolved from a mechanistic model based on DNA damage, and other response factors, into a more complex model including effects on the immune system and the tumor microenvironment (TME). Irradiation has an immunomodulatory effect that can manifest as increased anti-tumor immunity or immunosuppression. Irradiation promotes anti-tumor immunity through pro-inflammatory cytokines and endothelial damage, the recruitment of immune cells, and radiation-induced immunogenic cell death (ICD), characterized by the release of damage-associated molecular patterns (DAMPs) and tumor antigens. Irradiation activates both the innate and adaptive arms of the immune system. Irradiation also produces immunosuppression via the recruitment and activation of immune cells, with immunosuppressive effects. In this work, we discuss the mechanism involved in radiation-induced immune effects on which the combination of radiotherapy and immunotherapy for gynecological cancers is based. Radiobiology has evolved from a mechanistic model based on DNA damage and response factors into a more complex model that includes effects on the immune system and the tumor microenvironment (TME). Irradiation has an immunomodulatory effect that can manifest as increased anti-tumor immunity or immunosuppression. Irradiation promotes an inflammatory microenvironment through the release of pro-inflammatory cytokines and endothelial damage, which recruit immune system cells to the irradiated area. Radiation-induced immunogenic cell death (ICD), characterized by the release of damage-associated molecular patterns (DAMPs) and tumor antigens, triggers an anti-tumor immune response of both innate and adaptive immunity. Anti-tumor immunity can manifest at a distance from the irradiated area, a phenomenon known as the abscopal effect (AE), which involves dendritic cells and CD8+ T cells. Irradiation also produces an immunosuppressive effect mediated by tumor-associated macrophages (TAMs) and regulatory T lymphocytes (Tregs), which counterbalances the immunostimulatory effect. In this work, we review the mechanisms involved in the radiation-induced immune response, which support the combined treatment of RT and immunotherapy, focusing, where possible, on gynecologic cancer. [ABSTRACT FROM AUTHOR]

The combination of high and low LET radionuclides has been tested in several patient studies to improve treatment response. Radionuclide mixtures can also be released in nuclear power plant accidents or nuclear bomb deployment. This study investigated the DNA damage response and DNA double-strand break (DSB) repair in peripheral blood mononuclear cells (PBMCs) after internal exposure of blood samples of 10 healthy volunteers to either no radiation (baseline) or different radionuclide mixtures of the α- and β-emitters [223Ra]RaCl2 and [177Lu]LuCl3, i.e., 25 mGy/75 mGy, 50 mGy/50 mGy and 75 mGy/25 mGy, respectively. DSB foci and γ-H2AX α-track enumeration directly after 1 h of exposure or after 4 h or 24 h of repair revealed that radiation-induced foci (RIF) and α-track induction in 100 cells was similar for mixed α/β and pure internal α- or β-irradiation, as were the repair rates for all radiation qualities. In contrast, the fraction of unrepaired RIF (Qβ) in PBMCs after mixed α/β-irradiation (50% 223Ra & 50% 177Lu: Qβ = 0.23 ± 0.10) was significantly elevated relative to pure β-irradiation (50 mGy: Qβ, pure = 0.06 ± 0.02), with a similar trend being noted for all mixtures. This α-dose-dependent increase in persistent foci likely relates to the formation of complex DNA damage that remains difficult to repair. [ABSTRACT FROM AUTHOR]

Background: Although the FLASH radiotherapy (FLASH) can improve the sparing of organs‐at‐risk (OAR) via the FLASH effect, it is generally a tradeoff between the physical dose coverage and the biological FLASH coverage, for which the concept of FLASH effective dose (FED) is needed to quantify the net improvement of FLASH, compared to the conventional radiotherapy (CONV). Purpose: This work will develop the first‐of‐its‐kind treatment planning method called simultaneous dose and dose rate optimization via dose modifying factor modeling (SDDRO‐DMF) for proton FLASH that directly optimizes FED. Methods: SDDRO‐DMF models and optimizes FED using FLASH dose modifying factor (DMF) models, which can be classified into two categories: (1) the phenomenological model of the FLASH effect, such as the FLASH effectiveness model (FEM); (2) the mechanistic model of the FLASH radiobiology, such as the radiolytic oxygen depletion (ROD) model. The general framework of SDDRO‐DMF will be developed, with specific DMF models using FEM and ROD, as a demonstration of general applicability of SDDRO‐DMF for proton FLASH via transmission beams (TB) or Bragg peaks (BP) with single‐field or multi‐field irradiation. The FLASH dose rate is modeled as pencil beam scanning dose rate. The solution algorithm for solving the inverse optimization problem of SDDRO‐DMF is based on iterative convex relaxation method. Results: SDDRO‐DMF is validated in comparison with IMPT and a state‐of‐the‐art method called SDDRO, with demonstrated efficacy and improvement for reducing the high dose and the high‐dose volume for OAR in terms of FED. For example, in a SBRT lung case of the dose‐limiting factor that the max dose of brachial plexus should be no more than 26 Gy, only SDDRO‐DMF met this max dose constraint; moreover, SDDRO‐DMF completely eliminated the high‐dose (V70%) volume to zero for CTV10mm (a high‐dose region as a 10 mm ring expansion of CTV). Conclusion: We have proposed a new proton FLASH optimization method called SDDRO‐DMF that directly optimizes FED using phenomenological or mechanistic models of DMF, and have demonstrated the efficacy of SDDO‐DMF in reducing the high‐dose volume or/and the high‐dose value for OAR, compared to IMPT and a state‐of‐the‐art method SDDRO. [ABSTRACT FROM AUTHOR]

