Post Irradiation Research Articles

Mitigating the skin phototoxicity of sonodynamic therapy via singlet oxygen-consuming metal-organic frameworks

Sonodynamic anti-cancer therapy relies on the highly active singlet oxygen to induce potent cell death. However, the non-specific biodistribution of sonosensitizers post systemic administration results in a significant accumulation in the skin, and hence the daylight-induced phototoxicity. Here, we report a smart metal-organic framework-based nanocarrier with titanium dioxide (TiO2) as the sonosensitizer for reduced phototoxicity in the skin. The organic ligand bears the imidazole moiety that can facilely consume singlet oxygen in the skin without compromising the anti-cancer efficacy. The reaction between imidazole moiety and singlet oxygen was confirmed by the density functional theory (DFT). Upon light irradiation, the nanocarrier can significantly reduce the phototoxicity post light irradiation in a range of normal cells in vitro and in a mouse model in vivo. Meanwhile, the ligand contains a disulfide moiety that can deplete glutathione and orchestrate the singlet oxygen-induced toxicity in the CT-26 colon cancer cells. As a result, the nanocarrier showed superior in vivo antitumor efficacy in a CT-26 tumor-bearing mice model, leading to significant suppression of tumor growth and improved animal survival rates. The current work provides a tailored nanoscale particle engineering approach to simultaneously minimize phototoxicity in the skin and sensitize sonodynamic anti-cancer therapy.

Persistence luminescence and thermoluminescence of 260 nm UVC irradiated mixed-phase (BaAl2O4 - BaAl12O19) barium aluminate

Persistence luminescence (PerL) and thermoluminescence (TL) of BaAl2O4 - BaAl12O19 mixed phase compound under 260 nm UVC irradiation are studied. The sample shows PerL for more than 1 hour post irradiation. TL glow curves of the sample recorded at 1 oC/s following irradiation to UVC radiation shows a composite glow peak between 30 and 230 oC. The TL intensity is found to be affected by thermal quenching. The activation energy for thermal quenching is estimated to be W=0.85±0.12 eV. A Tm-Tstop analysis reveals that the TL glow peak is composed of multiple first order components. The activation energy associated with the electron traps are found to vary from 0.66 to 1.70 eV. The density of traps is high between 0.60 and 1.20 eV. Due to presence of continuous distribution of electron traps, there is an excellent scope of developing colour tuneable persistence luminescence phosphor using mixed phase barium aluminate.

Linear energy transfer dependent variation in viability and proliferation along the Bragg peak curve in sarcoma and normal tissue cells

Objective.The energy deposition of photons and protons differs. It depends on the position in the proton Bragg peak (BP) and the linear energy transfer (LET) leading to a variable relative biological effectiveness (RBE). Here, we investigate LET dependent alterations on metabolic viability and proliferation of sarcoma and endothelium cell lines following proton irradiation in comparison to photon exposure.Approach.Using a multi-step range shifter, each column of a 96-well plate was positioned in a different depth along four BP curves with increasing intensities. The high-throughput experimental setup covers dose, LET, and RBE changes seen in a treatment field. Photon irradiation was performed to calculate the RBE along the BP curve. Two biological information out of one experiment were extracted allowing a correlation between metabolic viability and proliferation of the cells.Main results.The metabolic viability and cellular proliferation were column-wise altered showing a depth-dose profile. Endothelium cell viability recovers within 96 h post BP irradiation while sarcoma cell viability remains reduced. Highest RBE values were observed at the BP distal fall-off regarding proliferation of the sarcoma and endothelial cells.Significance.The high-throughput experimental setup introduced here (I) covers dose, LET, and RBE changes seen in a treatment field, (II) measures short-term effects within 48 h to 96 h post irradiation, and (III) can additionally be transferred to various cell types without time consuming experimental adaptations. Traditionally, RBE values are calculated from clonogenic cell survival. Measured RBE profiles strongly depend on physical characteristics such as dose and LET and biological characteristics for example cell type and time point. Metabolic viability and proliferation proofed to be in a similar effect range compared to clonogenic survival results. Based on limited data of combined irradiation with doxorubicin, future experiments will test combined treatment with systemic therapies applied in clinics e.g. cyclin-dependent inhibitors.

