Radiation Damage Research Articles

Most structure determinations using both X-rays and cryo-EM were carried out at cryogenic temperatures. It is therefore very likely that our current picture of protein structure has a bias towards these temperatures and in particular underrepresents energetically higher states. However, physiological processes typically take place at room temperature and above, where energetically higher-lying states and the resulting protein flexibility should play a major role. In addition to the impact on enzyme reactions themselves, this bias should also have a significant influence on ligand binding, as used, for example, in structure-based drug discovery. And indeed, there are some reports of different ligand binding behavior as a function of temperature.In order to systematically investigate the influence of temperature on ligand-binding in the context of structure-based drug discovery, we therefore carried out the same fragment screen under otherwise identical conditions, once with conventional rotational data collection at 100K and once with the method of fixed-target serial crystallography at room temperature. Serial crystallography should make it possible to significantly reduce the influence of radiation damage and the associated loss of resolution by distributing the dose across thousands of crystals, compared to single- crystal measurements.We selected the fosfomycin resistance protein FosAKP as target protein and performed a screen against the f2X entry library containing 95 fragments. Interestingly, we were able to achieve almost the same resolution in the serial crystallography experiments at room temperature as with single-crystal measurements at room temperature. Compared to the serial measurements, single-crystal measurements at room temperature provided a 0.3 - 0.4 angstrom worse resolution.The presentation will cover both the methodological aspects of fixed-target serial crystallography at room temperature and also discuss the results of the screen at the two different temperatures in relation to structure-based drug discovery.

Serial crystallography is an important technique with unique abilities to resolve enzymatic transition states, minimize radiation damage to sensitive metalloenzymes, and perform de novo structure determination from micron sized crystals. This technique requires the merging of data from thousands of crystals, making manual identification of errant crystals infeasible. cctbx.xfel.merge uses filtering to remove problematic data. However, this process is imperfect, and data reduction must be robust to outliers. We add robustness to cctbx.xfel.merge at the step of uncertainty determination for reflection intensities. This step is a critical point for robustness because it is the first step where datasets are considered as a whole, as opposed to individual lattices. Robustness is conferred by reformulating the error calibration procedure to have fewer and less stringent statistical assumptions and incorporating the ability to down weight low quality lattices. We then apply this method to five macromolecular XFEL datasets and observe improvements to each. The appropriateness of the intensity uncertainties is demonstrated through internal consistency. This is performed through theoretical CC ½ and I/σ relationships and by weighted second moments, which use Wilson's prior to connect intensity uncertainties with their expected distribution. This work presents new mathematical tools to analyze intensity statistics and demonstrates their effectiveness through the often underappreciated process of uncertainty analysis.

Isolated radiation damage created along un-etchable tracks in PADC consists of two hydroxyl groups

Low frequency band pass Fourier filtering for irradiation damage analysis in the transmission electron microscope.

Implementation of dry storage models in Falcon: cladding creep, annealing of cladding irradiation damage, and fuel helium-swelling

Irradiation damage of zirconium carbide with different stoichiometry

5-Androstenediol esters, dibutanoate and dipropionate, were synthesized as prototypes of effective cytoprotectors with prolonged action. The cytoprotective effect of the new 5-androstenediol derivatives was assessed in human lung and skin fibroblasts and human blood mononuclear cells exposed to UV radiation. 5-Androstenediol esters showed a regenerating, cytoprotective effect on different types of fibroblasts, but not on human peripheral blood mononuclear cells. The DNA comet assay revealed no genotoxic effect of the new steroids on the mononuclear fraction of human blood, which indicates their safety. The cytoprotective activity of 5-androstenediol dibutanoate and dipropionate in human fibroblasts attests to their possible use for creating ointments and liniments for the treatment of skin injuries requiring regeneration (including irradiation damage).