The effects of low-dose radiation exposure remain a controversial topic in radiation biology. This study compares early (0.5, 4, 24, 48, and 72 h) and late (5, 10, and 15 cell passages) post-irradiation changes in γH2AX, 53BP1, pATM, and p-p53 (Ser-15) foci, proliferation, autophagy, and senescence in primary fibroblasts exposed to 100 and 2000 mGy X-ray radiation. The results show that exposure to 100 mGy significantly increased γH2AX, 53BP1, and pATM foci only at 0.5 and 4 h post irradiation. There were no changes in p-p53 (Ser-15) foci, proliferation, autophagy, or senescence up to 15 passages post irradiation at the low dose. [ABSTRACT FROM AUTHOR]

Several scientific themes are reviewed in the context of the 75-year period relevant to this special platinum issue of Radiation Research. Two criteria have been considered in selecting the scientific themes. One is the exposure of the associated research activity in the annual meetings of the Radiation Research Society (RRS) and in the publications of the Society's Journal, thus reflecting the interest of members of RRS. The second criteria is a focus on contributions from Australian members of RRS. The first theme is the contribution of radiobiology to radiation oncology, featuring two prominent Australian radiation oncologists, the late Rod Withers and his younger colleague, Lester Peters. Two other themes are also linked to radiation oncology; preclinical research aimed at developing experimental radiotherapy modalities, namely microbeam radiotherapy (MRT) and Auger endoradiotherapy. The latter has a long history, in contrast to MRT, especially in Australia, given that the associated medical beamline at the Australian Synchrotron in Melbourne only opened in 2011. Another theme is DNA repair, which has a trajectory parallel to the 75-year period of interest, given the birth of molecular biology in the 1950s. The low-dose radiobiology theme has a similar timeline, predominantly prompted by the nuclear era, which is also connected to the radioprotector theme, although radioprotectors also have a long-established potential utility in cancer radiotherapy. Finally, two themes are associated with biodosimetry. One is the micronucleus assay, highlighting the pioneering contribution from Michael Fenech in Adelaide, South Australia, and the other is the γ-H2AX assay and its widespread clinical applications. [ABSTRACT FROM AUTHOR]

The aim of this paper is to review the history surrounding the discovery of lethal mutations, later described as delayed reproductive death. Lethal mutations were suggested very early on, to be due to a generalised instability in a cell population and are considered now to be one of the first demonstrations of "radiation-induced genomic instability" which led later to the establishment of the field of "non-targeted effects." The phenomenon was first described by Seymour et al. in 1986 and was confirmed by Trott's group in Europe and by Little and colleagues in the United States before being extended by Mendonca et al. in 1989, who showed conclusively that the distinguishing feature of lethal mutation occurrence was that it happened suddenly after about 9–10 population doublings in progeny which had survived the original dose of ionizing radiation. However, many authors then suggested that in fact, lethal mutations were implicit in the original experiments by Puck and Marcus in 1956 and were described in the extensive work by Sinclair in 1964, who followed clonal progeny for up to a year after irradiation and described "small colony formation" as a persistent consequence of ionizing radiation exposure. In this paper, we examine the history from 1956 to the present using the period from 1986–1989 as an anchor point to reach into the past and to go forward through the evolution of the field of low dose radiobiology where non-targeted effects predominate. [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]

