Search Results (66)

The Fukushima nuclear accident highlighted that evacuation-related psychosocial harm can outweigh direct radiation risks, underscoring the need to define the health impacts of chronic low-dose-rate (LDR) radiation and evidence-based thresholds for intervention. This study investigated the effects of continuous, postnatal LDR gamma irradiation (1.2 mGy/h, cumulative dose: 5 Gy) in male mice. While no changes in body weight, hippocampal neurogenesis, or major glial and neuronal populations were observed, persistent DNA damage (γ-H2AX foci) in dentate gyrus granule cells occurred in both irradiated male and female mice. Irradiated male mice developed anxiety-like behaviour, a phenotype not observed in a previously published study of female mice subjected to an identical irradiation protocol. Molecular profiling revealed two novel, dysregulated miRNA/mRNA axes in the hippocampus linking DNA damage to behaviour: a maladaptive miR-466i-5p/Tfcp2l1 pathway associated with genomic instability, and a potentially adaptive miR-101a-5p/BMP6 pathway promoting neuronal survival. Venn analysis further identified miR-124b-3p and novel-miR489-3p as conserved exposure biomarkers, altered in both the hippocampus and blood of irradiated animals. Our results show that a high cumulative dose of chronic LDR induces markedly less severe hippocampal pathology than has been reported for equivalent acute doses. These findings support the concept of dose-rate-dependent threshold dose and contribute to the evidence base for developing countermeasures following nuclear incidents or other radiation exposures. Full article

The aim of the study was to define radiobiological effects of single and fractionated low doses in normal fibroblasts in 40 patients with squamous cell carcinoma of the head and neck (HNSCC) treated with induction chemotherapy combined with low-dose fractionated radiation (LDFR) and to answer the question regarding the role of low-dose hyper-radiosensitivity (HRS) in these effects. HRS status was determined using flow cytometry-based clonogenic survival assay (cells were irradiated with doses 0.1–4 Gy of 6 MV X-rays). Radiobiological effects (cell kill, kinetics of DSB recognition and repair, chemopotentiation) of LDFR 4x0.5 Gy and a single dose of 2, 0.5 and 0.2 Gy were estimated by clonogenic, pATM and γH2AX foci assays. HRS response was demonstrated for normal fibroblasts in 6 of the 40 HNSCC patients. For all assessed biological parameters, significant interindividual differences were observed. The presence of HRS had no effect on the chemopotentiating effects of LDFR 4x0.5 Gy, which were similar to that after 2 Gy. There was also no association between HRS and the maximum number of pATM and γH2AX foci induced by single (0.2, 0.5, 2 Gy) or fractionated low doses 4x0.5 Gy. Significantly higher percentages of residual pATM and γH2AX foci observed after LDFR 4x0.5 Gy than after 2 Gy were independent of HRS. HRS is a rare finding (15%) in normal fibroblasts from HNSCC patients; therefore, it is of rather little importance in healthy late-reacting connective tissues. Moreover, the fibroblast response to single and fractionated low doses (alone or in combination with carboplatin and paclitaxel) appeared more dependent on individual radiosensitivity than on HRS. Full article

Proton therapy offers superior dose localization, yet the biological effects of low-energy protons relevant to superficial tissues remain underexplored. We report the design and validation of a proton irradiation setup developed at the Tandem Accelerator of NCSR “Demokritos” for controlled radiobiological experiments. Monte Carlo simulations using Geant4 and Monte Carlo Damage Simulation (MCDS—Monte Carlo Damage Simulation) were used to determine proton energy spectra, linear energy transfer (LET), and predicted DNA damage yields. A single layer (15–20 μm in thickness) of human keratinocytes (HaCaT) was irradiated at doses from 0.65 to 3.65 Gy, and γ-H2AX foci were quantified as markers of tracks including one or more DNA double-strand breaks. The system achieved a uniform dose rate of 0.37 Gy/min, as calculated with Geant4, with a mean proton energy of 4.1 MeV (LET ≈ 8 keV/μm). A strong correlation (R² = 0.93) was observed between proton dose and γH2AX foci per nucleus (~10 foci/Gy), reflecting damage-inducing proton tracks rather than individual DNA double-strand breaks. At higher doses, an increased fraction of cells exhibited pan-nuclear γH2AX staining, characterized by a diffuse γH2AX signal throughout the nucleus and commonly associated with extensive or clustered DNA damage and global chromatin phosphorylation. These responses are consistent with the well-established dense ionization patterns produced by low-energy protons, as indicated by the LET spectrum and supported by MCDS-predicted clustered damage yields. While the γH2AX assay does not directly resolve simple versus complex DNA lesions, the agreement between Monte Carlo modeling and the observed cellular stress responses indicates that the irradiation platform reliably reproduces the expected biological signatures of low-energy proton exposure. Consequently, the developed system provides a robust experimental tool for systematic investigations of cellular radiosensitivity and radiotoxicity, with potential applications in skin dosimetry and radioprotection. Full article

