Shannon Hartzell, Fada Guan, Giuseppe Magro, Paige Taylor, Christine B Peterson, Stephen F Kry
{"title":"Quantifying Sensitivity of Carbon RBE Models to Reference Parameter Variations.","authors":"Shannon Hartzell, Fada Guan, Giuseppe Magro, Paige Taylor, Christine B Peterson, Stephen F Kry","doi":"10.1667/RADE-24-00162.1","DOIUrl":"10.1667/RADE-24-00162.1","url":null,"abstract":"<p><p>Models used to calculate the relative biological effectiveness (RBE) of carbon-ion radiotherapy include the microdosimetric kinetic model (MKM), stochastic MKM (SMKM), repair-misrepair-fixation (RMF) model, and local effect model I (LEM). We compared the sensitivities of these models to variations in input biological and reference parameters. We used Monte Carlo simulations of clinically realistic carbon-ion beams incident on a phantom and scored input parameters for RBE models (kinetic energy, microdosimetric spectra, double-strand break yield, and physical dose). We combined data with cell- and model-specific parameters to calculate the linear (α) and quadratic (β) components of the carbon-ion beam, which were used along with the reference α and β values and dose to calculate RBE. Model sensitivity to parameters was quantified by statistically introducing uncertainty into independent parameters and sampling the resultant RBE. To assess histological differences contributing to variations in the RBE, we also used various reference cell lines. We recalculated the RBE using different reported datasets within individual cell lines to compare inter- and intra-cell line variability. The variability introduced by inherent measurement and estimation uncertainty was typically 26% for the microdosimetric models, 25% for the RMF model, and 30% for the LEM at the 1-σ level. The variability across cell lines, which averaged 27% for the microdosimetric models and 2.5% for the RMF model, was similar to the intra-cell line variability in the RBE as calculated with unique datasets for an individual cell line. While the focus is largely on comparing models, the results of this study indicate that the variation in RBE within each model, based solely on reference parameters, is substantial. Our findings indicate that the selection of input parameters is of comparable importance to the choice of cell line and even the RBE model. This study provides insight into model robustness and emphasizes the need for continued computational and in-vitro RBE research.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"113-126"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christopher A Loffredo, Felicia D Atkinson, Bhaskar Kallakury, Jan Blancato, Galina V Zhuntova, Evgeniya S Grigoryeva, David S Goerlitz, Timothy J Jorgensen, Gleb V Sychugov, Scott C Miller, Tamara V Azizova
{"title":"Angiosarcoma of the Liver and Other Hepatic Malignancies in the Russian Cohort of Mayak Nuclear Workers.","authors":"Christopher A Loffredo, Felicia D Atkinson, Bhaskar Kallakury, Jan Blancato, Galina V Zhuntova, Evgeniya S Grigoryeva, David S Goerlitz, Timothy J Jorgensen, Gleb V Sychugov, Scott C Miller, Tamara V Azizova","doi":"10.1667/RADE-23-00240.1","DOIUrl":"10.1667/RADE-23-00240.1","url":null,"abstract":"<p><p>Human occupational exposure to ionizing radiation has been linked to increased risks of developing cancers, including solid tumors. In particular, 239Pu, used in the production of nuclear weapons, has been associated with a higher risk of malignancies of the lungs, liver, and bones, but the specific patterns of malignant histology have not been well described in humans. We assessed the pathological characteristics of liver cancers that occurred in a Russian cohort of nuclear workers from the Mayak Production Association, with a special emphasis on angiosarcoma, and studied the relationships between dosimetry, sex, and histology. The subjects included two main groups of workers whose biological specimens were collected during autopsies: thirty-one were diagnosed with liver cancers (cases), and 38 workers were cancer-free (controls). An independent pathologist reviewed all liver tissues from these cancer cases and performed immunohistochemistry to confirm the diagnoses (angiosarcoma, hepatocellular carcinoma, or cholangiocarcinoma). A third group consisted of 36 workers who developed liver cancer but for whom no biological samples were available. Radiation dose levels, along with sex and age distributions, were compared statistically among the three