Radiation research最新文献

{"title":"Mechanisms of Radiation-induced Brain Injury in Mice Based on Bioinformatics Analysis.","authors":"Peiquan Liu, Min Fu, Dong Liu, Tengfei Chao, Jiaxuan Zhang","doi":"10.1667/RADE-24-00204.1","DOIUrl":"10.1667/RADE-24-00204.1","url":null,"abstract":"<p><p>Radiation therapy is a crucial adjunct treatment for head and neck tumors, as well as primary or metastatic brain tumors. Radiation-induced brain injury is one of the most severe complications, postirradiation, in patients with head and neck tumors, and significantly impacts their quality of life. Currently, there are no effective treatments for radiation-induced brain injury, making the study of radiation-induced molecular mechanisms and the identification of early damage biomarkers critical for the early diagnosis and treatment of such injuries. In this study, twelve male C57 mice aged 6-8 weeks were randomly divided into a control group, a 15 Gy irradiation group, and a 30 Gy irradiation group. Mice were exposed to 6 MV X rays. The control group underwent the same anesthesia procedure as the irradiated groups but did not receive radiation. General health and weight changes were monitored and recorded. Four months postirradiation, mice were subjected to intracranial magnetic resonance imaging [T2-weighted imaging (T2WI)], open field test (OFT), novel object recognition (NOR), followed by a collection of brain tissues for immunofluorescence, SA-β-gal staining, and transcriptomic and metabolomic analyses. Compared to the control group, the 15 Gy and 30 Gy irradiated mice showed reduced activity and weight loss. The irradiated mice exhibited impaired recognition memory in the NOR test and decreased body weight, but radiation had no significant effect on weight or performance in the OFT. Electron microscopy reveals significant demyelination of mouse cortex after irradiation, and MRI T2-weighted imaging demonstrated varying degrees of brain atrophy and ventricular enlargement in irradiated mice compared to the control group. Immunofluorescence staining showed a significant increase in astrocytes and microglia activated after irradiation. SA-β-gal staining revealed significant increases in the numbers of β-gal+ cells in irradiated mice compared to those in untreated control mice. Bioinformatics analysis identified enriched pathways primarily related to lipid metabolism and neuroinflammatory responses; associated metabolites and genes were variously upregulated or downregulated. The findings suggest that radiation-induced brain injury involves complex biological processes, with lipid metabolism disorders and neuroinflammation being the predominant pathological changes observed. Further studies on these metabolic pathways and genes could enhance our understanding of the pathogenic mechanisms underlying radiation-induced brain injury and identify potential therapeutic targets.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"321-332"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lethality Assessments for Acutely Irradiated Cynomolgus Macaques Under Subject-based Care.","authors":"Issa Melendez-Miranda, Oluseyi O Fatanmi, Stephen Y Wise, Sarah A Petrus, Alana D Carpenter, Cara Olsen, Artur A Serebrenik, Luis A Lugo-Roman, Thomas M Seed, Michael D Kaytor, Vijay K Singh","doi":"10.1667/RADE-24-00223.1","DOIUrl":"10.1667/RADE-24-00223.1","url":null,"abstract":"<p><p>Well-characterized animal models of acute radiation syndrome are needed for the development of radiation medical countermeasures to mitigate injury due to acute exposure to high doses of total- or partial-body radiation. Such animal models must reveal a radiation dose- and time-dependent relationship, pathogenesis of injury, and clinical presentation similar to humans. The focus of this study was to investigate clinical responses, principally lethality patterns, of cynomolgus macaques acutely exposed to relatively high doses of total-body radiation. Such investigations are currently relevant due to the limited availability of rhesus macaques, the dominant and preferred macaque subspecies, due to limited supply and their use in other high-priority areas. In this study employing cynomolgus macaques, a preliminary dose-response relationship was determined using three different radiation doses (4.7, 5.8 and 6.5 Gy, n = 24, n = 8/radiation dose) at a dose rate of 0.6 Gy/min. Animals were provided subject-based supportive care excluding blood products and were monitored for 60 days postirradiation for survival, which was the primary endpoint and the secondary endpoint was hematopoietic recovery. The lethality curve suggested LD30/60, LD50/60, and LD70/60 values as 4.8, 5.3, and 5.8 Gy, respectively. The initial results of this study are deemed critical for future efficacy assessments of newly developed medical countermeasures for acute radiation injuries by making use of an alternative subspecies of macaques, namely cynomolgus macaques (Macaca fascicularis).