Low-voltage instrumentation and control (I&C) cables in nuclear power plants are continuously exposed to gamma (γ) radiation within containment areas, leading to cumulative degradation of their polymer insulation over decades of operation. Since conventional mechanical aging assessments are destructive, this study establishes a non-destructive diagnostic framework using high-frequency dielectric spectroscopy. Cable samples with ethylene propylene rubber (EPR) insulation and chlorosulfonated polyethylene (CSPE) jackets were subjected to controlled γ-irradiation at doses up to 1200 kGy. The broadband dielectric response was analyzed along with derived novel diagnostic parameters from capacitance and loss tangent spectra and a machine learning AI algorithm. The results show a strong, material-dependent relationship between radiation dose and dielectric indicators. For EPR insulation, the central capacitance (CC) and (C × F × LF) exhibit high positive sensitivity for Black and White EPR materials, respectively, whereas for CSPE jackets, the central frequency (CF) shows a pronounced monotonic decrease with the radiation exposure. These findings enable a straightforward, transparent interpretation of dielectric data and implement a new, accurate method of irradiated cables diagnosis. Full article

This paper investigates the degradation characteristics of a DC/DC converter operating under cold redundancy conditions when subjected to total ionizing dose (TID) effects. An optimized RCC isolated auxiliary power supply circuit was evaluated through ⁶⁰Co γ-ray irradiation up to 100 krad(Si) at dose rates of 3.89, 8.89, and 13.89 rad (Si)/s, with electrical characterizations performed at both the system level and the device level, focusing on the critical VDMOS transistors. The results indicate that the main output voltage and conversion efficiency remain essentially stable after irradiation, whereas the auxiliary supply voltage and efficiency degrade significantly, leading to a pronounced reduction in the controller supply margin. Device-level measurements reveal a negative threshold voltage shift of approximately 0.5–1.0 V with clear dose-rate dependence, while the subthreshold swing shows no obvious variation, suggesting that the degradation is primarily dominated by oxide-trapped charge effects. In addition, a substantial increase in drain current at low gate voltages is observed, which may further exacerbate restart risks under cold redundancy conditions. These findings demonstrate that the auxiliary power supply and startup margin constitute critical vulnerability points of cold-redundant DC/DC converters under TID stress and should therefore be primary targets for radiation-hardened design. Full article

Background: In nuclear medicine, numerous cancer types are treated via internal irradiation with radiopharmaceuticals, including low-LET (linear energy transfer) beta-emitting radionuclides like Lu-177. In most cases, such treatments lead to low-dose exposure of organ systems with β-irradiation, which induces only few isolated DSBs (double-strand breaks) in the nuclei of hit cells, the most threatening DNA damage type. That damaging effect contrasts with the clustering of DNA damage and DSBs in nuclei traversed by high-LET particles (α particles, ions, etc.). Methods: After in-solution β-irradiation for 1 h with Lu-177 leading to an absorbed dose of about 100 mGy, we investigated the spatial nano-organization of chromatin at DSB damage sites, of repair proteins and of heterochromatin marks via single-molecule localization microscopy (SMLM) in PBMCs. For evaluation, mathematical approaches were used (Ripley distance frequency statistics, DBScan clustering, persistent homology and similarity measurements). Results: We analyzed, at the nanoscale, the distribution of the DNA damage response (DDR) proteins γH2AX, 53BP1, MRE11 and pATM in the chromatin regions surrounding a DSB. Furthermore, local changes in spatial H3K9me3 heterochromatin organization were analyzed relative to γH2AX distribution. SMLM measurements of the different fluorescent molecule tags revealed characteristic clustering of the DDR markers around one or two damage foci per PBMC cell nucleus. Ripley distance histograms suggested the concentration of MRE11 molecules inside γH2AX-clusters, while 53BP1 was present throughout the entire γH2AX clusters. Persistent homology comparisons for 53BP1, MRE11 and γH2AX by Jaccard index calculation revealed significant topological similarities for each of these markers. Since the heterochromatin organization of cell nuclei determines the identity of cell nuclei and correlates to genome activity, it also influences DNA repair. Therefore, the histone H3 tri methyl mark H3K9me3 was analyzed for its topology. In contrast to typical results obtained through photon irradiation, where γH2AX and H3K9me3 markers were well separated, the results obtained here also showed a close spatial proximity (“co-localization”) in many cases (minimum distance of markers = marker size), even with the strictest co-localization distance threshold (20 nm) for γH2AX and H3K9me3. The data support the results from the literature where only one DSB induced by low-dose low LET irradiation (<100 mGy) can remain without heterochromatin relaxation for subsequent repair. Full article