Numerous dose rate effects have been described over the past 6–7 decades in the radiation biology and radiation oncology literature depending on the dose rate range being discussed. This review focuses on the impact and understanding of altering dose rates in the context of radiation therapy, but does not discuss dose rate effects as relevant to radiation protection. The review starts with a short historic review of early studies on dose rate effects, considers mechanisms thought to underlie dose rate dependencies, then discusses some current issues in clinical findings with altered dose rates, the importance of dose rate in brachytherapy, and the current timely topic of the use of very high dose rates, so-called FLASH radiotherapy. The discussion includes dose rate effects in vitro in cultured cells, in in vivo experimental systems and in the clinic, including both tumors and normal tissues. Gaps in understanding dose rate effects are identified, as are opportunities for improving clinical use of dose rate modulation. [ABSTRACT FROM AUTHOR]

Reliable dosimetry systems are crucial for radiobiological experiments either to quantify the biological consequences of ionizing radiation or to reproduce results by other laboratories. Also, they are essential for didactic purposes in the field of radiation research. Professional dosemeters are expensive and difficult to use in exposure facilities with closed exposure chambers. Consequently, a simple, inexpensive, battery-driven dosemeter was developed that can be easily built using readily available components. Measurements were performed to validate its readout with photons of different energy and dose rate and to demonstrate the applicability of the dosemeter. It turned out that the accuracy of the dose measurements using the developed dosemeter was better than 10%, which is satisfactory for radiobiological experiments. It is concluded that this dosemeter can be used both for determining the dose rates of an exposure facility and for educational purposes. [ABSTRACT FROM AUTHOR]

With the widespread application of nuclear technology across various fields, ionizing radiation-induced injuries are becoming increasingly common. The bone marrow (BM) hematopoietic tissue is a primary target organ of radiation injury. Recent researches have confirmed that ionizing radiation-induced hematopoietic dysfunction mainly results from BM hematopoietic stem cells (HSCs) injury. Additionally, disrupting and reshaping BM microenvironment is a critical factor impacting both the injury and regeneration of HSCs post radiation. However, the regulatory mechanisms of ionizing radiation injury to BM HSCs and their microenvironment remain poorly understood, and prevention and treatment of radiation injury remain the focus and difficulty in radiation medicine research. In this review, we aim to summarize the effects and mechanisms of ionizing radiation-induced injury to BM HSCs and microenvironment, thereby enhancing our understanding of ionizing radiation-induced hematopoietic injury and providing insights for its prevention and treatment in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Peptide receptor radionuclide therapy (PRRT) is a potential new treatment option for patients with meningiomas, the most common form of adult intracranial brain tumors. During PRRT, targeted radiation is delivered to the tumor through a radiolabeled peptide binding a receptor commonly overexpressed in meningioma cells. Unfortunately, preclinical research into therapy effects is limited due to the lack of appropriate in vitro models. Here, we aimed to develop an easy-to-use, scaffold-free patient-derived 3D culture model to support this research. Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTA-TATE has recently been evaluated for the treatment of meningioma patients. However, current knowledge of the underlying radiation biology is limited, in part due to the lack of appropriate in vitro models. Here, we demonstrate proof-of-concept of a meningioma patient-derived 3D culture model to assess the short-term response to radiation therapies such as PRRT and external beam radiotherapy (EBRT). We established short-term cultures (1 week) for 16 meningiomas with high efficiency and yield. In general, meningioma spheroids retained characteristics of the parental tumor during the initial days of culturing. For a subset of tumors, clear changes towards a more aggressive phenotype were visible over time, indicating that the culture method induced dedifferentiation of meningioma cells. To assess PRRT efficacy, we demonstrated specific uptake of 177Lu-DOTA-TATE via somatostatin receptor subtype 2 (SSTR2), which was highly overexpressed in the majority of tumor samples. PRRT induced DNA damage which was detectable for an extended timeframe as compared to EBRT. Interestingly, levels of DNA damage in spheroids after PRRT correlated with SSTR2-expression levels of parental tumors. Our patient-derived meningioma culture model can be used to assess the short-term response to PRRT and EBRT in radiobiological studies. Further improvement of this model should pave the way towards the development of a relevant culture model for assessment of the long-term response to radiation and, potentially, individual patient responses to PRRT and EBRT. [ABSTRACT FROM AUTHOR]