types of liver tumors and the control groups. There was a predominance of females (9 of 13, 69%) among the workers who developed angiosarcoma of the liver, whereas a male predominance characterized both hepatocellular carcinoma (9 of 9, 100%) and cholangiocarcinoma (8 of 9, 89%). A male predominance was also observed in the group of workers with liver cancer but without biological samples (22 of 36, 61%) and in the group of workers without liver cancer (30 of 38, 79%). Occupational differences were evident, with angiosarcoma patients who had biological samples representing the largest proportion (9 of 13) of plutonium metallurgical plant workers (the most highly exposed occupation to plutonium in the cohort), while the remainder (4 of 13) occurred among the radiochemical plant workers. Compared to other groups, those workers with biological samples who developed angiosarcoma had the largest accumulated and widest range of external doses absorbed by the liver, as well as the highest absorbed doses of 239Pu to the liver. Females with biological samples who developed liver cancer also had some of the highest accumulated doses from 239Pu, exceeding 1 Gy in some instances. Our observations of histology, sex, occupation, and dose patterns provide possible clues to the unusual pattern of liver malignancies, particularly angiosarcoma, related to aspects of plutonium exposure.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"101-112"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143265","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}
Lanyn P Taliaferro, Jeffrey C Buchsbaum, Andrea L DiCarlo, Cinnamon A Dixon, Francesca Macchiarini, Merriline M Satyamitra, Mercy PrabhuDas, Michael W Rudokas
{"title":"Understudied Populations in Radiation Exposure Research: Needs, Challenges, and Mitigation Strategies.","authors":"Lanyn P Taliaferro, Jeffrey C Buchsbaum, Andrea L DiCarlo, Cinnamon A Dixon, Francesca Macchiarini, Merriline M Satyamitra, Mercy PrabhuDas, Michael W Rudokas","doi":"10.1667/RADE-24-00263.1","DOIUrl":"10.1667/RADE-24-00263.1","url":null,"abstract":"<p><p>This workshop examined the effects of ionizing radiation on certain understudied populations, including pregnant/lactating, in utero, pediatric, and geriatric individual. Research using animal models has revealed significant age- and condition-related differences in radiation-induced injuries, highlighting the need for tailored triage and treatment strategies. Historical data from Hiroshima, Nagasaki, and Chernobyl further support these findings, demonstrating that radiation effects lead to wide-ranging issues with unique profiles during pregnancy, childhood and elderly age. While some research has been conducted on these groups, ethical and logistical challenges make it difficult to study these populations extensively. Therefore, developing alternative approaches that offer promising avenues for further research is critical. Radiation-induced biomarkers and biodosimetry also show age-related differences, including distinctive metabolic disruptions, necessitating further validation of biodosimetry tools. These findings emphasize the importance of considering age, sex, and demographic factors in preclinical and clinical radiation research to develop treatments that improve outcomes of understudied populations after a radiological or nuclear public health emergency.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"154-171"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12257501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"PNA-FISH-based Chromosome Aberration Frequency and Serum IL-6 as Predictive Biomarkers for Radiation Therapy-induced Pneumonitis in Lung Cancer Patients.","authors":"Gloriamaris Loy-Caraos, Nobuki Imano, Ikuno Nishibuchi, Yuji Murakami, Nafiseh Mirkatouli, Seiko Hirota, Shinji Yoshinaga, Yoshitaka Kamimura, Yuri Kawashima, Jiying Sun, Satoshi Tashiro","doi":"10.1667/RADE-25-00013.1","DOIUrl":"10.1667/RADE-25-00013.1","url":null,"abstract":"<p><p>Accurate prediction of symptomatic radiation therapy-induced pneumonitis (RT-IP) remains an important clinical challenge. Currently, mean lung dose and volume of the lungs receiving a 20 Gy threshold of ≤20 Gy and ≤35%, respectively, are utilized to reduce the incidence of pneumonitis to 20%. However, its occurrence is not entirely predictable even at the recommended threshold levels. Hence, in this study, we aimed to evaluate several biological markers, specifically