Space-Like Irradiation Exacerbated Cognitive Deficits and Amyloid Pathology in CRND8 Mouse Model of Alzheimer's Disease.

Space radiation was linked to neurological damage and behavioral deficits which raised concerns of increased degenerative risk on the brain and development of Alzheimer's disease following space travel. In this study, we investigated the effects of irradiation by 56Fe and 28Si in CRND8 mice, an Alzheimer's disease mouse model. Six-month-old CRND8 mice were exposed to whole body irradiation by 56Fe and 28Si at 0.5 Gy and 2 Gy doses. Behavior tests were administered 1-month to 3-months post-irradiation. Amyloid deposition and other pathological changes were analyzed 3-months and/or 6-months post-irradiation. The Novel Object Recognition test showed some decline in 8-month-old mice compared to non-irradiated CRND8 mice. Male mice also showed a loss of freezing behavior in the fear conditioning contextual test following irradiation. Golgi staining revealed a loss of spines in hippocampal neurons after irradiation. Total amyloid immunohistochemistry showed a robust increase in 3-months post-irradiation 56Fe groups which became normalized to non-irradiated group by 6-months post-irradiation. However, 2 Gy 28Si caused a trend towards increased plaque load at 3-months post-irradiation which became significant at 6-months post irradiation only in male CRND8 mice. While 0.5 Gy Fe did not induce obvious changes in the total number of iba-1 positive microglia, more hippocampal microglia were found to express PCNA after 0.5 Gy Fe treatment, suggesting potential involvement of microglial dysfunction. Overall, our study provides new evidence of gender-specific and ion-dependent effects of space radiation on cognition and amyloid pathology in AD models.

Early and Late Effects of Low-Dose X-ray Exposure in Human Fibroblasts: DNA Repair Foci, Proliferation, Autophagy, and Senescence.

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.

Modulatory effect of the fruit rind extract of Garcinia indica Choisy against gamma radiation induced damage in human peripheral blood lymphocytes: a preliminary study

Purpose Nowadays people are exposed to radiation due to various reasons, including natural, diagnostic, occupational or accidental exposure. High level of exposure to ionizing radiation can be fatal to human body. Synthetic drugs used to prevent radiation-induced damage are toxic in nature. Recently, Herbal drugs are being screened as an alternative due to their mechanism of action. Garcinia indica (G. indica) is one of the traditional medicinal plant which contains phytochemicals having several medicinal properties. Materials and methods In this study, G. indica extract was observed for its modulatory effect against 3 Gray (Gy) gamma radiation-induced damages in human peripheral blood lymphocytes. Various concentrations of G. indica extract ranging from 1 to 25 µg/mL was added to the blood post irradiation at 0 hr. Chromosomal aberration (CA) and Cytochalasin B blocked Micronuclei Cytome (CBMN) Assay were performed as per standard procedure. Results Radiomodulatory effect of Garcinia indica fruit rind extract (GIFRE) on CA and MN formation was observed in this study. Treatment of GIFRE did not affect the mitotic index. Positive inhibition percentages for dicentrics, total chromosomal aberrations and micronuclei were observed except for one instance. Conclusion Owing to the various properties of Garcinia extracts, it makes it a potential candidate to be tested for its radiomodulatory effect. Based on the results observed in this preliminary study, it could act as a radiomodulatory agent. Radiomodulatory effect of GIFRE could possibly serve it as a potential herbal medicinal alternative to current drugs. However, results of this study need to be validated on larger sample size.

Long-term toxicity and efficacy of FLASH radiotherapy in dogs with superficial malignant tumors.