Organic phosphates are a class of compounds containing the (P═O) group, which hold substantial importance in environmental, chemical, and biological research. Studying electron scattering from organophosphates will deepen our understanding of how ionizing radiation affects living tissues, particularly the damage to DNA components through complex bond breakages. This theoretical work examines the electron scattering cross sections for monomethyl phosphate, dimethyl phosphate, trimethyl phosphate, monoethyl phosphate, diethyl phosphate, and triethyl phosphate molecules within the fixed-nuclei approximation. These targets were chosen primarily for their importance and also for being the smallest organophosphates in molecular weight. The study also helps to understand the effects of isomerism and target electron count on cross sections. Previous studies on electron collisions with these molecules are incomplete, which motivated us to perform these calculations. In the present study, we computed electron impact total, elastic, inelastic, momentum transfer, ionization, and differential elastic cross sections using the optical potential approach in the energy range from the ionization potential to 5000 eV. The results are then compared with the previously available experimental and theoretical results. The cross sections presented in this study will help model radiation damage and understand the chemistry of organophosphates.

Proton-transfer dynamics in hydrogen-bonded dimers are important for understanding debated mechanisms of radiation damage to DNA base pairs. Using coincidence photofragment imaging in ultrafast extreme-ultraviolet pump and near-IR probe experiments on the formic acid dimer, we observed a transient enhancement (150 fs) of the protonated monomer signal. This correlates with ab initio molecular dynamics simulations of the ionization induced dynamics, showing concerted proton transfer and dimer ring opening in a metastable dimer. Coincidence analysis revealed the ultraslow mechanism of the metastable dimer cation on the microsecond time scale. The ultraslow dynamics were attributed to a barrier for the structural rearrangement of the deprotonated moiety from an HCOO to an OCOH geometry. Moreover, ultraslow channels of protonated monomer ions to form H3O+ + CO and H2O + CHO+ were observed and interpreted as dissociation of hot photoions, involving nontrivial hydrogen migration.

Serial femtosecond X-ray crystallography (SFX) captures the structure and dynamics of biological macromolecules at high spatial and temporal resolutions. The ultrashort pulse produced by an X-ray free-electron laser (XFEL) `outruns' much of the radiation damage that impairs conventional crystallography. However, the rapid onset of `electronic damage' due to ionization limits this benefit. Here, we distinguish the influence of different atomic species on the ionization of protein crystals by employing a plasma code that tracks the unbound electrons as a continuous energy distribution. The simulations show that trace quantities of heavy atoms (Z > 10) contribute a substantial proportion of global radiation damage by rapidly seeding electron ionization cascades. In a typical protein crystal, sulfur atoms and solvated salts induce a substantial fraction of light-atom ionization. In further modeling of various targets, global ionization peaks at photon energies roughly 2 keV above inner-shell absorption edges, where sub-2 keV photoelectrons ejected from these shells initiate ionization cascades that are briefer than the XFEL pulse. These results indicate that relatively small quantities of heavy elements can substantially affect global radiation damage in XFEL experiments.

Magnetic resonance techniques are powerful, nondestructive, non-invasive tools with broad applications in radiation dosimetry. Electron paramagnetic resonance (EPR) enables direct quantification of dose-dependent radiation-induced paramagnetic defects, while nuclear magnetic resonance (NMR) reflects the influence of such defects through changes in line width and nuclear spin relaxation. To date, these methods have typically been applied independently. Their combined use to probe radiation damage in the same material offers new opportunities for comprehensive characterization and preferred dosimetry techniques. In this work, we apply both EPR and NMR to investigate radiation damage in lithium carbonate (Li2CO3). A detailed EPR analysis of γ-irradiated samples shows that the concentration of paramagnetic defects increases with dose, following two distinct linear regimes: 10–100 Gy and 100–1000 Gy. A gradual decay of the EPR signal was observed over 40 days, even under cold storage. In contrast, 7Li NMR spectra and spin–lattice relaxation times in Li2CO3 exhibit negligible sensitivity to radiation doses up to 1000 Gy, while 1H NMR results remain inconclusive. Possible mechanisms underlying these contrasting behaviors are discussed.