chromosome aberrations by peptide nucleic acid fluorescence in situ hybridization (PNA-FISH), γH2AX, serum IL-6, and IL-17, as potential predictors of symptomatic (grade ≥2) radiation therapy-induced pneumonitis. We prospectively enrolled patients with locally advanced lung cancer. Peripheral blood samples were collected from eleven patients before, during (2 Gy, 20 Gy, 60/66 Gy), and one month after chemoradiotherapy. We then compared these biomarkers between overreactors (grade ≥2 RT-IP) and non-overreactors (grade 0 to 1 RT-IP). Our findings show that chromosome aberration frequency, serum IL-6, and IL-17 after 20 Gy are higher in overreactors than in non-overreactors. Moreover, overreactors accumulated more complex aberrations, such as tricentrics, quadricentrics, and quintacentrics. While chromosome aberration frequency correlated with mean lung dose and IL-17, a pneumonitis marker, IL-6 correlated with the irradiated volume after 20 Gy. Receiver operating characteristic curve analysis further showed that chromosome aberration frequency and IL-6 have the highest specificity for predicting grade ≥2 RT-IP among the assays. In conclusion, we demonstrated the superior predictive capability of PNA-FISH-based chromosome aberration frequency and serum IL-6 for radiation therapy-induced pneumonitis in lung cancer patients. This supports the usefulness of these biomarkers for predicting radiation therapy-induced pneumonitis.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"127-142"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234964","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}
Jeffrey C Buchsbaum, Henry F VanBrocklin, Reinier Hernandez, Ellen M O'Brien, Heather M Hennkens, Dmitri G Medvedev, Roger W Howell, Freddy E Escorcia, Yuni K Dewaraja, Abhinav K Jha, Anuj J Kapadia, Greeshma Agasthya, Arman Rahmim, Babak Saboury, Kristian Myhre, Sandra Davern
{"title":"Computational Modeling to Advance Novel Medical Isotopes for Radiotheranostics: A DOE-NIH Joint Workshop Executive Summary.","authors":"Jeffrey C Buchsbaum, Henry F VanBrocklin, Reinier Hernandez, Ellen M O'Brien, Heather M Hennkens, Dmitri G Medvedev, Roger W Howell, Freddy E Escorcia, Yuni K Dewaraja, Abhinav K Jha, Anuj J Kapadia, Greeshma Agasthya, Arman Rahmim, Babak Saboury, Kristian Myhre, Sandra Davern","doi":"10.1667/RADE-25-00MR1.1","DOIUrl":"10.1667/RADE-25-00MR1.1","url":null,"abstract":"<p><p>The DOE-NIH Joint Workshop on Computational Modeling to Advance Novel Medical Isotopes for Radiotheranostics, held on September 27, 2024, brought together experts from government, academia, and industry to address critical challenges in radionuclide production and clinical translation. The workshop emphasized interdisciplinary collaboration, particularly between the Department of Energy (DOE) and the National Institutes of Health (NIH), to strengthen the domestic isotope supply, streamline regulatory pathways, and further integrate computational tools into radiopharmaceutical therapy (RPT). Key discussions explored the role of AI-driven modeling, machine learning, and digital twin technologies in optimizing dosimetry, dynamically personalizing treatments, and reducing time to clinical adoption. Advances in predictive computational modeling were highlighted as essential for improving radionuclide yield, purity, and synthesis efficiency. Regulatory considerations and equitable access were central themes, with participants advocating for harmonized global standards, adaptive trial designs, and expanded infrastructure for clinical implementation. DOE computational and production infrastructure was emphasized. Future priorities identified include increased investment in radionuclide production infrastructure, expanded workforce development in radiopharmaceutical sciences and computational modeling, and the creation of robust public-private partnerships. The workshop concluded that continued strategic collaboration and sustained resources will be vital for advancing next-generation radiotheranostics, ensuring safe and effective therapies accessible to all patients.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"75-79"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014554","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}
Le Ma, Zhihe Hu, Yan Chen, Zhuo Cheng, Chunmeng Shi