FLASH radiotherapy (RT) has emerged as a promising modality, demonstrating both a normal tissue sparing effect and anticancer efficacy. We have previously reported on the safety and efficacy of single fraction FLASH RT in the treatment of oral tumors in canine cancer patients, showing tumor response but also a risk of radiation-induced severe late adverse effects (osteoradionecrosis) for doses ≥35 Gy. Accordingly, the objective in this study was to investigate if single fraction high dose FLASH RT is safe for treating non-oral tumors. Privately-owned dogs with superficial tumors or microscopic residual disease were included. Treatment was generally delivered as a single fraction of 15-35 Gy 10 MeV electron FLASH RT, although two dogs were re-irradiated at a later timepoint. Follow-up visits were conducted up to 12 months post-treatment to evaluate treatment efficiency and adverse effects. Fourteen dogs with 16 tumors were included, of which nine tumors were treated for gross disease whilst seven tumors were treated post-surgery for microscopic residual disease. Four treatment sites treated with 35 Gy had ulceration post irradiation, which was graded as severe adverse effect. Only mild adverse effects were observed for the remaining treatment sites. None of the patients with microscopic disease experienced recurrence (0/7), and all patients with macroscopic disease showed either a complete (5/9) or a partial response (4/9). Five dogs were euthanized due to clinical disease progression. Our study demonstrates that single fraction high dose FLASH RT is generally safe, with few severe adverse effects, particularly in areas less susceptible to radiation-induced damage. In addition, our study indicates that FLASH has anti-tumor efficacy in a clinical setting. No osteoradionecrosis was observed in this study, although other types of high-grade adverse effects including ulcer-formations were observed for the highest delivered dose (35 Gy). Overall, we conclude that osteoradionecrosis following single fraction, high dose FLASH does not appear to be a general problem for non-oral tumor locations. Also, as has been shown previously for oral tumors, 30 Gy appeared to be the maximum safe dose to deliver with single fraction FLASH RT.

Monte Carlo simulations of microdosimetry and radiolytic species production at long time post proton irradiation using GATE and Geant4-DNA.

Radiobiological effectiveness of radiation in cancer treatment can be studied at different scales (molecular till organ scale) and different time post irradiation. The production of free radicals and reactive oxygen species during water radiolysis is particularly relevant to understand the fundamental mechanisms playing a role in observed biological outcomes. The development and validation of Monte Carlo tools integrating the simulation of physical, physico-chemical and chemical stages after radiation is very important to maintain with experiments. Therefore, in this study, we propose to validate a new Geant4-DNA chemistry module through the simulation of water radiolysis and Fricke dosimetry experiments on a proton preclinical beam line. In this study, we used the GATE Monte Carlo simulation platform (version 9.3) to simulate a 67.5 MeV proton beam produced with the ARRONAX isochronous cyclotron (IBA Cyclone 70XP) at conventional dose rate (0.2Gy/s) to simulate the irradiation of ultra-pure liquid water samples and Fricke dosimeter. We compared the depth dose profile with measurements performed with a plane parallel Advanced PTW 34045 Markus ionization chamber. Then, a new Geant4-DNA chemistry application proposed from Geant4 version 11.2 has been used to assess the evolution of , , , , , , and reactive species along time until 1-h post-irradiation. In particular, the effect of oxygen and pH has been investigated through comparisons with experimental measurements of radiolytic yields for and Fe3+. GATE simulations reproduced, within 4%, the depth dose profile in liquid water. With Geant4-DNA, we were able to reproduce experimental radiolytic yields 1-h post-irradiation in aerated and deaerated conditions, showing the impact of small changes in oxygen concentrations on species evolution along time. For the Fricke dosimeter, simulated G(Fe3+) is 15.97±0.2 molecules/100eV which is 11% higher than the measured value (14.4±04 molecules/100 eV). These results aim to be consolidated by new comparisons involving other radiolytic species, such as or to further study the mechanisms underlying the FLASH effect observed at ultra-high dose rates (UHDR).