Ionizing radiation exposure, whether from accidental incidents, radiation therapy, or radiological weapons, poses a significant risk to public health and military personnel. Survivors experience both acute and chronic physiological effects, including tissue dysfunction, fibrosis, and impaired organ function. Among affected tissues, skeletal muscle is particularly vulnerable, as radiation damages muscle precursor cells (MPCs), impairing their ability to regenerate and maintain muscle homeostasis. Extracellular vesicles (EVs), nano-sized lipid-bound vesicles released by cells, mediate intercellular communication by transferring bioactive molecules such as proteins, lipids, and microRNAs. EVs derived from MPCs have shown promise in promoting muscle regeneration, yet their role in radiation injury remains unclear. This study investigated whether EVs from healthy MPCs (NoRad-EVs) could improve cell function in irradiated cells compared to EVs from irradiated MPCs (Rad-EVs). Our findings demonstrated that viability and proliferation are improved in irradiated MPCs receiving NoRad-EVs whereas Rad-EVs fail to mitigate radiation-induced damage. Specifically, NoRad-EVs increased MPC viability from 52 ± 5.7% to 71 ± 4.9% and improved BrdU-measured proliferation by ~ 16% compared to untreated irradiated controls. NoRad-EVs also enhanced angiogenesis in human umbilical vein endothelial cells (HUVECs) and microvascular fragments (MVFs). HUVECs treated with NoRad-EVs showed significantly greater tube branching length (~ 1.5-fold increase) compared to cells exposed to Rad-EVs. Similarly, MVFs receiving NoRad-EVs treatment exhibited a ~ 3-fold increase in vessel density after 7 days as opposed to the group cultured with Rad-EVs. Differential miRNA expression analysis revealed significant alterations in Rad-EVs compared to NoRad-EVs, affecting key pathways related to muscle repair, angiogenesis, and oxidative stress response. Thirteen miRNAs were downregulated and seven were upregulated in Rad-EVs compared to NoRad-EVs (fold change ≥ 1.3, p < 0.05), including targets involved in VEGF, PI3K-Akt, and FoxO signaling. This research underscores the need for effective countermeasures against radiation-induced injuries, which have detrimental effects on the pro-angiogenic and proliferative functions of MPCs and their secreted EVs. Overall, these promising in vitro findings support the restorative impacts of NoRad-EVs as a potential therapeutic, including miRNA-enriched vesicles, in mitigating radiation-induced muscle injury, particularly in the context of military medicine and radiological emergencies.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-15699-x.

Methylation of DNACpG domains in cellular DNA is a key mechanismof epigenetic regulation. Disruptions in the processes maintainingDNA methylation can lead to diseases like cancer. The radiation responseof certain cancer cells may be affected by their DNA methylation levels,which may have consequences in their response to radiotherapy. Inthis work, we utilized DNA origami nanotechnology to examine whetherDNA methylation impacts DNA response to ionizing radiation in solutionbefore biological processes come into play. Our findings reveal thata protective effect is achieved with just a few methylated CpG adducts.Both low-LET (electron) and high-LET (carbon ion) irradiation showa reduced lesion count in methylated DNA, as indicated by qPCR results.AFM single-molecule observations using DNA origami nanoframes suggestfewer double-strand breaks in methylated DNA after carbon ion irradiation.This radioprotective effect may contribute to the differential radiationresponse of cellular DNA and should be considered when predictingand evaluating DNA radiation damage yields.

Processed-kaolin particle film can mitigate solar radiation damage in young Atlantic Forest species

In a recent multicenter analysis of 454 patients undergoing post-prostatectomy salvage radiotherapy, the open surgical approach, as opposed to minimally invasive surgery, emerged, unexpectedly, as the strongest predictor of acute gastrointestinal and genitourinary toxicity. Patients treated with laparoscopic or robotic prostatectomy experienced significantly lower rates of ≥grade 2 toxicity compared to those who had undergone open retropubic surgery, irrespective of total dose, treatment margins, or radiation delivery platform. This finding, which to our knowledge has not been previously reported, raises the hypothesis that surgical technique leaves a lasting biological imprint on irradiated tissues. Drawing on current knowledge in radiobiology, cytokine signaling, wound healing, and pelvic dosimetry, we explore potential mechanisms by which open surgery may create a more hypoxic, inflamed, and fibrotic microenvironment, thereby amplifying radiation damage. We further discuss how target volume margins may biologically interact with this tissue state to increase normal tissue exposure. This Perspective aims to provide a conceptual framework for understanding this unexpected association, highlighting its clinical relevance for individualizing margins, counselling high-risk patients, and designing future studies at the interface of surgery and radiation oncology. This paper does not introduce additional patients or statistical models; instead, it offers an in-depth clinical and mechanistic interpretation of previously published ICAROS findings.