Protons are conventionally regarded as a low-linear energy transfer (low-LET) radiation modality with a relative biological effectiveness (RBE) of 1.1, suggesting direct mechanistic similarity to X-rays in the underpinning biological effects. However, exposure to spread-out Bragg peak (SOBP) protons reveals instructive deviations from this assumption. Indeed, proton beams have a maximum LET of ~5 keV/µm but display reduced reliance on classical non-homologous end joining (c-NHEJ) as well as an increased dependence on homologous recombination (HR) and alternative end joining (alt-EJ). These features are well described in cells exposed to high-LET radiation and typically manifest between 100 and 150 keV/µm. We hypothesized that this apparent discrepancy reflects biological consequences of proton-beam properties that remain uncharacterized. In the present study, we outline exploratory experiments aiming at uncovering such mechanisms. We begin by investigating for both entrance and SOBP protons the dose-dependent engagement of HR we recently showed for X-rays. Consistent with our previous findings with X-rays, HR engagement after exposure to both types of proton beams declined with dose, from ~80% at 0.2 Gy to less than 20% at higher doses. RAD51/γH2AX foci ratios, reflecting HR engagement, were modestly higher following proton irradiation, in line with increased HR utilization. G₂-checkpoint activation, previously linked to HR, was also stronger after exposure to protons, as was DNA end resection. Moreover, the formation of structural chromosomal abnormalities (SCAs) was higher for SOBP than entrance protons and X-rays. Collectively, our results suggest quasi-high-LET characteristics for proton beams and raise the question as to the physical proton properties that underpin them. We discuss that the commonly employed definition of LET may be insufficient for this purpose. Full article

Radiotherapy (RT) is a standard treatment for cervical cancer, but its efficacy is often limited by tumor hypoxia and low radiosensitivity. Radiosensitizers that enhance RT without dose escalation are therefore of clinical interest. Alpha-mangostin (AM), a xanthone from Garcinia mangostana, exhibits anticancer and ROS-inducing properties. This study evaluated whether AM enhances radiosensitivity in vitro. Cytotoxicity (0–35 µM) was assessed by the MTT assay, and radiation sensitivity (0–6 Gy) was assessed by clonogenic survival. γ-H2AX immunofluorescence, cell cycle distribution, apoptosis induction, and clonogenic survival assessments were used to investigate the radiosensitization effect. AM showed dose-dependent cytotoxicity in HeLa cells at an inhibitory concentration 20 (IC20) of 13.67 µM while sparing fibroblasts. The radiation lethal dose 20 (LD20) was 1.4 Gy. However, combination treatment used AM at 12 µM (IC14) combined with 2 Gy (LD30) irradiation to avoid 50% cell death. AM enhanced G2/M arrest by 21.10% (p < 0.01) versus controls. In combination treatment, AM significantly increased γ-H2AX-positive cells to 48.2% (p < 0.0001), elevated apoptosis to 39.48% (p < 0.0001), and decreased clonogenic survival to 28% (p < 0.0001) compared with control. A combination index of about 0.9 indicated synergism. Therefore, AM effectively radiosensitized HeLa cells via increased DNA double-strand breaks and G2/M arrest. Full article