Albumin nanoparticle electrostatically loaded with highly anionic Gd-thiacalixarene complex for MRI-guided neutron capture therapy

As a neutron capture therapy (NCT) agent, 157Gd garners significant attention due to the largest neutron capture cross section, emission of γ rays and Auger electrons, and facilitation of magnetic resonance imaging-guided NCT. Owing to its high kinetic stability, 1H relaxivity, and facile conjugation to albumin via electrostatic interactions, the negatively charged Gd3TCAS2 complex {TCAS = thiacalix[4]arene-p-tetrasulfonate (TCAS)} was incorporated into albumin nanoparticles (ANPs) in various configurations, including shell, core, and core-shell types, contingent on the positioning of Gd3TCAS2 within the ANP. The characteristics of the ANPs optimized with respect to loading capacity (LC) were explored, all of which demonstrated particle sizes suitable for passive delivery. The LC of Gd3TCAS2 per ANP increased in the following order: shell (1.1 %) < core (1.4 %) < core-shell (8.1 %). The leakage of Gd3TCAS2 after 7 d of storage was approximately 2 % for all ANPs, indicating stable Gd3TCAS2 loading. The 1H relaxivity (e.g., core-shell: r1 = 10.7 mM–1s–1) surpassed that of the Gd3TCAS2 complex alone (3.15 mM–1s–1). The luminescence emanating from Tb in MCF-7 cells co-cultured with Tb3TCAS2-loaded ANPs corroborated this cellular uptake. Gd uptake into MCF-7 cells via Gd3TCAS2-loaded ANPs was most pronounced for core-shell ANP at 1.33 ± 0.06 nmol/106 cells. The cytotoxicity of Gd3TCAS2-loaded ANPs was mitigated compared to free Gd3TCAS2 (CC50 = 52 µM), with shell and core-shell ANPs demonstrating nearly 100 % cell survival even at 50 µM. Cell viability post thermal neutron irradiation revealed the highest NCT efficacy for free Gd3TCAS2, attributed to its elevated cellular uptake (15.71 ± 0.57 nmol/106 cells). Core-shell ANP also exhibited a notable reduction in cell viability relative to the control, validating their potential as a promising GdNCT agent.

Postmortem pathologic findings in dogs that underwent total body irradiation and hematopoietic cell transplant: A case series of five dogs with B-cell multicentric lymphoma.

Alternative therapies that can help achieve complete remission in dogs with lymphoma include total body irradiation and hematopoietic cell transplant, though there are few reports describing successes and pathologic sequelae of these procedures. During a 10-year period, 94 dogs with multicentric lymphoma received a hematopoietic cell transplant following total body irradiation at North Carolina State University College of Veterinary Medicine. Seven of these 94 dogs (7%) died prior to discharge, five (5%) of which presented for postmortem examination. Of these dogs, four received an autologous hematopoietic cell transplant, while one received a haploidentical allogeneic hematopoietic cell transplant. All five dogs had bone marrow depletion with all hematopoietic lines affected. Three had systemic candidiasis, while two had bacterial infections. To the authors' knowledge, this is the first report to document pathologic findings and development of systemic mycoses in dogs post total-body irradiation therapy and hematopoietic cell transplant.