</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"304-320"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Combined Therapy of Pegylated G-CSF with Ciprofloxacin Mitigates Damage Induced by Lethal Ionizing Radiation to the Bone Marrow, Spleen, and Ileum by Increasing AKT Activation but Decreasing IL-18, C3, and miR-34a.","authors":"Juliann G Kiang, Georgetta Cannon, Min Zhai, Matthew G Olson, Akeylah K Woods, Katherine S Cleveland, Hengying Ellery, Feng Xu, Mang Xiao","doi":"10.1667/RADE-24-00266.1","DOIUrl":"10.1667/RADE-24-00266.1","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Ciprofloxacin (CIP) was found to enhance pegylated G-CSF therapy (PEG, Neulasta®)-induced survival from 30% to 85% after ionizing radiation exposure. This combined therapy significantly mitigated radiation-induced brain hemorrhage through its capability to improve platelet recovery. This study tested whether this combined treatment also mitigated gastrointestinal damage from radiation. B6D2F1 female mice were exposed to 60Co γ radiation. CIP was fed daily to mice for up to 14 days. PEG was injected on day 1, and then weekly up to day 14. For the early time point study, blood, femurs, spleen, and ileum were collected on days 2, 4, 9, and 15 postirradiation. Bone marrow cells were counted; spleen weights and splenocyte counts were measured; and ileum histopathology was examined and analyzed. AKT, ERK, JNK, p38, claudin 2, NF-kB, Bax, Bcl-2, and gasdermin D were measured in ileum lysates using Western blotting while miR-34a was measured by reverse transcription followed by real-time-PCR, and citrulline was measured by colorimetric assay. In serum, interleukin-18 (IL-18) was measured by Luminex assay and complement protein 3 (C3) was detected by ELISA. The bacterial DNA load in livers was measured by real-time PCR. Radiation depleted bone marrow cells in femurs beginning day 2 through day 15 postirradiation, which was mitigated by PEG or CIP+PEG on day 9 through day 15 and by CIP on day 15, respectively. Radiation exposure led to decreased spleen weight on day 2 through day 15, while PEG or CIP+PEG significantly mitigated the reduction on day 9 through day 15. Radiation exposure reduced splenocyte counts on day 2 through day 15 postirradiation, but that was mitigated by PEG or CIP+PEG on day 15. Ileum histology showed that radiation decreased villus height on day 2 through day 15; CIP mitigated the reduction on day 15, whereas PEG+CIP mitigated it on day 2 through 15. Villus widths were increased on day 2 through day 15, while PEG+CIP effectively decreased them on day 4 through day 15. Crypt depth was reduced by radiation on day 2, but returned to the baseline on day 4 through 15. CIP or CIP+PEG transiently increased the depth only on day 4. Crypt counts were reduced by radiation on days 2 and 4, but returned to the baseline on days 9 and 15, regardless of individual drugs or combinations. Citrulline data confirmed the villus height recovery. Radiation significantly increased pro-inflammatory cytokine IL-18 on days 4 and 9, which was mitigated by PEG alone or PEG+CIP, but not by CIP alone. Radiation increased C3 on day 9 in ileum and serum. The serum C3 was positively associated with the serum IL-18 levels and negatively correlated with the crypt depth. Radiation-induced decreases in claudin 2 (a tight junction marker) in ileum and increases in bacterial DNA in livers were mitigated by PEG+CIP. Radiation did not reduce NF-kB and its activation but reduced Bcl-2 expression, which was not significantly recovered by any individual drug or combinat","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"341-356"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal High-fat Diet Modulates Radiosensitivity of Hematopoietic Tissue in Male Offspring.","authors":"Takanori Katsube, Masahiro Murakami, Kaoru Tanaka, Takamitsu Morioka, Shizuko Kakinuma, Bing Wang","doi":"10.1667/RADE-24-00163.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00163.1","url":null,"abstract":"<p><p>Obesity is a growing global health concern, and the Western diet characterized by its high-calorie and high-fat content, is widely acknowledged as a major contributor. Obesity is closely linked to the onset of various metabolic syndromes in affected individuals. Furthermore, maternal obesity has been revealed to have persistent effects on the long-term health of offspring, a phenomenon widely recognized as the \"developmental origins of health and disease\" (DOHaD). In this study, we aimed to explore the potential modifying effects of maternal exposure to a high-fat diet (HFD) on the health outcomes of offspring after exposure to ionizing radiation. C57BL/6J female mice were fed either an HFD or a standard diet (STD) immediately after weaning at 3 weeks of age. At 10 weeks of age, they were mated with C3H/He male mice raised on an STD. The resulting pups were nursed by their dams and were subjected to a total body X-ray dose of 3.8 Gy at 7 days after birth. All pups were weaned onto an STD at 4 weeks of age, irrespective of their experimental group. Lifelong observation of these pups demonstrated that maternal exposure to HFD reduced the lifespan of male offspring postirradiation, whereas maternal HFD alone did not significantly impact the lifespan of both male and female offspring. Pathological analysis revealed that the lifespan shortening by maternal HFD after X irradiation was primarily attributed to early deaths associated with depletion of bone marrow cells and thymic lymphoma within 6 months after X irradiation. To the best of our knowledge, this is the first report showcasing the modifying effects of maternal HFD on the radiosensitivity of offspring.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Octamer-Binding Transcription Factor 4 Inhibits HSC Functions via the NF-κB Signaling Pathway After 60Co Irradiation.","authors":"Wenjing Yang, Xiaoe Jin, Chao Chen, Qianqian Zhang, Junyang Wang, Jinjia Liu, Lina Song, Xiaolong Jiang, Yunjian Liu, Weihong Li, Shufang Cui","doi":"10.1667/RADE-24-00258.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00258.1","url":null,"abstract":"<p><p>High doses of radiation can cause irreversible bone marrow hematopoietic damage and even death. No effective strategies have been developed to protect against radiation effects in hematopoietic stem cells (HSCs). A total-body irradiation model was used to determine damage to HSCs. HSCs were sorted for transcriptome sequencing, and gene function analysis showed that Octamer-Binding Transcription Factor 4 (Oct4) increased significantly after irradiation. Oct4 deletion or inhibition of nuclear factor kappa-B (NF-κB) significantly reversed HSC apoptosis, promoted HSC colony formation, reduced cellular DNA damage, and promoted bone marrow regeneration after irradiation. ChIP assays showed that Oct4 binds to the IκB kinase (IKK) promoter region and increases the level of IKK. Overexpression of Oct4 significantly increased the entry of NF-κB into the nucleus after irradiation. NF-κB activators reversed the protective roles of knocking out Oct4. In vivo, the knockout of Oct4 and inhibition of NF-κB significantly improved the survival rate of mice after irradiation. We further found that the expression level of Oct4 decreased significantly in human leukemia cells, while the overexpression of Oct4 significantly increased the level of apoptosis in leukemia cells after irradiation. This study demonstrated a novel role of Oct4 in mediating apoptosis of HSCs after irradiation through the NF-κB pathway, providing an important biomedical strategy for the functional protection of HSCs in bone marrow after irradiation.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidants Ameliorates Ionizing Radiation-Induced Microcephaly in Cerebral Organoid Derived from Human-induced Pluripotent Stem Cells.","authors":"Mikio Shimada, Yoshihisa Matsumoto","doi":"10.1667/RADE-25-00017.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00017.1","url":null,"abstract":"<p><p>Ionizing radiation exposure induces DNA damage and chromosome aberrations through both direct and indirect effect. The indirect effects are primarily mediated by the generation of hydroxyl radicals, a process attributed to radiation. Dimethyl sulfoxide (DMSO) and ascorbic acid (AA) are known as radical scavengers and have radioprotective effects. Radiation therapy is widely employed in the treatment of malignant tumors such as glioblastoma; however, its side effects, including cognitive impairments resulting from damage to healthy neurons, pose significant challenges. To ameliorate these effects, radioprotective reagents have been sought. In this study, we used cerebral organoids derived from human-induced pluripotent stem cells to address the radioprotective effect of radical scavengers, DMSO and AA in brain exposure. Although exposure to radiation for 20-day-old cerebral organoids results in DNA double-strand breaks and apoptosis leading to microcephaly phenotype, treatment with DMSO or AA not only before but also after radiation alleviated DNA damage, cell death, and the microcephaly phenotype. Our results suggest that DMSO and AA are candidates for the radioprotective reagents for brain tumor therapy.