Purpose Radiation-induced skin injury is a common complication that seriously affects the follow-up treatment and life quality of tumor patients. Nocardia rubra cell‐wall skeleton (N-CWS) has been reported to have pro-angiogenesis effects, and its role on RISI remains unclear. The aim of this study was to investigate its effect on repair of radiation induced skin injury. Materials and Methods After exposure to 45 Gy X-rays, the irradiated areas of SD rats were treated by N-CWS every 3 days. The radioprotective effects of N-CWS were evaluated by body weight changes, skin scores, H&E staining and TUNEL staining. Microvascular monitoring system and immunofluorescence staining of CD31 were performed to assess angiogenic capacity in vivo. In vitro, the activity and apoptosis of HUVECs were measured by CCK8 and flow cytometry. The angiogenic capacity of HUVECs was evaluated by tubule formation assay and Transwell assay. Western blot was performed to verify the possible mechanisms of the protective effect of N-CWS against radiation-induced skin damage. Results N-CWS was demonstrated to have low toxicity and radioprotective effects, maintained cell activity and attenuated radiation-induced apoptosis. In addition, N-CWS attenuated radiation-induced vascular injury in vivo and in vitro. Furthermore, P38 MAPK was shown to be associated with the radiation protection capability of N-CWS in HUVECs. Conclusions N-CWS promoted the repair of radiation-induced skin injury by enhancing angiogenesis, and the mechanism was related to the activation of P38 MAPK.

Purpose The transgenerational effects of preconception parental radiation exposure in humans remain unclear. We assessed genomic integrity in adult children of British nuclear test (NT) veterans—a community that has expressed long-standing concerns about adverse health effects, including in their offspring—to investigate for any constitutional chromosomal abnormalities and/or cytogenetic indicators of genomic instability that might be associated with paternal participation at NT sites. Materials and Methods Peripheral blood samples were obtained from 86 adult children (45 from nuclear test (NT) and 41 control), all born to veterans from the British Army, Royal Air Force, or Royal Navy. Results G-banded karyotyping revealed no constitutional chromosomal abnormalities in any NT sample, including those from families reporting adverse health outcomes. We next assessed for unstable aberrations using conventional Giemsa staining and found some evidence of instability. Specifically, a small subset of NT children (N = 4) showed elevated chromatid aberration frequencies (7.81 ± 4.01 per 100 cells) compared with controls (4.36 ± 0.62; N = 26). To investigate further, we analyzed matched veteran father–child pairs observing a weak association between fathers’ unstable aberration burden and chromatid aberrations in their children, suggesting a potential transgenerational effect. This positive trend was most pronounced in the small group of families (N = 8; 2 control and 6 NT) previously identified as being enriched for mutation signature SBS16 in the germline. Conclusions Although based on a small sample size, this observation warrants further investigation to understand the significance of SBS16, if any, including whether it may serve as a potential transgenerational mutational signature of radiation exposure. Overall, and in the context of health concerns raised by NT families, none of the self-reported health-related variables showed any association with unstable aberration burden in either the veteran fathers or their adult children.

Introduction The vertebrate retina is a laminated tissue with a relatively simple structure compared with the brain, and its accessibility makes it an excellent model for studying damage and repair in the central nervous system. This study investigated the regenerative process of the photoreceptor layer in medaka (Oryzias latipes) larvae following embryonic exposure to sub-lethal gamma irradiation and examined whether transient damage influences visual function using the optomotor response (OMR) assay. Methods Medaka embryos at 3 days post fertilization (dpf) were irradiated with 7–10 Gy to determine the lethal threshold, from which 8 Gy was determined to be a sub-lethal dose. In 8 Gy–irradiated embryos, eye size was assessed by stereomicroscopy and photoreceptor regeneration was histologically evaluated by Zpr1 immunohistochemistry at 8, 14, and 21 dpf. Visual function was evaluated by optomotor response under standard and reduced-contrast conditions. Results Irradiation at 10 Gy induced severe cone loss, resulting in mortality from 15 dpf. In contrast, larvae exposed to 8 Gy showed no significant alterations in central or dorsal cones compared with controls, whereas ventral cones were significantly shorter and fewer in number. These abnormalities, as well as eye size, gradually recovered to control levels by 21 dpf. Although transient reductions in eye size and ventral cones were observed, OMR testing revealed no impairment of visual performance at 8, 14, or 21 dpf, even under stringent low-contrast conditions. Discussion Sub-lethal gamma irradiation transiently induced localized damage especially in the ventral retina and reduction in eye size, both of which were fully repaired within 21 dpf. Behavioral analysis demonstrated that such transient, repairable damage does not impair visual function in irradiated medaka larvae.