L. plantarum and L. casei synergistically mitigate Gastro-Intestinal Acute Radiation Syndrome (GI-ARS)

Introduction: Incidental or accidental acute exposure to ionizing radiation causes radiation toxicity, for which there are no known medical countermeasures (MCMs). Ionizing radiation alters host gut epithelium as well as the gut microbiome. We sought to investigate if radiation induced gut dysbiosis occurred as a result of depletion of gut-protective bacteria, and if probiotic supplementation of such bacteria could help mitigate GI-ARS post ionizing radiation exposure. Methods: Adult C57BL/6 mice were subjected to total body irradiation, and a defined concentration of probiotics (either individually or combined) were given 24 h after radiation exposure. Mice were sacrificed 24 hours post treatment (i.e., 48 h post irradiation). Vascular-to-luminal flux of FITC-inulin was measured to evaluate intestinal mucosal permeability and endotoxemia by measuring plasma lipopolysaccharide. Gut microbiota was analyzed by 16S rRNA sequencing. Intestinal epithelial junctions were analyzed by immunofluorescence confocal microscopy and mucosal inflammatory response by RT-PCR for cytokine expression. Systemic inflammation was evaluated by ELISA for plasma cytokines. Results and conclusion: Our data show that radiation altered the taxonomic composition of the microbiota compared to age-matched sham treated mice. Shannon index analysis showed a significant decrease in α-diversity in irradiated mice. Bray-Curtis analysis indicated significant differences in microbiota composition between Sham and IR groups. E. coli abundance was increased whereas Lactobacillus abundance was decreased, particularly L. plantarum and L. casei. Probiotic supplementation with individual Lactobacillus species each mitigated radiation induced intestinal barrier dysfunction, gut specific as well as systemic inflammatory cytokine expression and endotoxemia. Our preliminary data further indicates that L. plantarum affects Epidermal Growth Factor Receptor (EGFR)-mediated signaling whereas L. casei was EGFR-independent. Interestingly, combined supplementation in a 1:1 ratio further enhanced recovery compared to adding the individual effects. Individual supplementation of L. plantarum and L. casei to irradiated mice reduced intestinal (ileal) permeability by 2-fold and 3-fold respectively, whereas combined supplementation reduced ileal permeability almost 8-fold compared to irradiated but untreated mice. This data indicates that L. plantarum and L. casei mitigate GI-ARS by distinct cellular mechanisms. Furthermore, data show that a mixture of these probiotic species is more effective in radio-mitigation than individually. Further mechanistic analysis will be required to identify cross-talking targets between mechanisms of these probiotics and synergistic radio-mitigation. In conclusion, Lactobacillus species are potential MCMs for the treatment of GI-ARS. Funding acknowledgements: NIH/NIAID, UO1-AI170019, UO1-AI172991. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Fission accelerated steady-state post irradiation examinations - Part II

The Advanced Fuels Campaign's Fission Accelerated Steady State Testing (FAST) approach at Idaho National Laboratory creates a benchmark for evaluating accelerated irradiation via control rodlets and advanced metal fuel alloys for sodium-cooled fast reactors (SFRs). FAST experiments have been developed to generate prototypic temperature conditions during steady state irradiations of scaled geometric fuel pins. This approach helps to attain higher burn ups at a much faster rate than previous irradiation tests. For this study, the results from profilometry, fission gas release, and metallography of a FAST experiment are presented. Profilometry determined 0 % effective strain in the rodlets. The fission gas release fraction was measured from puncture/collection analysis. Constituent redistribution was observed in two specimens despite the peak fuel temperatures being below the normal ranges in which redistribution is expected. Metallography of the two higher temperature specimens showed typical swelling with the solid pin closing the fuel-cladding gap and the annular specimen having a fully closed annulus. Additionally, metallography indicated no swelling, no redistribution, and a homogenous microstructure for specimens with lower irradiation temperature. Post irradiation examination of FAST rodlets generally showed the expected representative behavior of metallic fuels within SFRs.

Quinazoline sulfonamide derivatives targeting MicroRNA-34a/MDM4/p53 apoptotic axis with radiosensitizing activity.

Aim: New quinazoline benzenesulfonamide hybrids 4a-n were synthesized to determine their cytotoxicity and effect on the miR-34a/MDM4/p53 apoptotic pathway. Materials & methods: Cytotoxicity against hepatic, breast, lung and colon cancer cell lines was estimated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: Compound 4d was the most potent against HepG2 and MCF-7 cancer cells, with potential apoptotic activity verified by a significant upregulation of miR-34a and p53 gene expressions. The apoptotic effect of 4d was further investigated and showed downregulation of miR-21, VEGF, STAT3 and MDM4 gene expression. Conclusion: The anticancer and apoptotic activities of 4d were enhanced post irradiation by a single dose of 8Gy γ-radiation. Docking analysis demonstrated a valuable affinity of 4d toward VEGFR2 and MDM4 active sites.

Proteomic and phosphoproteomic characterization of cardiovascular tissues after long term exposure to simulated space radiation.