{"title":"Characterization of Two Stable Biodosimeters for Absorbed Ionizing Radiation Dose Estimation in Multiple Combined Injury Models.","authors":"Le Ma, Zhihe Hu, Yan Chen, Zhuo Cheng, Chunmeng Shi","doi":"10.1667/RADE-24-00261.1","DOIUrl":"10.1667/RADE-24-00261.1","url":null,"abstract":"<p><p>Radiation damage and deposition caused by radiological or nuclear public health incidents (e.g., accidents or attacks) may lead to acute radiation syndrome and other complications. Accurate and effective radiation dose assessment is necessary for triaging irradiated patients and determining treatment plans. However, there is no systematic evaluation of whether radiation biodosimetry is affected by comorbidities. The weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEG) co-analysis of the RNA-sequencing data in human peripheral blood after irradiation from the Gene Expression Omnibus (GEO) database identified seven radiation-specific genes, including five upregulated genes and two downregulated genes. Five radiation-specific genes (CCNG1, CDKN1A, GADD45A, GZMB, PHLDA3) showed a strong linear correlation with the total-body X-ray radiation model. The above five genes were used to validate further several radiation combined injury models, including infection, trauma, and burns, while considering different sexes and ages in animal studies on the radiation response from 0 to 10 Gy. The receiving operator characteristic (ROC) curve analysis revealed that the CCNG1 and CDKN1A genes performed the best in radiation dose-response across both mice and humans. Moreover, the CCNG1 protein could accurately predict the absorbed doses for up to 28 days after exposure (>95%). Our findings suggested that the CCNG1 and CDKN1A mRNA performed optimally in radiation dose response, independent of trauma, burns, age, and sex. Additionally, the CCNG1 protein revealed a strong linear correlation between radiation dose and time postirradiation. Our study demonstrated the potential feasibility of using CCNG1 and CDKN1A as injury biomarkers in radiation accident management.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"27-45"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045952","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}
Yueshan Feng, Jiaxing Yu, Lixin Xu, Haohan Lu, Hongyun Zhang, Zhengsong Li, Roberta Kungulli, Tao Hong, Mo Zhang, Jie Lu, Hongqi Zhang, Sishi Xiang
{"title":"Development of an Experimental Platform for Gamma Knife Radiosurgery in Mouse Brains.","authors":"Yueshan Feng, Jiaxing Yu, Lixin Xu, Haohan Lu, Hongyun Zhang, Zhengsong Li, Roberta Kungulli, Tao Hong, Mo Zhang, Jie Lu, Hongqi Zhang, Sishi Xiang","doi":"10.1667/RADE-24-00198.1","DOIUrl":"10.1667/RADE-24-00198.1","url":null,"abstract":"<p><p>The limited availability of post-Gamma Knife radiosurgery (GKRS) samples and the unsuitability of clinical GKRS devices for small animals highlight the need to develop devices that enable the application of a clinical GKRS device in mouse models. This study introduces a novel platform specifically designed for utilizing the Leksell Gamma Knife in mouse studies. The 3D-printed device comprises a positioning platform and a head fixation device. Six-week-old C57BL/6N mice underwent irradiation targeting the left caudate putamen (CPu) or left anterior frontobase areas. Clinical Gamma Knife prescription doses (central radiation doses of 80 Gy, 60 Gy, 50 Gy, 40 Gy, 20 Gy, and 10 Gy) were administered as single exposures. Dose conversion experiments confirmed that the actual radiation dose delivered to mice was consistently 1.5-fold higher than the planned clinical dose. MRI and H&E staining revealed clear radiation necrosis (RN) in the targeted areas when the planned clinical dose of 80 Gy was applied to the CPu and anterior frontobase, confirming the device's accuracy. γ-H2AX staining showed significant DNA double-strand breaks in the targeted region, particularly after a planned clinical dose of 40 Gy and higher. H&E staining also indicated parenchymal hemorrhage, tissue loss, and edema in the targeted areas among groups exposed to the planned clinical central doses of 80 Gy, 60 Gy, and 50 Gy. Immunofluorescence staining of CD68, IBA1, and NeuN showed significant neuroinflammation in the targeted areas of the high-dose groups (planned clinical doses of 80 Gy, 60 Gy, 50 Gy, or 40 Gy), characterized by increased microglia activation, macrophage infiltration, and neuronal death. This study developed a novel mouse platform for the Leksell Gamma Knife, enabling precise GKRS in mouse brains. For adult C57BL/6N mice, a planned clinical central dose of 40 Gy may be considered a suitable threshold for radiation-induced brain injury.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"46-58"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051017","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}
