Radiation research最新文献

{"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}

{"title":"Occupational Exposure to Low Dose Ionizing Radiation and the Incidence of Surgically Removed Cataracts and Glaucoma in a Cohort of Ontario Nuclear Power Plant Workers.","authors":"Paul J Villeneuve, Brianna Frangione, Robert Talarico, Tim Prendergast, Chenchung Yu, Gagan Gill, Lydia Zablotska","doi":"10.1667/RADE-24-00050.1","DOIUrl":"10.1667/RADE-24-00050.1","url":null,"abstract":"<p><p>Ionizing radiation is a human carcinogen and has been shown to increase the risk of non-cancerous ocular disorders. Specifically, findings from epidemiological studies suggest that ionizing radiation leads to the development of cataracts and to a lesser extent glaucoma, however, there are uncertainties of these risks at lower exposures. We analyzed data from a cohort of 60,874 Ontario Nuclear Power Plant (NPP) workers within the Canadian National Dose Registry (NDR). These workers were monitored for whole-body exposure to ionizing radiation using dosimeters, with exposure estimates derived for each year of employment. Incident cases of surgically removed cataracts and glaucoma were identified through the record linkage of occupational histories to administrative health data for Ontario between 1991 and 2022. We compared the incidence of surgically removed cataracts and glaucoma in the cohort to Ontario's general population using indirect age- and sex-standardization with matching by place of residence. We evaluated exposure-response relationships with internal cohort comparisons using age-, sex-, and calendar-period-adjusted Poisson regression. The relative risks of cataract and glaucoma were estimated across categorical measures of whole-body dose [Hp(10)] from exposure to radiation (lagged 5 years). In total, 32,855 of the 60,874 workers (58%) had a positive cumulative dose exceeding the minimum reportable threshold. Among these workers, the mean cumulative whole-body lifetime dose at end of follow-up was 23.7 mSv (interquartile range: 1.1-26.4 mSv, maximum = 959.3 mSv). Overall, 4,401 (7.2%) of workers developed glaucoma, while 2,939 (4.8%) underwent cataract-removal surgery. There was no evidence of a dose-response relationship between cumulative whole-body dose ionizing radiation (lagged 5 years) and glaucoma, but some for surgically removed cataracts. Specifically, among workers with a cumulative exposure of greater than 50 mSv relative to those with an exposure of less than 0.25 mSv, the relative risks of incident glaucoma and cataract removal surgery were 0.91 (95% CI: 0.81-1.05) and 1.13 (95% CI: 0.97-1.33), respectively. The linear excess risks per 100 mSv (lagged 5 years) for cataract removal surgery was 0.055 (95% CI: -0.042 to 0.163). Our findings provide some evidence that ionizing radiation increases the risk of cataracts but not glaucoma in an occupational cohort whose lifetime cumulative dose rarely exceeded 30 mSv.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"271-283"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449665","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":"What's in a Proton FLASH Beam? Characterizing Ultra-High Dose Rate Protons Using a Commercial Plastic Scintillator.","authors":"Yannick Poirier, Kevin E Byrne, Gulakhshan Hamad, François Therriault-Proulx, Kai Jiang, Wei Deng, Amit Sawant, Sina Mossahebi","doi":"10.1667/RADE-24-00117.1","DOIUrl":"10.1667/RADE-24-00117.1","url":null,"abstract":"<p><p>While biological studies of the FLASH effect in proton beams have mainly been performed in the plateau region at maximum beam energy and current, this type of delivery has limited clinical applications. Naturally, it is anticipated that plans to treat patients clinically with FLASH-radiotherapy (FLASH-RT) will capitalize on the Bragg peak. However, as the proton spot widens with depth, the time required to deliver the entire dose to any single point increases. This decreases the dose rate, making the ultra-high dose rates required to trigger the FLASH effect harder to achieve over large areas. Importantly, the dose rate is difficult to measure directly. Time and dose linearity of a fast-resolving commercial plastic scintillation detector were characterized against an ionization chamber. The percent depth dose of a 250 MeV proton beam scanned across a small area (3.5 × 3.5 cm2) was measured at depths of 3-40 cm in solid water. The plastic scintillation detector was used to evaluate the instantaneous and voxel-averaged dose rates as a function of depth for conventional (2 nA nozzle current) and ultra-high dose rate (100 nA) beams. The response of the plastic scintillation detector was shown to be linear with time (±2.5 ms) and absorbed dose (±2%). The scintillator and ionization chamber measurements agreed well as a function of depth (and therefore energy) within 2% for depths <34 cm. Beyond 34 cm, expected quenching effects were observed in the plastic scintillation detector. The voxel-averaged dose rate varied from 52.7 Gy/s at the entrance to 29.3 Gy/s at mid-depth, to 70.4 Gy/s near the Bragg peak, while the maximum instantaneous dose rate decreased from 472 Gy/s near the entrance to 236 Gy/s at the Bragg peak. The plastic scintillation detector has proven useful for investigators to evaluate the complex relationship between dose rate and pencil-beam scanning ultra-high dose rate beam characteristics. There is a loss of dose rate near the Bragg peak due to spot widening, which may acutely impact our ability to exploit the FLASH effect for sparing normal tissues upstream of the intended treatment area. A thorough preclinical investigation of whether the FLASH effect is maintained near the Bragg peak is necessary before this technique can begin translation to the clinic.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"201-213"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616807","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":"Plasmid DNA Strand Breaks Are Dose Rate Independent at Clinically Relevant Proton Doses and Under Biological Conditions.","authors":"Louis V Kunz, Robert Schaefer, Houda Kacem, Jonathan Ollivier, Michele Togno, Flore Chappuis, Damien Weber, Anthony Lomax, Charles L Limoli, Serena Psoroulas, Marie-Catherine Vozenin","doi":"10.1667/RADE-24-00118.1","DOIUrl":"10.1667/RADE-24-00118.1","url":null,"abstract":"<p><p>We investigated the effect of proton FLASH radiation on plasmid DNA. Purified supercoiled pBR322 plasmids were irradiated with clinical doses (≤10 Gy) of protons at ultra-high and conventional dose rates using the Paul Scherrer Institute (PSI) isochronous cyclotron. The proton beam in this clinical facility has been validated to produce the FLASH effect in preclinical models. Plasmid samples were irradiated under various oxygen tensions, scavenger levels, pH conditions and Fe (II) concentrations as these biochemical parameters vary across tissues and tumors. Over the range of doses used, plasmid DNA strand breaks were found to be dose rate independent at all conditions investigated. Irradiation within the Bragg peak and spread-out Bragg peak increased clustered strand breaks, except in the presence of scavengers. With this model system, we demonstrate conclusively that plasmid DNA strand breakage is dose rate independent at doses below 10 Gy and does not constitute a high throughput assay endpoint predictive of the biological effect of FLASH.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"214-222"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516355","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":"Systematic Study of Silicon Carbide Detectors and Beam Current Transformer Signals for UHDR Single Electron Pulse Monitoring.","authors":"C Okpuwe, G Milluzzo, D Coves, T Delaviere, D Del Sarto, M De Napoli, F Di Martino, G Felici, L Lanzanò, L Masturzo, J Pensavalle, E Touzain, M Camarda, F Romano","doi":"10.1667/RADE-24-00139.1","DOIUrl":"10.1667/RADE-24-00139.1","url":null,"abstract":"<p><p>The use of ultra-high dose rate beams (UHDR) (> 40 Gy/s) for radiotherapy, despite its advantage of exhibiting the FLASH effect that improves the sparing of healthy tissues, faces challenges in dosimetry and beam monitoring since standard dosimeters like the ionization chamber experience saturation effects at such high dose rates. Silicon carbide (SiC) detectors have recently been demonstrated to be dose-rate independent with low-energy pulsed electron beams up to an instantaneous dose rate of 5.5 MGy/s, and has emerged as a reliable alternative technology for dosimetry in FLASH-RT. This study explored the suitability of using the SiC detector for measuring intra-pulse instantaneous dose rates, which are necessary for monitoring fluctuations within the pulse of UHDR pulsed electron beams. The experiments reported were conducted using UHDR electron beams accelerated at 9 MeV by an ElectronFlash linac and using varying different beam parameters, such as the beam current (i.e., different dose per pulse) and pulse width settings. The temporal single pulse shape signals were measured with a 10 µm thick, 4.5 mm2 area SiC detector for different configurations and compared with a well-characterized AC current transformer (ACCT) (which served as the standard monitoring system of the accelerator), and with a second ACCT placed at the same location as the SiC detector (i.e., after the applicator at the irradiation point). The results show a high level of agreement between the signals of the SiC detector and ACCT placed after the applicator at around the irradiation point. This underscores the potential of the SiC detector and the ACCT to be used for monitoring instantaneous dose rates within a pulse. Furthermore, since use of the SiC detector and ACCT are based on different physical principles, they can provide complementary beam information. A combination of the two has the potential to provide insight about a variety of variables of interest for UHDR beams. However, some discrepancies were observed when comparing the SiC signals with the ACCT installed in the LINAC, which increased linearly with decreasing dose per pulse. Further studies are required to better understand these observations.