Objective: This study aims to assess the current research status, focus areas, and developmental trends in nasopharyngeal carcinoma (NPC) through a bibliometric analysis. Methods: Articles focusing on NPC published from 2000 to 2023 were retrieved from the Web of Science database. VOSviewer and CiteSpace were used for bibliometric and visual analysis. Results: A total of 14516 related publications were retrieved. There has been a steady increase in the number of NPC-related publications from 2000 to 2023. China was the dominant country in this field with 8948 papers (61.64%), followed by the USA (2234, 15.39%). Sun Yat-sen University was the most influential institution, while Ma J was the most prolific author. Furthermore, Head And Neck-journal For The Sciences And Specialties Of The Head And Neck was the most prolific journal. International Journal of Radiation Oncology Biology Physics had the highest total citation counts. "Introduction chemotherapy", "Concurrent chemotherapy", "Epithelial-mesenchymal transition", "Cancer stem cells", "MicroRNAs", "LncRNA", "Exosomes", and "Biomarker" were the most common keywords. The reference "Chen YP, 2019, Lancet" had the highest citations and strong outbreak value. Conclusion: The past two decades have witnessed a significant increase in research on NPC. The optimization of treatment mode is the most widely studied aspect at present. The mechanism of occurrence and development and the most favorable diagnostic and therapeutic targets are the research hotspots in the future. [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]

Esophageal cancer (EC) is a malignant tumour with high morbidity and mortality rates. Recent studies have shown that much progress has been made in the research of radiotherapy in EC. This study aims to provide a comprehensive overview of the knowledge structure and research hotspots of radiotherapy in EC through bibliometrics. Publications related to radiotherapy in EC from 2014 to 2023 were searched on the web of science core collection database. VOSviewers, CiteSpace and R package 'bibliometrix' were used to conduct this bibliometric analysis. In total, 4258 articles from 76 countries led by China and the USA were included. The Chinese Academy of Medical Sciences—Peking Union Medical College has the highest number of publications. International Journal of Radiation Oncology Biology Physics is the most popular journal and also the most co-cited journal in this field. These publications come from 21 972 authors among which Liao Zhongxing had published the most papers and Cooper JS was co-cited most often. Neoadjuvant chemoradiotherapy and strategies based on it are the main topics in this research field. 'IMRT' and 'immunotherapy' are the primary keywords of emerging research hotspots. This is a bibliometric study that comprehensively summarizes the research trends and developments of radiotherapy in EC. This information identifies recent research frontiers and hot directions, which will provide a reference for scholars studying radiotherapy in EC. [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]

Background: Radiation therapy (RT) is a key anti-cancer treatment that involves using ionizing radiation to kill tumor cells. However, this therapy can lead to short- and long-term adverse effects due to radiation exposure of surrounding normal tissue. The type of DNA damage inflicted by radiation therapy determines its effectiveness. High levels of genotoxic damage can lead to cell cycle arrest, senescence, and cell death, but many tumors can cope with this damage by activating protective mechanisms. Intrinsic and acquired radioresistance are major causes of tumor recurrence, and understanding these mechanisms is crucial for cancer therapy. The mechanisms behind radioresistance involve processes like hypoxia response, cell proliferation, DNA repair, apoptosis inhibition, and autophagy. Conclusion: Here we briefly review the role of genetic and epigenetic factors involved in the modulation of DNA repair and DNA damage response that promote radioresistance. In addition, leveraging our recent results on the effects of low dose rate (LDR) of ionizing radiation on Drosophila melanogaster we discuss how this model organism can be instrumental in the identification of conserved factors involved in the tumor resistance to RT. [ABSTRACT FROM AUTHOR]

At its very core, radiation oncology involves a trade-off between the benefits and risks of exposing tumors and normal tissue to relatively high doses of ionizing radiation. This trade-off is particularly critical in childhood cancer survivors (CCS), in whom both benefits and risks can be hugely consequential due to the long life expectancy if the primary cancer is controlled. Estimating the normal tissue–related risks of a specific radiation therapy plan in an individual patient relies on predictive mathematical modeling of empirical data on adverse events. The Pediatric Normal-Tissue Effects in the Clinic (PENTEC) collaborative network was formed to summarize and, when possible, to synthesize dose-volume-response relationships for a range of adverse events incident in CCS based on the literature. Normal-tissue clinical radiation biology in children is particularly challenging for many reasons: (1) Childhood malignancies are relatively uncommon—constituting approximately 1% of new incident cancers in the United States—and biologically heterogeneous, leading to many small series in the literature and large variability within and between series. This creates challenges in synthesizing data across series. (2) CCS are at an elevated risk for a range of adverse health events that are not specific to radiation therapy. Thus, excess relative or absolute risk compared with a reference population becomes the appropriate metric. (3) Various study designs and quantities to express risk are found in the literature, and these are summarized. (4) Adverse effects in CCS often occur 30, 50, or more years after therapy. This limits the information content of series with even very extended follow-up, and lifetime risk estimates are typically extrapolations that become dependent on the mathematical model used. (5) The long latent period means that retrospective dosimetry is required, as individual computed tomography–based radiation therapy plans gradually became available after 1980. (6) Many individual patient-level factors affect outcomes, including age at exposure, attained age, lifestyle exposures, health behaviors, other treatment modalities, dose, fractionation, and dose distribution. (7) Prospective databases with individual patient-level data and radiation dosimetry are being built and will facilitate advances in dose-volume-response modeling. We discuss these challenges and attempts to overcome them in the setting of PENTEC. [ABSTRACT FROM AUTHOR]