Evan L Pannkuk, Evagelia C Laiakis, Guy Y Garty, Igor Shuryak, Kamendra Kumar, Shubhankar Suman, Shanaz A Ghandhi, Yuewen Tan, Brian Ponnaiya, Xuefeng Wu, Sally A Amundson, David J Brenner, Albert J Fornace
{"title":"Sex Differences in Urinary Metabolite Profiles between Survivors and Non-Survivors of Radiation-induced Lung Injury in the C57L/J Murine Model.","authors":"Evan L Pannkuk, Evagelia C Laiakis, Guy Y Garty, Igor Shuryak, Kamendra Kumar, Shubhankar Suman, Shanaz A Ghandhi, Yuewen Tan, Brian Ponnaiya, Xuefeng Wu, Sally A Amundson, David J Brenner, Albert J Fornace","doi":"10.1667/RADE-25-00066.1","DOIUrl":"10.1667/RADE-25-00066.1","url":null,"abstract":"<p><p>Novel biodosimetry assays are needed to categorize both acute ionizing radiation injury and delayed effects of radiation exposure, such as radiation-induced lung injury (RILI) -associated mortality. In this study, we utilized the C57L/J mouse model, a well-established system for replicating the clinical pathology of RILI. Lung injury was induced using a combination of neutron total-body irradiation (TBI) (30% of total dose +7% of total dose concomitant gamma rays) and whole-thoracic X-irradiation (WTI) boost for the balance of the required dose at total doses of 9, 9.5, 10 and 10.5 Gy. The animals were monitored for a period of 180 days postirradiation to evaluate the progression of injury. Both male and female mice were included in the study, with cohorts exposed to either sham dose (0 Gy) or 100% X-ray WTI at 11.35 Gy (LD50/180 dose) to serve as controls. Tissue injury was characterized using whole-body plethysmography, histopathology, and targeted lipidomics. Urinary metabolites were detected using untargeted metabolomic profiling to determine if they could serve as early predictors of RILI survival. A survival rate of 40-45% was observed at 180 days postirradiation consistent with the established LD50/180 value for WTI (11.35 Gy), except at 10.5 Gy, where survival dropped to 20%. Irradiated mice exhibited increased pulmonary immune infiltration and collagen deposition, reduced alveolar spaces, thickened bronchiolar walls, and dose-independent alterations in lipid profiles that were not sex-specific. We developed a multiplex urinary metabolite panel that was associated with RILI and radiation exposure. Some compounds were statistically different between sham-irradiated male and female mice, with sex specific differences at 120 days were observed for homocitrulline, xanthosine, acetyl-arginine, methylhistidine, niacinamide, xanthurenic acid, cyclic adenosine monophosphate, taurine, and prolyl-proline urinary metabolite levels. Baseline differences in sham-irradiated C57L/J mice show sex needs to be considered as a variable when developing biomarker panels for long-term RILI effects. However, urinary metabolite panels can provide excellent to very good sensitivity and specificity at predicting survival from RILI.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alana D Carpenter, Issa Melendez-Miranda, Yaoxiang Li, Jeyalakshmi Kandhavelu, Oluseyi O Fatanmi, Stephen Y Wise, Amrita K Cheema, Vijay K Singh
{"title":"Proteomic Changes in Preterminal Serum Samples of Rhesus Macaques Exposed to Two Different Doses of Acute Lethal Total-body Gamma Radiation.","authors":"Alana D Carpenter, Issa Melendez-Miranda, Yaoxiang Li, Jeyalakshmi Kandhavelu, Oluseyi O Fatanmi, Stephen Y Wise, Amrita K Cheema, Vijay K Singh","doi":"10.1667/RADE-25-00029.1","DOIUrl":"10.1667/RADE-25-00029.1","url":null,"abstract":"<p><p>Ionizing radiation exposure induces cellular and molecular damage, leading to a chain of events that results in tissue and organ injury. Proteomics studies help identify, validate, and quantify alterations in protein abundance downstream of radiation-induced genomic changes. The current study strives to characterize and validate the proteomic changes at the preterminal stage (moribund animals) in serum samples collected from rhesus macaques lethally and acutely irradiated with two different doses of cobalt-60 gamma-radiation. Peripheral blood samples were collected prior to exposure, after exposure, and at the preterminal stage from nonhuman primates (NHPs) that did not survive