Objective.FLASH radiotherapy is a promising technique based on the delivery of ultra-high dose rates (UHDR) to spare healthy tissue. Robust quality assurance (QA) is required to ensure a safe delivery of the treatment. QA devices such as phantoms and ionization chambers (ICs) are typically made out of polymeric materials to ensure water equivalence. However, radiation exposure, particularly at UHDR where achieving high doses is easier, may cause irreversible changes to the structure of these materials. Such extreme conditions can, for example, induce microstructural defects that may lead to mechanical failure or alter electrical properties such as the dielectric permittivity or conductivity, potentially compromising the calibration and reliability of critical QA devices, such as ICs. This study aims to characterize radiation damage in common materials used for QA devices and identify which of them can withstand these challenging conditions.Approach.A variety of materials commonly used in phantoms and ICs, with diverse characteristics (transparent, opaque, conductive and non-conductive) were irradiated using 68 MeV proton and 20 MeV electron beams, reaching doses up to 1 MGy under UHDR conditions (average dose rates of 100-500 Gy s-1). Material damage was evaluated through optical, chemical, mechanical and electrical tests to quantify change in color, structural integrity, and relevant electrical properties such as conductivity and dielectric constant that can affect detector response.Main Results.External appearance of some materials significantly changed after irradiation. All transparent materials exhibited change in color post-irradiation. Chemical analyses conducted after irradiation and repeated two years later indicated partial recovery in some materials. No significant difference in damage was observed between proton and electron irradiation, suggesting comparable radiation damage mechanisms. Dose rate alone did not exacerbate damage beyond total dose effects; however, extended irradiation at high dose rates resulted in thermal damage under some conditions. Mechanical testing revealed increased fragility, changes in hardness and dimensions, while some materials experienced significant changes in dielectric constant and conductivity.Significance.Materials such as Polymethyl Methacrylate (PMMA), PC, Polyoxymethylene (POM), and its conductive variant POM ELS, are unsuitable for prolonged irradiations at UHDR due to significant structural degradation observed. For see-through phantom construction, CPS offers a more durable alternative to PMMA. For detector construction, PEEK (for non-conductive parts) and graphite (for conductive parts) demonstrated promising durability, making them preferable choices under high dose and UHDR conditions. The higher stability of these materials can be attributed to the presence of aromatic rings in their chemical structure, which enhances radiation resistance.

Thermally activated annealing in semiconductors faces inherent limitations, such as dopant diffusion. Here, a nonthermal pathway is demonstrated for a complete structural restoration in predamaged germanium via ionization-induced recovery. By combining experiments and modeling, this study reveals that the energy transfer of only 2.4keV nm-1 from incident ions to target electrons can effectively annihilate pre-existing defects and restore the original crystalline structure at room temperature. Moreover, it is revealed that the irradiation-induced crystalline-to-amorphous (c/a) transformation in Ge is reversible, a phenomenon previously considered unattainable without additional thermal energy imposed during irradiation. For partially damaged Ge, the overall damage fraction decreases exponentially with increasing fluence. Surprisingly, the recovery process in preamorphized Ge starts with defect recovery outside the amorphous layer and a shrinkage of the amorphous thickness. After this initial stage, the remaining damage decreases slowly with increasing fluence, but full restoration of the pristine state is not achieved. These differences in recovery are interpreted in the framework of structural differences in the initial defective layers that affect recovery kinetics. This study provides new insights on reversing the c/a transformation in Ge using highly-ionizing irradiation and has broad implications across materials science, radiation damage mitigation, and fabrication of Ge-based devices.