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Radioprotective Effects of 16, 16 dimethyl Prostaglandin E2 on Survival and Hematopoiesis are Mediated Through Co-Stimulation of the EP3 and EP4 Receptors.","authors":"Seiji Fukuda, Andrea M Patterson, Tong Wu, Pratibha Singh, P Artur Plett, Hailin Feng, Carol H Sampson, Christie M Orschell, Louis M Pelus","doi":"10.1667/RADE-24-00176.1.S1","DOIUrl":"https://doi.org/10.1667/RADE-24-00176.1.S1","url":null,"abstract":"&lt;p&gt;&lt;p&gt;16, 16 dimethyl-Prostaglandin E2 (dmPGE2) administered prior to lethal irradiation protects against mortality from the hematopoietic acute radiation syndrome (H-ARS). It protects hematopoietic stem (HSC) and progenitor (HPC) cells and accelerates hematopoietic recovery by attenuating mitochondrial compromise, epigenetic downregulation of p53, and inhibition of histone acetylation at the promoters of genes involved in cell cycle, DNA repair and apoptosis. Since PGE2 mediates it effects through 4 conserved G-protein coupled receptors (EP1-4) we utilized highly selective EP receptor agonists to identify the EP receptors mediating radioprotection in H-ARS and evaluated the genes, cellular pathways and biological functions downstream of the EP receptors involved in HSC radioprotection. Radioprotection of mice from lethal radiation exposure was observed for the EP3 agonist sulprostone (65% survival) and the EP4 agonist rivenprost (50% survival), with the combination of EP3 + EP4 agonists providing 100% survival. Misoprostol, a PGE1 analog with similar EP receptor affinities as dmPGE2 also provided &gt;90% survival. The combination of EP3 and EP4 agonists was highly efficacious in accelerating recovery of all peripheral blood cell counts. Analysis of bone marrow HSPC populations from lethally irradiated mice by flow cytometry indicated that the EP3 + EP4 agonist combination trended closest to dmPGE2 in protecting total HSC and HPC, preventing early entry of these cells into cell cycle, and attenuating radiation-induced upregulation of the proapoptotic death receptor Fas, with similar activity also shown by misoprostol. Several genes involved in cell cycle and/or apoptosis control were upregulated (s1pr1, arrdc3, osm) or downregulated (hcar2 and cxcl10) in HSCs by all efficacious agonist treatments. Analysis of gene expression profiles and functional pathway analysis in HSC suggests that the EP4 receptor signals primarily through cAMP/PKA/CREB1, while EP3 signals primarily through a PI3K/Akt pathway initiated through activation of the Ras/Rho GTPases. In the combination setting, EP4 signaling appears dominant. Co-stimulation of EP3 and EP4 gave a stronger z-score for CREB1 activation with EP3 signaling augmenting/enhancing gene expression downstream of EP4 predominantly through CREB1. Comparison of KEGG pathways regulated by dmPGE2 and those regulated by the combination of EP3 + EP4 agonists indicate that both groups' TNF signaling pathways may be key functional components for radioprotection by dmPGE2 in HSC. Differentially expressed genes (DEG) associated with GTPase activity were observed in HSCs from mice treated with both EP3 and EP4 agonists likely contributing to their enhanced radioprotective effect mediated through the PI3K/Akt pathways downstream of both receptors. Some upstream regulators most strongly activated by dmPGE2 in bone marrow stromal cells overlapped with those observed in HSCs, with the most striking similarity being inhibition ","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Murine Model of Radionuclide Lung Contamination for the Evaluation of Americium Decorporation Treatments.","authors":"Trevor Arino, Alexia G Cosby, Jennifer Alvarenga-Vasquez, Kirsten E Martin, Alex Rigby, Adrianna Reece-Newman, Shereen Aissi, Ethan Hallick, Isaac Jaro, Rebecca J Abergel","doi":"10.1667/RADE-25-00001.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00001.1","url":null,"abstract":"<p><p>The hydroxypyridinone ligand 3,4,3-LI(1,2-HOPO) (HOPO), has been previously characterized as a promising chelating agent for in vivo decorporation of actinides, with decorporation being the removal of internally deposited contaminants from the body after exposure. The large majority of relevant literature reports have detailed the efficacy profile of HOPO as a decorporation agent in rodent models, where controlled radionuclide contamination is conducted via intravenous injection. However, this method of contamination does not necessarily reflect an accurate predictive model of the most probable biodistribution of free metal in the body. In the event of a radiological dispersal device or nuclear power plant accident scenario, it is most likely that first responders, military personnel, and victims of the event will be contaminated via air and water transmission. Therefore, research into the efficacy of chelating agents to treat lung-contaminated in vivo models needs to be carried out. Here, we establish a murine model with controlled, reproducible lung contamination using two different radionuclides, 89Zr and 241Am, for orthogonal biodistribution validation by positron emission tomography and ex vivo radioanalysis, respectively. In addition, we report effective chelation treatment of 241Am-contaminated lungs using HOPO, which improves decorporation by up to 40% compared to Ca-DTPA, the current standard of care.