Introduction: It may take decades to develop cardiovascular dysfunction following exposure to high doses of ionizing radiation from medical therapy or from nuclear accidents. Since astronauts may be exposed continually to a complex space radiation environment unlike that experienced on Earth, it is unresolved whether there is a risk to cardiovascular health during long-term space exploration missions. Previously, we have described that mice exposed to a single dose of simplified Galactic Cosmic Ray (GCR5-ion) develop cardiovascular dysfunction by 12months post-radiation. Methods: To investigate the biological basis of this dysfunction, here we performed a quantitative mass spectrometry-based proteomics analysis of heart tissue (proteome and phosphoproteome) and plasma (proteome only) from these mice at 8months post-radiation. Results: Differentially expressed proteins (DEPs) for irradiated versus sham irradiated samples (fold-change ≥1.2 and an adjusted p-value of ≤0.05) were identified for each proteomics data set. For the heart proteome, there were 87 significant DEPs (11 upregulated and 76 downregulated); for the heart phosphoproteome, there were 60 significant differentially phosphorylated peptides (17 upregulated and 43 downregulated); and for the plasma proteome, there was only one upregulated protein. A Gene Set Enrichment Analysis (GSEA) technique that assesses canonical pathways from BIOCARTA, KEGG, PID, REACTOME, and WikiPathways revealed significant perturbation in pathways in each data set. For the heart proteome, 166 pathways were significantly altered (36 upregulated and 130 downregulated); for the plasma proteome, there were 73 pathways significantly altered (25 upregulated and 48 downregulated); and for the phosphoproteome, there were 223 pathways significantly affected at 0.1 adjusted p-value cutoff. Pathways related to inflammation were the most highly perturbed in the heart and plasma. In line with sustained inflammation, neutrophil extracellular traps (NETs) were demonstrated to be increased in GCR5-ion irradiated hearts at 12-month post irradiation. NETs play a fundamental role in combating bacterial pathogens, modulating inflammatory responses, inflicting damage on healthy tissues, and escalating vascular thrombosis. Discussion: These findings suggest that a single exposure to GCR5-ion results in long-lasting changes in the proteome and that these proteomic changes can potentiate acute and chronic health issues for astronauts, such as what we have previously described with late cardiac dysfunction in these mice.

Abstract 6036: Flash proton radiotherapy mitigates radiation-induced salivary gland dysfunction and oral mucositis in mice

Abstract Background- Recent studies have reported that ultra-high dose rate “FLASH” Proton radiation therapy (F-PRT) decreases normal tissue toxicity while maintaining tumor-controlling efficacy compared to Standard Proton RT (S-PRT), that are used for patient treatments. However, although highly efficacious in eliminating tumors, damage to the otherwise healthy salivary glands and oral mucosa is often unavoidable in patients with head and neck cancer, leaving patients with lifelong xerostomia and other comorbidities. Aim- In this study, we aimed to investigate the effect of F-PRT on radiation-induced oral mucositis and salivary gland dysfunction and in controlling orthotopic tumor growth. Methods- The head and neck area of C57Bl/6 mice was irradiated with a single dose of 16 Gy or a fractionated dose of 8 Gy x 3 of F-PRT (128Gy/s) or S-PRT (0.95 Gy/s). Oral mucositis was analyzed by histopathological examination. Radiation-induced xerostomia was studied by measuring the saliva flow rate of mice. To examine the ability of F-PRT to control orthotopic head and neck tumors, tongue tumors were generated in mice and then irradiated with F-PRT/S-PRT. Results- Following irradiation with a single dose or a fractionated dose, saliva flow was reduced by both treatments. However, the F-PRT-treated mice showed a significant improvement in salivary flow at 14 days (p&amp;lt;0.05) and 28 days (p&amp;lt;0.005) post irradiation. Expression of AQP5 was found to be significantly down-regulated at 2, 5, 10, and 14 days post irradiation with S-PRT. However, mice irradiated with F-PRT showed a significant restoration of the AQP5 expression post-RT. Oral mucositis started to appear on day 14, which showed more severity on day 28 post-irradiation with S-PRT. Histopathological analysis showed the presence of lingual gland atrophy only in the tongue of mice treated with S-PRT 28 and 60 days post-irradiation. F-PRT ameliorates radiation-induced jawbone loss compared to S-PRT as observed in mice irradiated either with a single dose or in a fractionated regime. The surviving fraction of F-PRT-treated mice with orthotopic tongue tumors was significantly ameliorated compared to S-PRT-treated mice. Conclusion- This study demonstrates that F-PRT minimizes radiation-induced normal tissue toxicity after irradiation in mice’s head and neck region. Moreover, the ability of F-PRT to control orthotopic head and neck tumors further determines the efficacy of this modality for clinical applications. Citation Format: Priyanka Chowdhury, Anastasia Velalopoulou, Ioannis Verginadis, George Morcos, Michele Kim, James Metz, Lei Dong, Alexander Lin, Constantinos Koumenis. Flash proton radiotherapy mitigates radiation-induced salivary gland dysfunction and oral mucositis in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6036.