An open question in radiobiology concerns whether low doses of radiation are harmful or if cells are able to tolerate such exposure with minimal or no disruption. This issue is relevant for evaluating public health risks associated with the increasing number of medical computed tomography (CT) diagnostic procedures. This study evaluated the impact of CT scan-level exposure on human adipose mesenchymal stem cells (hMSCs) by measuring DNA damage responses (γH2AX, 53BP1, pATM foci), proliferation (Ki-67), senescence (β-galactosidase), and multiple gene expressions. Responses to one or five CT exposures were compared to a 2 Gy X-ray dose at intervals from 1 h to 10 passages post-irradiation. It was shown that CT scan briefly increased DNA damage markers but showed no significant long-term effects. A high dose of 2 Gy X-ray exposure caused sustained DNA damage, decreased proliferation, increased senescence, and significant changes in hundreds of genes even after several cell generations. After a single CT exposure, gene expression changes were minimal, while high-dose exposure led to strong activation of DNA repair and stress response pathways. Five CT scans caused a slight activation of LIF and HSPA1B genes, but these effects were minor compared to the high-dose group. All detected effects from CT scans were not observed by ten cell passages, whereas high-dose effects persisted. In conclusion, typical CT scan exposures have only short-term, mild effects on hMSCs, while high-dose radiation causes lasting cellular and genetic changes. Full article

Platinum-based radiochemotherapy is associated with hematologic side effects, impacting patient outcomes. However, the clinical mechanisms of cisplatin and its interaction with ionizing radiation (IR), including in biodosimetry for radiotherapy, have not yet been fully clarified. For this purpose, healthy donors’ peripheral blood lymphocytes (PBLs) were pretreated with cisplatin in a pulse (1–4 h) or continuous (24 h) regimen followed by X-rays. DNA damage was assessed as DNA double-strand breaks using repair foci of γH2AX and 53BP1 after 0.5 h and 24 h in G1 PBLs and a proliferation-based cytokinesis-block micronucleus assay. Additionally, cell death and proliferation activity were measured. Unlike a 1 h pulse, a 24 h cisplatin pretreatment caused a concentration-dependent increase in cisplatin-induced foci while decreasing IR-induced foci, especially 24 h after irradiation. This was accompanied by increased apoptosis, with cisplatin and IR having additive effects. Both genotoxins alone caused a dose-dependent increase in micronuclei, while cisplatin significantly reduced binuclear cells, especially after the 24 h treatment, leading to lower micronuclei frequencies post-irradiation. Our results show that prolonged cisplatin exposure, even at low concentrations, impacts the vitality and division activity of PBLs, with significantly stronger effects post-irradiation. This has major implications and must be considered for the detection of DNA damage-associated biomarkers in PBLs used in clinical prediction or biodosimetry during radiotherapy. Full article

To understand the biological effects of residual radioactivity after the atomic bomb explosion in Hiroshima and Nagasaki, we previously investigated the effects of ⁵⁶Mn, a major residual radioisotope. Our rat study demonstrated that inhalation exposure to ⁵⁶MnO₂ microparticles affected gene expression in the lungs, testes, and liver, despite the low radiation doses. Because ⁵⁶Mn is a β- and γ-emitter, the differential effects between β- and γ-rays should be clarified. In this study, ³¹Si, a β-emitter with a radioactive half-life similar to that of ⁵⁶Mn, was used to determine its effects. Male Wistar rats were exposed to sprayed neutron-activated ³¹SiO₂ microparticles, stable SiO₂ microparticles, or X-rays. The animals were examined on days 3 and 14 after irradiation. The expression of radiation-inducible marker genes, including Ccng1, Cdkn1a, and Phlda3, was measured in the spleen, lungs, and liver. Furthermore, the expressions of pathophysiological marker genes, including Aqp1, Aqp5, and Smad7 in the lungs and Cth, Ccl2, and Nfkb1 in the liver, were determined. Impacts of ³¹SiO₂ exposure were observed mainly in the liver, where the expression of Cth markedly increased on post-exposure days 3 and 14. Our data suggest that internal exposure to β-emitted microparticles has significant biological effects and its possible roles as residual radiation after atomic bombing. Full article