after 7.2 or 7.6 Gy total-body irradiation (LD60-80/60). Using mass spectrometry-based proteomics, we analyzed samples collected at various time points after irradiation. Our findings revealed that radiation induced significant time-dependent proteomic alterations compared to pre-exposure samples. More pronounced dysregulation in pathways related to immune response and hemostasis, specifically platelet function, was present in preterminal samples, suggesting that alterations in these pathways may indicate the preterminal phenotype. These results offer important insights for the identification and validation of biomarkers for radiation-induced lethality that would be of great importance for triage during a radiological/nuclear mass casualty event.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"59-74"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026267","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}
D L Preston, L Y Krestinina, D O Stram, S B Epifanova, E A Shishkina, B A Napier, B E Moroz, N V Startsev, M O Degteva, A V Akleyev
{"title":"Radiation Dose and Solid Cancer Mortality Risk in the Techa River and East Urals Radioactive Trace Cohorts in 1950-2016.","authors":"D L Preston, L Y Krestinina, D O Stram, S B Epifanova, E A Shishkina, B A Napier, B E Moroz, N V Startsev, M O Degteva, A V Akleyev","doi":"10.1667/RADE-24-00195.1","DOIUrl":"10.1667/RADE-24-00195.1","url":null,"abstract":"<p><p>The objective of the work was to estimate the dose dependence of mortality risk from solid cancers in a cohort that includes members of two cohorts of residents of the Southern Urals who received chronic environmental low-dose, low-dose-rate radiation exposure from releases of the Mayak Plutonium Production Association. These analyses use dose and dose uncertainty estimates from a recently developed Monte-Carlo dosimetry system. The 47,950 members of the cohort include the Techa River Cohort of people who lived in the villages on the Techa River between 1950 and the end of 1960 and the East Urals Radioactive Trace Cohort of people who lived in territories of Chelyabinsk Oblast contaminated by the explosion of a radioactive waste depository on September 29, 1957, between the date of the accident and the end of 1959. As of the end of 2016, there were 25,723 deaths, including 3,783 solid cancer deaths, with 1,392,394 person years among non-migrant cohort members. The solid cancer mortality rate dose response adjusted for the effect of smoking was estimated using an excess relative risk model. Parameter estimates and confidence intervals were computed using maximum likelihood methods. The corrected information matrix method was used to determine risk estimate confidence intervals (CI) adjusted for dose uncertainty using information on the statistical uncertainty of the parameter estimates and individual dose uncertainty information provided by the dosimetry system. The smoking-adjusted linear excess relative risk (ERR) per 100 mGy for solid cancer mortality was 0.060 (95% CI 0.018 to 0.108) at age 70. The ERR increased significantly in proportion to age to the power 3.1 (95% CI 0.44 to 6.4). The joint effect of radiation and smoking on solid cancer rates appeared to be multiplicative. Adjustment for smoking had little impact on the estimated ERR. Adjusting the ERR confidence interval for dose uncertainty slightly increased the upper confidence bound (adjusted 95% CI 0.018 to 0.120). There was no evidence of nonlinearity in the solid cancer dose response. Except for liver cancer, ERR estimates for various specific types of cancer were positive. However, they were statistically significant only for stomach and female breast cancers. Statistically significant smoking effects were seen for cancers of the lung, stomach, and esophagus. Risk estimates for the two groups in the cohort did not differ significantly. The risk estimates in this cohort were consistent with data in two major occupational cohorts, they were higher than those seen in the Mayak Worker Cohort. While the ERR estimates at age 70 are like those seen in the atomic bomb survivor life span study, the ERR age dependencies were strikingly different. These findings strengthen the evidence for low-dose, low-dose-rate radiation effects on solid cancer mortality rates.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"15-26"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151519","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}