Advancements in molecular imaging and drug targeting have created a renaissance in the development of radiopharmaceuticals for therapy and theranostics. While some radiopharmaceuticals, such as Na[131I]I, have been used clinically for decades, new agents are being approved using small‐molecules, peptides, and antibodies for targeting. As these agents are being developed, the need to understand dosimetry and biologic effects of the systemically delivered radiotherapy becomes more important, particularly as highly potent radiopharmaceuticals using targeted alpha therapy become clinically utilized. As the processes being targeted become more complex, and the radiobiology of different particulate radiation becomes more diverse, models that better recapitulate human cancer and geometry are necessary. Companion animals develop many of the same types of cancer, carrying many of the same genetic drivers as those seen in people, and the scale and geometry of tumours in dogs more closely mimics those in humans than murine tumour models. Key translational challenges in oncology, such as alterations in tumour microenvironment, hypoxia, heterogeneity, and geometry are addressed by companion animal models. This review paper will provide background on radiopharmaceutical targeting techniques, review the use of radiopharmaceuticals in companion animal oncology, and explore the translational value of treating these patients in terms of dosimetry, treatment outcomes, and normal tissue complication rates. [ABSTRACT FROM AUTHOR]

Simple Summary: Our understanding of the underlying biology of proton therapy in head and neck cancers is limited. Here, we assessed the proton therapy-related radiobiological processes in head and neck cancer cells. We showed that proton therapy resulted in biological effects similar to those of classical photon-based radiotherapy. Photon-based radiotherapy (XRT) is one of the most frequently used treatment modalities for HPV-negative and HPV-positive locally advanced head and neck squamous cell carcinoma (HNSCC). However, locoregional recurrences and normal RT-associated toxicity remain major problems for these patients. Proton therapy (PT), with its dosimetric advantages, can present a solution to the normal toxicity problem. However, issues concerning physical delivery and the lack of insights into the underlying biology of PT hamper the full exploitation of PT. Here, we assessed the radiobiological processes involved in PT in HPV-negative and HPV-positive HNSCC cells. We show that PT and XRT activate the DNA damage-repair and stress response in both HPV-negative and HPV-positive cells to a similar extent. The activation of these major radiobiological mechanisms resulted in equal levels of clonogenic survival and mitotic cell death. Altogether, PT resulted in similar biological effectiveness when compared to XRT. These results emphasize the importance of dosimetric parameters when exploiting the potential of increased clinical effectiveness and reduced normal tissue toxicity in PT treatment. [ABSTRACT FROM AUTHOR]

The primary emphasis of photoimmunology is the impact of nonionizing radiation on the immune system. With the development of terahertz (THz) and sub-terahertz (sub-THz) technology, the biological effects of this emerging nonionizing radiation, particularly its influence on immune function, remain insufficiently explored but are progressively attracting attention. Here, we demonstrated that 0.1 sub-THz radiation can modulate the immune system and alleviate symptoms of arthritis in collagen-induced arthritis (CIA) mice through a nonthermal manner. The application of 0.1 sub-THz irradiation led to a decrease in proinflammatory factors within the joints and serum, reducing the levels of blood immune cells and the quantity of splenic CD4+ T cells. Notably, 0.1 sub-THz irradiation restored depleted Treg cells in CIA mice and re-established the Th17/Treg equilibrium. These findings suggested that sub-THz irradiation plays a crucial role in systemic immunoregulation. Further exploration of its immune modulation mechanisms revealed the anti-inflammatory properties of 0.1 sub-THz on LPS-stimulated skin keratinocytes. Through the reduction in NF-κB signaling and NLRP3 inflammasome activation, 0.1 sub-THz irradiation effectively decreased the production of inflammatory factors and immune-active substances, including IL-1β and PGE2, in HaCaT cells. Consequently, 0.1 sub-THz irradiation mitigated the inflammatory response and contributed to the maintenance of immune tolerance in CIA mice. This research provided significant new evidence supporting the systemic impacts of 0.1 sub-THz radiation, particularly on the immune system. It also enhanced the field of photoimmunology and offered valuable insights into the potential biomedical applications of 0.1 sub-THz radiation for treating autoimmune diseases. [ABSTRACT FROM AUTHOR]