Purpose Chironomus ramosus, an Indian tropical midge, exhibits remarkable tolerance to radiation and desiccation stress, making it an ideal model for studying cellular adaptive responses. The salivary gland (SG) cells of fourth instar larvae, known for their high metabolic activity, serve as a valuable system for investigating molecular mechanisms underlying stress response. This study aimed to investigate the significance of tropomyosin and actin in cellular recovery post gamma radiation exposure from salivary gland cells of Chironomus ramosus larvae in mediating the radiation-induced stress response. Materials and methods The SG cells were isolated from control and gamma-irradiated fourth instar larvae and subjected to metabolic labeling ([35S] methionine) to assess protein synthesis dynamics. Western blotting and immunofluorescence staining confirmed the radiation-induced expression of tropomyosin and actin following 2200 Gy gamma radiation exposure. Semi-quantitative RT-PCR was employed to confirm transcriptional upregulation of the target genes. Results Gamma radiation exposure triggered two to three-fold elevation in tropomyosin and actin protein levels in SG cells of Chironomus ramosus, with sustained upregulated expression through 24–48 h of post-irradiation recovery. The corresponding mRNA expression profiles paralleled these protein-level changes, reinforcing the notion of radiation-induced transcriptional regulation of cytoskeletal proteins in SG cells of C. ramosus. Conclusion This study provides compelling evidence that tropomyosin and actin stress fibers are overexpressed in C. ramosus larvae following gamma radiation exposure, suggesting a crucial role for cytoskeletal remodeling in radiation-induced adaptive responses.

Purpose: Radiotherapy is a widely used cancer treatment, and radiation-induced fibrosis is a frequent late effect that can significantly reduce patients’ quality of life. Many approaches for evaluating and grading radiation late damage, such as fibrosis, are based on semi-quantitative methods. This study aimed to characterize the histopathological changes associated with late radiation damage in mice after exposure to proton and photon irradiation, and to evaluate the applicability of stereological methods for quantitative assessment of these changes. Materials and Methods: A mouse leg model was used to evaluate and compare the potential radiation-induced functionality impairments with histopathological changes. Mice (n = 32) were subjected to a single high dose of photon (n = 18) or proton (n = 14) irradiation on the right foot, while the left, unirradiated leg served as a control. Late damage was assessed using a leg contracture assay, while histopathological changes were quantified using stereological point counting. Results: Proton- and photon-irradiated legs histologically showed a dose-dependent increase in connective tissue and epidermal thickness and reduced adipose tissue. Adipose tissue was replaced with connective tissue, adnexal structures disappeared, and the epidermis was altered. An association was found between leg contracture in the living mice and histopathological connective tissue changes, suggesting that fibrosis contributes to impaired joint mobility. However, discrepancies between histological findings and the leg contracture assay indicate that factors other than connective tissue changes, such as tendon damage and experimental uncertainties, influence joint movement. Conclusions: This study provides a quantitative approach for associating radiation effects in normal tissue with histopathological changes, offering a valuable model for investigating late radiation-induced damage. The study highlights the need for larger studies to fully elucidate the late side effects of proton and photon irradiation.

Purpose This review summarizes the discoveries of 8-bromopurine nucleosides (8-Br-Pu), particularly 8-bromo-2′-deoxyadenosine (8-Br-dA) and 8-bromo-2′-deoxyguanosine (8-Br-dG), in chemistry and biology over the past two decades. It compiles available data on the reactions of hydrated electrons (eaq –) with various 8-bromopurines, as determined by pulse radiolysis and supported by theoretical studies. Three distinct mechanistic pathways are identified: dissociative electron attachment, sequential electron transfer-proton transfer, and concerted electron-proton transfer. This review also highlights the use of 8-Br-dA and 8-Br-dG in the synthesis of a library of 5′,8-cyclopurine nucleosides (cPu) for quantifying them in genetic material and incorporating them into oligonucleotides (ODNs) for DNA repair research. Additionally, the summary covers the use of 8-Br-dA and 8-Br-dG embedded in various ODNs to study excess electron transfer (EET), their potential as radiosensitizers, and their formation in vivo via hypobromous acid. Conclusion Based on radiation chemistry, our understanding of the one-electron reduction of 8-Br-dA and 8-Br-dG has been enhanced substantially. This mechanistic background is crucial for a better understanding of and addressing their significant roles in the biological environment, such as DNA radiosensitizers for cancer radiation therapy or as biomarkers for early inflammation.

Purpose Understanding the energy-dependent variation in relative biological effectiveness (RBE) is crucial for both neutron radioprotection and therapeutic applications. This study aims to evaluate the biological impact of neutron irradiation on A375 human melanoma cells using neutron beams of different energy ranges, with the goal of contributing to the optimization of radioprotection standards and the advancement of neutron-based cancer therapies, such as Boron Neutron Capture Therapy (BNCT). Material and methods A375 human melanoma cells were irradiated using two distinct neutron beams: one in the keV range at the CNA facility in Sevilla, and another in the MeV range at the CIEMAT facility in Madrid. Clonogenic assays were performed to evaluate cellular response and determine RBE values. The biological effects were assessed and compared with previously obtained data from thermal-equivalent neutron energies and reference photon irradiation. Results The MeV-range neutron beam induced slightly stronger biological effects than the keV-range beam, but the observed RBE difference was notably smaller than the ∼50% gap predicted by ICRP models. Instead, the experimental trend closely aligned with previous theoretical RBE estimations based on secondary particle contributions. These results underscore the need to reevaluate current radioprotection weighting factors and support the refinement of neutron-based therapeutic protocols.