Neutron irradiation effect on superconductivity of Nb3Sn wire - 50 Hz data acquisition system -

A research facility for neutron irradiation effect on superconducting materials has been installed at Oarai center in Tohoku University in 2012 as part of a post irradiation experiment. It consists of a 15.5 T superconducting magnet, a variable temperature insert and a data acquisition and control system. Since the sample holder is cooled by thermal conduction with G-M refrigeration, there is a small temperature difference between positive and negative electrodes and the sample temperature rises during the critical current test due to joule heating. To evaluate the temperature rise precisely, a new data acquisition system with a sampling rate of 50 Hz has been installed. By measuring the temperatures of both electrodes and the voltage at the center of the sample, the temperature of the sample was estimated and the measured critical current (IC) was converted to the current at 4.2 K with a critical surface equation. The comparison of IC at different conditions including neutron irradiated samples was implemented and the neutron irradiation effect on superconductivity of Nb3Sn wire is discussed based on the 4.2 K superconductivity. This paper will describe the outline of the new data acquisition system and some results of neutron irradiated Nb3Sn wires.

Effect of Radiotherapy on Activating the Pyroptotic Cell Death Pathway in Breast Cancer Patients: The Role of Serum GSDMD-CT, NLRP3 and IL-18.

Breast cancer (BC) is the most common form of cancer among women and the second leading cause of cancer-related death worldwide. Several malignancies can be successfully treated with radiation (RT), although radioresistance is still a major contributor to radiotherapy failure. Ionizing radiation (IR) induces pyroptosis in cancer cells. Pyroptosis is a designed method of death connected to routine immunity and directly related to the body ROS content. Objective for the study: The aim of this work was to investigate the role of serum GSDMD-CT, nucleotide-binding domain and leucine-rich-repeat-containing family pyrin 3 (NLRP3) and IL-18 as predictors of pyroptotic cell death mechanism induced by radiotherapy in breast cancer patients. The 70 female participants in this study were divided into two groups: Group (I): 40 breast cancer patients treated with radiotherapy. Group (II): a control group of 30 healthy volunteers with similar ages and sex. Patients with breast cancer received radiation, with a dose of 44 Gray administered over the course of 16 days in five daily fractions of 2.75 Gray each. Two blood samples were taken from breast cancer patients: one before radiotherapy and the other after radiotherapy. While one blood sample was taken from healthy controls. The levels of the circulating pyroptosis biomarkers IL-18, NLRP3, and GSDMD-CT were measured using the ELISA method. Our results showed that, there was a significant increase in serum pyroptosis markers GSDMD-CT, NLRP3 and IL-18 in BC Patients after RT when compared to before radiotherapy. Radiotherapy induced pyroptosis in breast cancer patients as a new cell death mechanism. GSDMD-CT, NLRP3 and IL-18 are biomarkers of pyroptosis that significantly increased post irradiation highlighting enhanced ROS and pyroptosis induction.