One among several advantages of measure transport methods is that they allow or a unified framework for processing and analysis of data distributed according to a wide class of probability measures. Within this context, we present results from computational studies aimed at assessing the potential of measure transport techniques, specifically, the use of triangular transport maps, as part of a workflow intended to support research in the biological sciences. Scenarios characterized by the availability of limited amount of sample data, which are common in domains such as radiation biology, are of particular interest. We find that when estimating a distribution density function given limited amount of sample data, adaptive transport maps are advantageous. In particular, statistics gathered from computing series of adaptive transport maps, trained on a series of randomly chosen subsets of the set of available data samples, leads to uncovering information hidden in the data. As a result, in the radiation biology application considered here, this approach provides a tool for generating hypotheses about gene relationships and their dynamics under radiation exposure. [ABSTRACT FROM AUTHOR]

BackgroundNormal tissue sparing from radiation damage upon ultra-high dose rate irradiation, known as the FLASH effect with an equivalent tumor response, has been widely reported in murine skin models, and translation of this type of radiotherapy to humans has already begun, with skin sparing being a primary outcome expected.MethodsThis study reviews the status of the field, focusing on the proposed mechanisms and skin response assays, outlining what has become known in terms of input parameters that might control the magnitude of the FLASH effect.ResultsMurine studies have largely focused on acute damage responses, developing over 3–8 weeks, to single doses of FLASH versus conventional dose rate (CDR), suggesting that at dose rates above tens of Gray per second, with a total dose of more than 20 Gy, the FLASH effect is induced. Fractionated delivery appears to be possible, although fraction sizes >17 Gy appear to be needed for sparing efficacy. The interplay between the dose rate and total dose per fraction remains to be fully elucidated. Oxygen is a modulator of efficacy, with both hypoxia and hyperoxia diminishing the effect of FLASH. Measurement of transient changes in oxygen levels is possible and may be a marker of treatment efficacy.ConclusionTaken together, murine skin data provide important information for translational studies, despite the associated limitations. Studies of later-term sparing effects, as well as studies on pig skin, are needed to take the next step in assessing translational FLASH efficacy. The control of biological factors, such as tissue oxygenation, may be required to understand and control the response.

Despite the expected direct effects of radiation on DNA through its direct interaction with the biomolecule, research indicates that radiation also interacts with the DNA’s environment, resulting in indirect effects. Therefore, in this study, we explored the feasibility of using the quartz tuning fork (QTF) sensor system in biomedical applications, specifically in detecting DNA damage caused by low doses of gamma radiation, directly and indirectly. We differentiated between direct and indirect damage by analyzing the fork’s resonance frequency changes. This experiment was divided into three stages: before, during, and after irradiation. Each stage involved samples of pure DNA and DNA in a 60-µL aqueous solution, evaluated under identical conditions. Before irradiation, we measured frequency shifts (Δf) over a 20-min period, resulting in values of 19.34, 20.25, and 7.6 Hz for water, DNA, and DNA in water, respectively. Subsequently, the samples were irradiated with cesium-137 for the specified duration, resulting in frequency shifts of ∼ 39.21, 28.37, and 41.23 Hz for the same conditions. Our investigations showed an increase in Δf from 20.25 to 28.3 Hz at doses ranging from 7.5 to 30 µGy for pure DNA. Interestingly, DNA in aqueous solution exhibited hypersensitivity to radiation, with frequency shifts ranging from 7.6 to 41.23 Hz. Furthermore, we observed a significant difference in frequency shift after irradiation between pure DNA and DNA in water, with shifts of ∼ 70.75–98.45 Hz and 56.32–79.28 Hz for DNA and DNA in water, respectively. This result indicates a significant increase in DNA damage in aqueous environments, driven by the generation of active hydroxyl radicals (OH−), resulting in base damage and an associated increase in strand breaks. Consequently, our research indicates a lack of substantial direct impact on DNA repair owing to the absence of a conducive postirradiation environment. Therefore, QTF is a valuable biomarker for radiation sensitivity and is promising for future applications as a mass-sensitive biosensor.