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"236-245"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493400","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":"PRMT7 Inhibitor SGC3027 Enhances Radiotherapy Efficacy via Activating ATM Kinase in Non-Small Cell Lung Carcinoma.","authors":"Ya Heng, Feifei Wang, Zhonghui Zhang, Zebang Lin, Dahai Zhao, Qiuling Li","doi":"10.1667/RADE-24-00242.1","DOIUrl":"10.1667/RADE-24-00242.1","url":null,"abstract":"<p><p>Non-small-cell lung cancer (NSCLC) is the leading cause of tumor-related death in humans. Radiotherapy is a crucial strategy for NSCLC treatment, although its effectiveness is limited by the radio-resistance of tumor cells. Our current research finds that the protein arginine methyltransferase 7 (PRMT7) is upregulated in NSCLC and correlates with poor prognosis. Pharmacological inhibition of PRMT7 by SGC3027, a specific small-molecule PRMT7 inhibitor, suppresses the proliferation, migration and invasion of NSCLC. Combining irradiation with SGC3027 strengthens the impact of irradiation on the biological behaviors of NSCLC cells. We also find that SGC3027 specifically activates ATM kinase and its downstream cell cycle checkpoint kinases to enhance radiobiological response in NSCLC. These findings underscore the promising therapeutic potential of PRMT7 inhibitors as well as combining PRMT7 inhibition with irradiation exposure for effective NSCLC therapies.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"284-292"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524037","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":"Effects of Whole-Body Carbon-Ion Beam Irradiation on Bone Marrow Death in Mice and an Examination of Candidates for Protectors or Mitigators against Carbon-Ion-Beam-Induced Bone Marrow Death.","authors":"Megumi Ueno, Shuichi Setoguchi, Kazuhisa Matsunaga, Ken-Ichiro Matsumoto, Jiro Takata, Kazunori Anzai","doi":"10.1667/RADE-23-00253.1","DOIUrl":"10.1667/RADE-23-00253.1","url":null,"abstract":"<p><p>The present study examined the effects of whole-body carbon-ion-beam irradiation on bone marrow death in mice and investigated whether compounds/materials, which were identified as efficient radio-protectors or mitigators against X-ray-radiation-induced bone marrow death, were also effective against the carbon-ion-beam-induced death of mice. Amifostine and cysteamine were used as radio-protectors and zinc-containing heat-killed yeast (Zn-yeast) and γ-tocopherol-N,N-dimethylglycine ester (γTDMG) as radio-mitigators. Amifostine or cysteamine was intraperitoneally administered in a single injection of 1.95 mmol/kg body weight 30 min before whole-body carbon-ion-beam irradiation. Zn-yeast or γTDMG was administered in a single intraperitoneal injection of 100 mg/kg body weight immediately after whole-body carbon-ion-beam irradiation. The absorbed dose dependence of the 30-day survival rate after carbon-ion-beam irradiation was analyzed. The biological effectiveness of carbon-ion-beam irradiation (LD50/30 = 5.54 Gy) was estimated as 1.2 relative to X-ray irradiation (LD50/30 = 6.62 Gy). The dose reduction factors (DRF) of amifostine, cysteamine, Zn-yeast, and γTDMG estimated for carbon-ion-beam irradiation were 1.75, 1.53, 1.16, and 1.15, respectively. Radio-protectors and -mitigators that were effective against photon irradiation also exhibited efficacy against carbon-ion-beam irradiation; however, the DRF for carbon-ion-beam irradiation was slightly smaller than that for photon irradiation. Based on the radio-protective effects of amifostine and cysteamine, the contribution of ROS/free radicals to carbon-ion-beam-induced bone marrow death was 70-90% to that of photon irradiation. Since the suppression of tumor growth by carbon-ion-beam irradiation was not inhibited by the treatment with γTDMG or Zn-yeast, both mitigators have potential as normal tissue-selective protectors in carbon-ion irradiation.