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation Between DNA Double-Strand Break Distribution in 3D Genome and Ionizing Radiation-Induced Cell Death.","authors":"Ankang Hu, Wanyi Zhou, Xiyu Luo, Rui Qiu, Junli Li","doi":"10.1667/RADE-24-00277.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00277.1","url":null,"abstract":"<p><p>The target theory is the most classical hypothesis explaining radiation-induced cell death, yet the physical or biological nature of the \"target\" remains ambiguous. This study hypothesizes that the distribution of DNA double-strand breaks (DSBs) within the 3D genome is a pivotal factor affecting the probability of radiation-induced cell death. We propose that clustered DSBs in DNA segments with high-interaction frequencies are more susceptible to leading to cell death than isolated DSBs. Topologically associating domains (TAD) can be regarded as the reference unit for evaluating the impact of DSB clustering in the 3D genome. To quantify this correlation between the DSB distribution in 3D genome and radiation-induced effect, we developed a simplified model considering the DSB distribution across TADs. Utilizing track-structure Monte Carlo codes to simulate the electron and carbon ion irradiation, and we calculated the incidence of each DSB case across a variety of radiation doses and linear energy transfers (LETs). Our simulation results indicate that DSBs in TADs with frequent interactions (case 3) are significantly more likely to induce cell death than clustered DSBs within a single TAD (case 2). Moreover, case 2 is significantly more likely to induce cell death than isolated DSBs (case 1). The curves of the incidence of cases 2 and 3 compared with LETs have a similar shape to the radiation quality factor (Q) used in radiation protection. This indicates that these two cases are also associated with the stochastic effects induced by high-LET radiation. Our study underscores the crucial significance of the 3D genome structure in the fundamental mechanisms of radiobiological effects. The hypothesis in our research offers novel perspectives on the mechanisms that regulate radiobiological effects. Moreover, it serves as a valuable reference for the establishment of mechanistic models that can predict cell survival under different doses and LETs.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparations for Ultra-High Dose Rate 25-90 MeV Electron Radiation Experiments with a Compact, High-Peak-Current, X-band Linear Accelerator.","authors":"Haytham H Effarah, Trevor Reutershan, Michael W L Seggebruch, Martin Algots, Alexander Amador, Janet Baulch, Olivia G G Drayson, Frederic V Hartemann, Yoonwoo Hwang, Agnese Lagzda, Ferenc Raksi, Charles L Limoli, Christopher P J Barty","doi":"10.1667/RADE-24-00120.1","DOIUrl":"10.1667/RADE-24-00120.1","url":null,"abstract":"<p><p>The Distributed Charge Compton Source (DCCS) developed by Lumitron Technologies, Inc. has produced a 25-MeV electron beam with 1.7-nC macrobunches at a 100-Hz repetition rate from a compact, high-gradient X-band (11.424 GHz) accelerator. The DCCS is currently being commissioned to produce 100-MeV-class electrons, well within the very high energy electron (VHEE) energy regime, with macrobunch charges of up to 25 nC at repetition rates up to 400 Hz. The DCCS is also designed to produce imaging X rays through Laser Compton scattering. This work aims to describe the preparations for the first dosimetry experimental campaign using this accelerator system at energies ranging from 25 MeV to 90 MeV through hardware development and Monte Carlo (TOPAS) simulation studies. A significant goal of these preparations is to configure the machine so that it can be used to both image with X rays and subsequently treat with VHEEs without movement of the animal model under study. At ultra-high dose rates, this X-ray image-guided electron source could be used to investigate dose-rate dependent differential sparing of normal and malignant biological tissue, known as the FLASH effect. An indium-tin-oxide-coated, 100-μm-thick diamond window was obtained and installed in a custom flange assembly to act as the electron/X-ray vacuum exit window. Simulations at 25 MeV suggest that a scattering foil and collimator can shape the output of the accelerator to produce a 12-mm-diameter, flat-field, circular beam with a 1.7-nC macrobunch charge. This corresponds to an entrance dose of 10 Gy in less than 100 ms. These initial results highly motivate an experimental campaign toward investigating VHEE FLASH using the DCCS at Lumitron Technologies, Inc.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"223-235"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}