The article discusses the effects of ionizing radiation exposure on offspring and future generations. It highlights the concerns surrounding the potential harmful effects of radiation on prenatal development and reproductive health. The article references numerous studies and reports that have investigated the risks and consequences of radiation exposure, particularly during critical periods of pregnancy. It emphasizes the need for more research and data to better understand the complexities involved and calls for long-term epidemiological studies and advancements in genetic and molecular techniques. [Extracted from the article]

The physiological process of iodine uptake in the thyroid is used for 131I treatment of thyroid diseases. Children are more sensitive to radiation compared to adults and may react differently to 131I exposure. The aims of this study were to evaluate the effects on thyroid protein expression in young and adult rats one year after 131I injection and identify potential biomarkers related to 131I exposure, absorbed dose, and age. Twelve Sprague Dawley rats (young and adults) were i.v. injected with 50 kBq or 500 kBq 131I and killed twelve months later. Twelve untreated rats were used as age-matched controls. Quantitative proteomics, statistical analysis, and evaluation of biological effects were performed. The effects of irradiation were most prominent in young rats. Protein biomarker candidates were proposed related to age, absorbed dose, thyroid function, and cancer, and a panel was proposed for 131I exposure. In conclusion, the proteome of rat thyroid was differentially regulated twelve months after low-intermediate dose exposure to 131I in both young and adult rats. Several biomarker candidates are proposed for 131I exposure, age, and many of them are known to be related to thyroid function or thyroid cancer. Further research on human samples is needed for validation. Data are avaiable via ProteomeXchange with identifier PXD024786.

Abstract Background Glioblastoma is an extremely aggressive malignant tumor with a very poor prognosis. Due to the increased proliferation rate of glioblastoma, there is the development of hypoxic regions, characterized by an increased concentration of copper (Cu). Considering this, 64Cu has attracted attention as a possible theranostic radionuclide for glioblastoma. In particular, [64Cu]CuCl2 accumulates in glioblastoma, being considered a suitable agent for positron emission tomography. Here, we explore further the theranostic potential of [64Cu]CuCl2, by studying its therapeutic effects in advanced three-dimensional glioblastoma cellular models. First, we established spheroids from three glioblastoma (T98G, U373, and U87) and a non-tumoral astrocytic cell line. Then, we evaluated the therapeutic responses of spheroids to [64Cu]CuCl2 exposure by analyzing spheroids' growth, viability, and cells' proliferative capacity. Afterward, we studied possible mechanisms responsible for the therapeutic outcomes, including the uptake of 64Cu, the expression levels of a copper transporter (CTR1), the presence of a cancer stem cell population, and the production of reactive oxygen species (ROS). Results Results revealed that [64Cu]CuCl2 is able to significantly reduce spheroids' growth and viability, while also affecting cells' proliferation capacity. The uptake of 64Cu, the presence of cancer stem-like cells and the production of ROS were in accordance with the therapeutic response. However, expression levels of CTR1 were not in agreement with uptake levels, revealing that other mechanisms could be involved in the uptake of 64Cu. Conclusions Overall, our results further support [64Cu]CuCl2 potential as a theranostic agent for glioblastoma, unveiling potential mechanisms that could be involved in the therapeutic response.

For missions beyond low Earth orbit to the moon or Mars, space explorers will encounter a complex radiation field composed of various ion species with a broad range of energies. Such missions pose significant radiation protection challenges that need to be solved in order to minimize exposures and associated health risks. An innovative galactic cosmic ray simulator (GCRsim) was recently developed at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL). The GCRsim technology is intended to represent major components of the space radiation environment in a ground analog laboratory setting where it can be used to improve understanding of biological risks and serve as a testbed for countermeasure development and validation. The current GCRsim consists of 33 energetic ion beams that collectively simulate the primary and secondary GCR field encountered by humans in space over the broad range of particle types, energies, and linear energy transfer (LET) of interest to health effects. A virtual workshop was held in December 2020 to assess the status of the NASA baseline GCRsim. Workshop attendees examined various aspects of simulator design, with a particular emphasis on beam selection strategies. Experimental results, modeling approaches, areas of consensus, and questions of concern were also discussed in detail. This report includes a summary of the GCRsim workshop and a description of the current status of the GCRsim. This information is important for future advancements and applications in space radiobiology.

In recent decades, the principal goals of participants in the field of radiation biologists have included defining dose thresholds for cancer and non-cancer endpoints to be used by regulators, clinicians and industry, as well as informing on best practice radiation utilization and protection applications. Importantly, much of this work has required an intimate relationship between "bench" radiation biology scientists and their target audiences (such as physicists, medical practitioners and epidemiologists) in order to ensure that the requisite gaps in knowledge are adequately addressed. However, despite the growing risk for public exposure to higher-than-background levels of radiation, e.g. from long-distance travel, the increasing use of ionizing radiation during medical procedures, the threat from geopolitical instability, and so forth, there has been a dramatic decline in the number of qualified radiation biologists in the U.S. Contributing factors are thought to include the loss of applicable training programs, loss of jobs, and declining opportunities for advancement. This report was undertaken in order to begin addressing this situation since inaction may threaten the viability of radiation biology as a scientific discipline.