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"246-256"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399780","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":"Timosaponin AIII Enhances Radiosensitivity in Breast Cancer through Induction of ROS-Mediated DNA Damage and Apoptosis.","authors":"Huiting Peng, Bingqing Cui, Jianming Wei, Min Yuan, Wenjuan Liu, Jing Shi, Yuguo Liu","doi":"10.1667/RADE-24-00087.1","DOIUrl":"10.1667/RADE-24-00087.1","url":null,"abstract":"<p><p>Breast cancer is a commonly diagnosed cancer, while resistance to radiation therapy remains an important factor hindering the treatment of patients. Timosaponin AIII (Tim AIII) is a steroidal saponin from the Anemarrhena asphodeloides. Its pharmacologic effects and mechanisms for enhancing radiotherapy remain largely unknown. This study investigates Tim AIII and aims to unravel the underlying mechanisms. Experiments, including cell cloning, scratch assays, cell cycle, apoptosis assays, immunofluorescence staining, and reactive oxygen species (ROS) assessments, were conducted on breast cancer cell lines MDA-MB-231 and JIMT-1 to investigate the impact of Tim AIII combined with radiation. Western blot analyses were used to detect γ-H2AX expression, ROS-related pathways, ATM-CHK2, and AKT-MTOR pathways. Subcutaneous tumor experiments in nude mice confirmed in vivo radiation sensitization. When combined with radiation, Tim AIII significantly inhibited cell clone formation, impeded cancer cell migration, increased G2/M phase arrest and apoptosis. Immunofluorescence showed prolonged γ-H2AX signals. Molecular investigations indicated Tim AIII amplified radiation-induced ROS production, inducing ROS-mediated DNA damage and apoptosis. It activated ATM-CHK2 while inhibiting the AKT-MTOR pathway. Tim AIII enhances radiation sensitivity in breast cancer cells, both in vitro and in vivo. Through ROS-mediated DNA damage and apoptosis, activation of ATM/Chk2 and inhibition of the AKT-MTOR pathway induce G2/M phase arrest, ultimately boosting radiation sensitivity via the mitochondrial-mediated apoptotic pathway.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"257-270"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399819","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":"Widespread Multimorbidity in a Cohort of Aging, Radiation-exposed Rhesus Macaques.","authors":"Ellen E Quillen, George W Schaaf, Jamie N Justice, Gregory O Dugan, Brendan Johnson, Colin Reed, John D Olson, J Mark Cline","doi":"10.1667/RADE-24-00014.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00014.1","url":null,"abstract":"<p><p>Delayed effects of acute radiation exposure (DEARE) and radiation late effects are a suite of conditions that become apparent months to years after initial exposure to radiation in both humans and non-human primates. Many of these disorders, including cardiac complications, insulin resistance, bone loss, hypertension, and others, are also more common among aging cohorts independent of radiation exposure. This study characterized disease incidence, age of onset, and multimorbidity for 20 common, chronic diseases in 226 irradiated and 51 control rhesus macaques (Macaca mulatta) from the Wake Forest Non-Human Primate Radiation Late Effects Cohort (RLEC) to identify the excess risk of chronic disease caused by radiation-induced tissue damage. Irradiated animals were exposed to 4.0-8.5 Gy of ionizing radiation (mean 6.17 ± 1.29 Gy) one year on average prior to joining the cohort. In addition to the acute impact of early-life irradiation, these animals have been aging postirradiation for up to 15 years (mean 5.2 ± 3.0 years). Lifespan is an average of 5.1 years shorter in irradiated animals and radiation is associated with significantly increased rates of periodontitis, cataracts, testicular atrophy, tumors, diabetes, and brain lesions. While most of these chronic diseases occur in non-irradiated macaques, irradiated animals have significantly earlier age of onset for periodontitis, cataracts, bone loss, being overweight, and arthritis. This accelerated onset leads to 2.9 ± 1.9 comorbid conditions among irradiated animals compared to 1.9 ± 1.2 diagnoses among controls by young adulthood (age 8) and 5.2 ± 2.4 compared to 3.4 ± 1.8 conditions by middle age (15 years). Subsets of these comorbid conditions cluster among animals with fibrosis-related disorders (diabetes, lung injury, liver disease, kidney disease, heart disease, and tumors) commonly diagnosed together independent of prevalence. A second cluster of comorbidities centers around bone loss and is associated with being underweight and female reproductive problems. While there are significant differences in disease burden between irradiated and control animals, there was no dose effect of radiation on lifespan, age to first diagnosis, or comorbidities and substantial heterogeneity across each of these measures. This underlying heterogeneity in response to radiation suggests the existence of a yet unidentified determinant of resilience.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586681","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}