Our previous study demonstrated that the acute high-dose-rate (3.3 Gy/min) γ-ray irradiation (γ-irradiation) of postnatal day-3 (P3) mice with 5 Gy induced depression and drastic neuropathological changes in the dentate gyrus of the hippocampus of adult mice. The present study investigated the effects of chronic low-dose-rate (1.2 mGy/h) γ-irradiation from P3 to P180 with a cumulative dose of 5 Gy on animal behaviour, hippocampal cellular change, and miRNA and mRNA expression in the hippocampus and blood in female mice. The radiation exposure did not significantly affect the animal’s body weight, and neuropsychiatric changes such as anxiety and depression were examined by neurobehavioural tests, including open field, light-dark box, elevated plus maze, tail suspension, and forced swim tests. Immunohistochemical staining did not detect any obvious loss of mature and immature neurons (NeuN and DCX) or any inflammatory glial response (IBA1, GFAP, and PDGFRα). Nevertheless, γH2AX foci in the stratum granulosum of the dentate gyrus were significantly increased, suggesting the chronic low-dose-rate irradiation induced persistent DNA damage foci in mice. miRNA sequencing and qRT-PCR indicated an increased expression of miR-448-3p and miR-361-5p but decreased expression of miR-193a-3p in the mouse hippocampus. Meanwhile, mRNA sequencing and qRT-PCR showed the changed expression of some genes, including Fli1, Hs3st5, and Eif4ebp2. Database searching by miRDB and TargetScan predicted that Fli1 and Hs3st5 are the targets of miR-448-3p, and Eif4ebp2 is the target of miR-361-5p. miRNA/mRNA sequencing and qRT-PCR results in blood showed the increased expression of miR-6967-3p and the decreased expression of its target S1pr5. The interactions of these miRNAs and mRNAs may be related to the chronic low-dose-rate radiation-induced persistent DNA damage. Full article

Children with cancer previously treated with radiotherapy face the likelihood of side effects that can be debilitating or fatal. This study aimed to assess the long-term effect of medulloblastoma radiotherapy on the DNA double-strand break (DSB) repair capability of primary fibroblasts derived from lung biopsies of previously irradiated young sheep. This study included biopsies from three control and five irradiated sheep. The treated sheep had previously received spinal radiotherapy at a total dose of 28 Gy, which is equivalent to pediatric medulloblastoma treatment. Lung biopsies were taken 4 years post-irradiation from high-dose (HD, >18 Gy) and low-dose (LD, <2 Gy) regions. Fifteen cell lines were extracted (six control, four LD and five HD). The cells were irradiated, and DNA DSB repair was analyzed by immunofluorescence. Clonogenic, trypan blue and micronuclei assays were performed. Both the HD and LD cell lines had a significantly higher number of residual γH2AX foci 24 h and a significant decrease in pATM activity post-irradiation compared to the control. There was no statistically significant difference in the clonogenic assay, trypan blue and micronuclei results. Our study showed that a previous irradiation can impair the DNA DSB repair mechanism of ovine lung fibroblasts. Full article

In this study, Poly(vinyl alcohol)/cellulose nanofiber (PVA/CNF) hydrogels have been successfully prepared using γ-ray irradiation, annealing, and rehydration processes. In addition, the effects of CNF content and annealing methods on the hydrogel properties, including gel fraction, micromorphology, crystallinity, swelling behavior, and tensile and friction properties, are investigated. Consequently, the results show that at an absorbed dose of 30 kGy, the increase in CNF content increases the gel fraction, tensile strength, and elongation at break of irradiated PVA/CNF hydrogels, but decreases the water absorption. In addition, the cross-linking density of the PVA/CNF hydrogels is significantly increased at an annealing temperature of 80 °C, which leads to the transition of the cross-sectional micromorphology from porous networks to smooth planes. For the PVA/CNF hydrogel with a CNF content of 0.6%, the crystallinity increases from 19.9% to 25.8% after tensile annealing of 30% compared to the original composite hydrogel. The tensile strength is substantially increased from 65.5 kPa to 21.2 MPa, and the modulus of elasticity reaches 4.2 MPa. Furthermore, it shows an extremely low coefficient of friction (0.075), which suggests that it has the potential to be applied as a material for artificial joint cartilage. Full article

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 (Q_β) in PBMCs after mixed α/β-irradiation (50% ²²³Ra & 50% ¹⁷⁷Lu: Q_β = 0.23 ± 0.10) was significantly elevated relative to pure β-irradiation (50 mGy: Q_{β, 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. Full article