BackgroundRadiation-induced nephropathy is a major concern, particularly for patients undergoing radiotherapy. This study investigates melatonin’s (MEL) protective effects against kidney damage induced by Flattening Filter (low dose rate-LDR) and Flattening Filter Free (high dose rate-HDR) X-ray by focusing on apoptosis and SIRT1 modulation in rats.MethodsForty rats were divided into five groups (n = 8): Group 1 (control), Group 2 (FF-LDR, 400MU/min), Group 3 (MEL + FF-LDR), Group 4 (FFF-HDR, 1400MU/min), and Group 5 (MEL + FFF-HDR). Groups 3 and 5 received 10 mg/kg MEL intraperitoneally 15 min before an 8 Gy abdominal irradiation. Rats were sacrificed 48 h post-radiotherapy for histopathological and immunohistochemical analyses of the kidney.ResultsThe FFF-HDR group showed fewer atypical glomeruli and lost brush borders, and epithelial connections compared to the FF-LDR group. The MEL + FFF-HDR group had significantly fewer atypical glomeruli and brush border losses than the MEL + FF-LDR group. Additionally, while SIRT1 expression increased in both the FF and FFF groups following MEL treatment, this increase was significant only in the MEL + FFF-HDR group compared to the control group. MEL pretreatment effectively decreased cellular apoptosis in both MEL + FFF-HDR and MEL + FF-LDR groups.ConclusionsMelatonin has been proven to be an effective radioprotective agent against renal nephropathy and cellular apoptosis induced by FF and FFF beams. Additionally, pre-treatment with MEL has been shown to enhance SIRT1 expression, thereby protecting the kidneys from acute radiation damage, particularly from high-dose rate radiation.

Spatially fractionated radiation therapy (SFRT) delivers heterogeneous dose distributions to enhance tumor control while reducing normal tissue toxicity. Since conventional models like the linear-quadratic (LQ) model overlook intercellular signaling, a key factor in non-uniform fields, this study uses an advanced mathematical model to assess its impact on SFRT plan evaluation. A volumetric-modulated arc therapy (VMAT)-based SFRT framework was developed, resulting in two treatment plans: VMAT-GRID and 3D lattice radiation therapy (3D-LRT). A kinetic model incorporating both direct radiation damage and intercellular signaling was implemented to simulate signal dynamics, DNA damage, and calculate the survival ratio across 3D voxelized volumes. Key dosimetric and biological indices, including mean dose, equivalent uniform dose (EUD), valley-to-peak dose ratio (VPDR), therapeutic ratio (TR), and normal tissue complication probability (NTCP), were computed using both physical and biological doses. Incorporating intercellular signaling led to increased EUD, mean dose, VPDR, and NTCP, particularly in 3D-LRT plans with steeper dose gradients. Additionally, signaling effects caused extra biological damage in non-irradiated cells within low-dose regions, which resulted in a decreased TR. This study highlights that accounting for radiation-induced signaling alters the evaluation of SFRT plans compared to models considering only direct radiation effects. Therefore, to achieve accurate assessment, particularly in complex techniques like 3D-LRT, it is advisable to employ models capable of capturing both direct and indirect radiation responses. Additionally, experimental validation is a crucial step toward translating this model into clinical practice.

Abstract The objective of the present study is to investigate the hardening behavior, superelastic recovery, and structural properties of NiTi Shape Memory Alloy (SMA) after 10 MeV high-energy Fe+ ion irradiation to damage levels of 1.2 and 6.0 d.p.a (displacements per atom). According to Stopping and Range of Ions in Matter (SRIM) calculations, Secondary Ion Mass Spectroscopy (SIMS) analysis, and Transmission Electron Microscopy (TEM) imaging, a 3-micron irradiation layer was obtained with an amorphous structure; the maximum values of damage and Fe+ ion concentration occurred at 2.4 and 2.7 microns, respectively. The mechanical response was characterized in two-direction nanoindentation tests: parallel and perpendicular to the ion beam direction. Cross-sectional nanoindentation indicates that the maximum hardening corresponds to the maximum of the Fe+ ion concentration; the maximum hardness was found at 2.7 microns for both d.p.a. levels. The changes in superelastic properties were achieved in the amorphous layer that suppressed the B2-B19′ phase transformation at a sub-micron scale. We show that cross-sectional nanoindentation is an appropriate method for determining the subtle micromechanical property changes in near-surface regions. It also allows the material and structural properties at a selected point in the non-homogeneous irradiated layer to be correlated with the local level of irradiation damage or ion concentration. This is very important in the development of SMAs and their applications in nuclear technologies.