Unraveling the effect of 600 keV carbon ion irradiation on the structural and magnetic properties of ZnO thin film

600 keV 12C+ carbon ions have been irradiated upon 800 nm thin ZnO film. The thin ZnO films have been grown by pulsed laser deposition technique upon SiO2/Si substrate. The glancing incidence X-ray diffraction study exhibits the hexagonal wurtzite crystal structure of ZnO, having space group P63mc. Systematic X-ray diffraction analysis of both unirradiated and irradiated samples, reveals that the strain decreases in the sample post irradiation. Room temperature magnetization studies have been performed using SQUID-VSM. As the 600 keV carbon ion fluence is varied, an onset of ferromagnetic ordering in the ZnO thin film is observed. The maximum average magnetic moment induced by each carbon ion is found to be about 6.71 μB. X-ray photoelectron spectroscopy has been utilized to analyze the oxidation state of the C/O/Zn, which also rules out the presence of any transition metal elements in carbon ions irradiated ZnO thin film samples. The chemical and structural analysis of the samples have been examined by Raman spectroscopy. It reveals a red shift in A1 (LO) mode, which confirms the presence of tensile strain in the sample post irradiation. These experimental results, clearly indicate that oxygen vacancies and strain in the film trigger the onset of ferromagnetism in the ZnO thin film system.

Phenotypic and transcriptional changes in lens epithelial cells following acute and fractionated ionizing radiation exposure

Purpose Exposure to ionizing radiation is one of the known risk factors for the development of lens opacities. It is believed that radiation interactions with lens epithelial cells (LEC) are the underlying cause of cataract development, however, the exact mechanisms have yet to be identified. The aim of this study was to investigate how different radiation dose and fractionation impact normal LEC function. Materials and methods A human derived LEC cell line (HLE-B3) was exposed to a single acute x-ray dose (0.25 Gy) and 6 fractionated doses (total dose of 0.05, 0.1, 0.25, 0.5, 1, and 2 Gy divided over 5 equal fractions). LEC were examined for proliferation using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and migration using a Boyden chamber assay at various time points (0.25, 0.5, 1, 2, 4, 7, 9, 11, and 14 d) post-irradiation. Transcriptomic analysis through RNA sequencing was also performed to identify differentially expressed genes and regulatory networks in cells following 4 different acute exposures and 1 fractionated exposure. Results Exposure to an acute dose of 0.25 Gy significantly increased proliferation and migration rates, peaking at 7 d post irradiation (20% and 240% greater than controls, respectively), before returning to baseline levels by day 14. Fractionated exposures had minimal effects up to a dose of 0.5 Gy, but significantly reduced proliferation and migration after 1 and 2 Gy by up to 50%. The largest transcriptional response occurred 12 h after an acute 0.25 Gy dose, with 362 genes up-regulated and 288 genes down-regulated. A unique panel of differentially expressed genes was observed between moderate versus high dose exposures, suggesting a dose-dependent transcriptional response in LEC that is more pronounced at lower doses. Gene ontology and upstream regulator analysis identified multiple biological processes and molecular functions implicated in the radiation response, in particular differentiation, motility, receptor/ligand binding, cell signaling and epithelial-mesenchymal cell transition. Conclusions Overall, this research provides novel insights into the dose and fractionation effects on functional changes and transcriptional regulatory networks in LEC, furthering our understanding of the mechanisms behind radiation induced cataracts.

Palmitoyl ascorbic acid glucoside enhanced cell survival with post irradiation treatment

Radiation exposure poses a significant threat to cellular integrity by inducing DNA damage through the generation of free radicals and reactive oxygen species. Ascorbic acid, particularly its derivative Palmitoyl Ascorbic Acid 2-Glucoside (PA2G), has demonstrated remarkable radioprotective properties. While previous research focused on its pre-irradiation application, this study explores the post-irradiation radiomitigation potential of PA2G. Our findings reveal that post-irradiation treatment with PA2G enhances cell survival and accelerates DNA repair processes, particularly the non-homologous end-joining (NHEJ) repair pathway. Notably, PA2G treatment reduces the frequency of lethal chromosomal aberrations and micronuclei formation, indicating its ability to enhance the repair of complex DNA lesions. Furthermore, PA2G is shown to play a role in potentially lethal damage repair (PLDR). These radioprotective effects are specific to NHEJ and ATM pathways, as cells deficient in these mechanisms do not benefit from PA2G treatment. This study highlights PA2G as a versatile radioprotector, both pre- and post-irradiation, with significant potential for applications in radiation therapy and protection, offering new insights into its mechanism of action. Further research is required to elucidate the precise molecular mechanisms underlying PA2G's radiomitigation effects and its potential clinical applications.