This work reports on a model that describes patient-specific absorbed dose-dependent DNA damage response in peripheral blood mononuclear cells of thyroid cancer patients during radioiodine therapy and compares the results with the ex vivo DNA damage response in these patients. Blood samples of 18 patients (nine time points up to 168 h post-administration) were analyzed for radiation-induced γ-H2AX + 53BP1 DNA double-strand break foci (RIF). A linear one-compartment model described the absorbed dose-dependent time course of RIF (Parameters: c characterizes DSB damage induction; k1 and k2 are rate constants describing fast and slow repair). The rate constants were compared to ex vivo repair rates. A total of 14 patient datasets could be analyzed; c ranged from 0.012 to 0.109 mGy−1, k2 from 0 to 0.04 h−1. On average, 96% of the damage is repaired quickly with k1 (range: 0.19–3.03 h−1). Two patient subgroups were distinguished by k1-values (n = 6, k1 > 1.1 h−1; n = 8, k1 < 0.6 h−1). A weak correlation with patient age was observed. While induction of RIF was similar among ex vivo and in vivo, the respective repair rates failed to correlate. The lack of correlation between in vivo and ex vivo repair rates and the applicability of the model to other therapies will be addressed in further studies. [ABSTRACT FROM AUTHOR]

The Canfranc Underground Laboratory in Spain has established a Biology Platform to study the effects of low background radiation on living organisms. The platform consists of two laboratories, one underground and one on the surface, which replicate biology experiments under different cosmic radiation backgrounds. The access protocol includes open calls for experimental proposals, and eight experiments have already been approved and are underway. The platform aims to explore extremophiles, viral infection, immune system, multicellularity, development, aging, and the response of life to microgravity in the absence of radiation. The use of underground laboratories, known as Deep Underground Laboratories (DULs), provides a unique setting to study the effects of reduced radiation on various organisms. Several experiments have been conducted, focusing on parameters such as bacterial growth and viability, mutation rate, aging, and cellular response to DNA damage. The results obtained so far have shown differences in count rates, development, and infection progress compared to experiments conducted on the surface. The use of DULs not only advances our understanding of the effects of radiation on life but also has implications for space exploration and the study of life in extreme environments. The document provides additional information about the author contributions, funding, conflict of interest, and references to other related studies and research projects. [Extracted from the article]

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]

Based on the need for radiobiological databases, in this work, we mined experimental ionizing radiation data of human cells treated with X-rays, γ-rays, carbon ions, protons and α-particles, by manually searching the relevant literature in PubMed from 1980 until 2024. In order to calculate normal and tumor cell survival α and β coefficients of the linear quadratic (LQ) established model, as well as the initial values of the double-strand breaks (DSBs) in DNA, we used WebPlotDigitizer and Python programming language. We also produced complex DNA damage results through the fast Monte Carlo code MCDS in order to complete any missing data. The calculated α/β values are in good agreement with those valued reported in the literature, where α shows a relatively good association with linear energy transfer (LET), but not β. In general, a positive correlation between DSBs and LET was observed as far as the experimental values are concerned. Furthermore, we developed a biophysical prediction model by using machine learning, which showed a good performance for α, while it underscored LET as the most important feature for its prediction. In this study, we designed and developed the novel radiobiological 'RadPhysBio' database for the prediction of irradiated cell survival (α and β coefficients of the LQ model). The incorporation of machine learning and repair models increases the applicability of our results and the spectrum of potential users. [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]

Humans have generally evolved some adaptations to protect against UV and different levels of background ionizing radiation. Similarly, elephants and whales have evolved adaptations to protect against cancer, such as multiple copies of the tumor suppressor gene p53, due to their large size and long lifespan. The difference in cancer protection strategies between humans and elephants/whales depends on genetics, lifestyle, environmental exposures, and evolutionary pressures. In this paper, we discuss how the differences in evolutionary adaptations between humans and elephants could explain why elephants have evolved a protective mechanism against cancer, whereas humans have not. Humans living in regions with high levels of background radiation, e.g. in Ramsar, Iran where exposure rates exceed those on the surface of Mars, seem to have developed some kind of protection against the ionizing radiation. However, humans in general have not developed cancer-fighting adaptations, so they instead rely on medical technologies and interventions. The difference in cancer protection strategies between humans and elephants/whales depends on genetics, lifestyle, environmental exposures, and evolutionary pressures. In this paper, we discuss how the differences in evolutionary adaptations between humans and elephants could explain why elephants have evolved a protective mechanism against cancer, whereas humans have not. Studying elephant adaptations may provide insights into new cancer prevention and treatment strategies for humans, but further research is required to fully understand the evolutionary disparities. [ABSTRACT FROM AUTHOR]