Purpose Based on the conserved features of radiation response, we integrated the human and plant genomes to identify human ionizing radiation-responsive genes, aiming to identify novel radiation indicators and develop dose reconstruction models for radiation exposure assessment. Methods and materials We proposed a method employing homologous gene comparisons between 53 plant species and human genomes to identify the potential human ionizing radiation-responsive genes. Multiple linear regression models (optimized via stepwise regression), lasso regression model, ridge regression model, and elastic net regression model were constructed to predict radiation doses based on the expression profiles of these genes from four independent datasets. Model training and validation were performed using the leave-one-out-cross-validation (LOOCV) approach. The predictive performances were evaluated using the correlation coefficient (R) and root mean square error (RMSE). Results We identified a total of 39 plant-based human ionizing radiation-responsive genes as potential radiation indicators, comprising 23 previously known human genes and 16 potential candidates derived from plants. The linear model outperformed the other three models in radiation dose reconstruction across multiple radiation exposure scenarios, as evaluated by the performance metrics R and RMSE. The dose reconstruction models achieved high predictive accuracy for radiation exposure doses in both training and test sets at different dose rate conditions and time points after irradiation. Conclusions In conclusion, we identified a panel of human ionizing radiation-responsive genes as promising indicators and developed dose reconstruction models with potential applications in radiation exposure assessment. These findings provide a new strategy for expanding the pool of human ionizing radiation biomarkers and hold promise for improving dose estimation during radiological emergencies.

Purpose Since its initial release, the aim of Biodose Tools was to offer an easy-to-use platform to perform the mathematical calculations needed in biological dosimetry. This update 3.7.1, mainly focuses on new features related to large-scale emergency responses, like criticality accidents dose estimation and laboratory networks. Material and Methods Biodose Tools has been developed using the R programming language. The current version (3.7.1) uses the same external dependencies as version 3.6.1 (released November 2022) while integrating three new external packages to support the new functionalities. Results Version 3.7.1 introduces different new modules: (a) a characteristic limits module that calculates decision thresholds and detection limits following ISO19238:2023 standards, and offers statistical tests to compare rates between suspected exposure cases and control data; (b) an enhanced dose estimation module which supports multiple dose assessments for dicentric and translocation assays for various exposure scenarios: acute, protracted, and highly protracted, as well as whole and partial-body exposures; (c) a criticality accidents module for multiple dose estimations using dicentrics in mixed gamma-neutron exposure scenarios (e.g. nuclear detonations); and (d) an Interlaboratory comparison module that automates the evaluation and comparison of dose estimates across laboratories. Conclusions Biodose Tools (https://www.reneb.net/software/) continues to evolve in response to the dynamic needs of the biological dosimetry community, contributing to the preparedness and consistency in emergency response and routine applications.

Purpose This study investigated whether strictly non-thermal, GSM-like 3.5 GHz radiofrequency electromagnetic fields (RF-EMF)—overlapping in frequency with bands used by 5 G networks but not employing a 5 G NR waveform—disrupt redox homeostasis and activate apoptotic signaling in peripheral sensory neurons. Materials and methods Primary mouse dorsal root ganglion (DRG) cultures were exposed in a GTEM-based setup to pulsed 3.5 GHz RF-EMF (217 Hz, ∼12.5% duty) for 1–24 h at 37 °C with <0.1 °C temperature difference between groups. Dosimetry confirmed non-thermal exposure with localized peaks consistent with IEEE/IEC guidance. Cell viability, reactive oxygen species (ROS), mitochondrial-apoptotic markers (Bax, Bcl-2, cytochrome c, caspase-3), and p75^NTR were quantified by blinded confocal analysis. Results RF-EMF caused a significant, time-dependent reduction in viability with robust ROS elevations; increased Bax and caspase-3; decreased Bcl-2; and cytochrome c release, with maximal effects at 12–24 h. p75^NTR upregulation indicated maladaptive neurotrophin signaling. Conclusions Under non-thermal conditions, 3.5 GHz RF-EMF perturbs redox balance and triggers mitochondria-dependent apoptosis in DRG neurons, highlighting peripheral neuronal vulnerability to mid-band exposures. These findings provide a mechanistic link between RF exposure and oxidative/apoptotic pathways and warrant in vivo studies assessing long-term and interventional outcomes.