Ya Heng, Feifei Wang, Zhonghui Zhang, Zebang Lin, Dahai Zhao, Qiuling Li
{"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}
Huiting Peng, Bingqing Cui, Jianming Wei, Min Yuan, Wenjuan Liu, Jing Shi, Yuguo Liu
{"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}
Peiquan Liu, Min Fu, Dong Liu, Tengfei Chao, Jiaxuan Zhang
{"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":"https://doi.org/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":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-26","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":"Synthesis and Evaluation of Novel 18F-labeled Oxadiazole-based Positron Emission Tomography Tracers for β-Amyloid.","authors":"Zhongyuan Qi, Wantong Guo, Mengchao Cui, Jie Lu","doi":"10.1667/RADE-25-00035.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00035.1","url":null,"abstract":"<p><p>This research details the synthesis, structure-activity evaluation, and analysis of novel oxadiazole-based compounds for visualizing β-amyloid (Aβ) in Alzheimer's disease (AD). The derivatives exhibited binding affinities to Aβ aggregates in vitro. The [18F]-labeled compounds, [18F]4-(5-(4-Fluorophenyl)-1,3,4-oxadiazol-2-yl)-N, N-dimethylaniline (compound [18F] 3) and [18F] 4-(5-(4-Fluorophenyl)-1,3,4-oxadiazol-2-yl)-N-methylaniline (compound [18F]4), effectively labeled Aβ plaques in brain sections from Alzheimer's disease patients and APP/PS1 mice. In dynamic positron emission tomography (PET) studies on healthy mice, these compounds demonstrated favorable brain uptake followed by clearance. Additional structural alterations to compounds [18F] 3 and [18F] 4 may lead to the development of more efficient PET tracers for precise visualization of Aβ plaques.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693168","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}
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
{"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":"https://doi.org/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":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-21","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}
Ellen E Quillen, George W Schaaf, Jamie N Justice, Gregory O Dugan, Brendan Johnson, Colin Reed, John D Olson, J Mark Cline
{"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}
Brendan J Johnson, Rachel N Andrews, John D Olson, J Mark Cline
{"title":"Radiation-induced Brain Injury and the Radiation Late Effects Cohort (RLEC) of Rhesus Macaques (Macaca mulatta).","authors":"Brendan J Johnson, Rachel N Andrews, John D Olson, J Mark Cline","doi":"10.1667/RADE-24-00033.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00033.1","url":null,"abstract":"<p><p>In the event of a nuclear accident or attack, thousands of people could receive high doses of total-body irradiation (TBI). Although retrospective analyses of atomic bomb and nuclear disaster survivors have been conducted, the long-term outcomes on the brain and cognitive function are conflicting. Radiation-induced brain injury (RIBI) is characterized by inflammation, vascular injury, deficits in neuronal function, and white matter (WM) injury, but the molecular mechanisms by which this occurs remain unknown. Animal models are crucial for evaluating radiation effects on the brain and have provided significant insight into the pathogenesis of RIBI. Rodents are the most commonly utilized animal models in radiation research, and much has been gleaned from these animals. Non-human primates (NHPs) are the closest genetically, anatomically, and physiologically to humans and therefore represent a valuable resource in translational neuroscience. NHPs have been utilized in radiation studies for several decades and continue to be important models of RIBI, yet few studies have evaluated the long-term impact of radiation on neurocognitive function. The Radiation Late Effects Cohort (RLEC) is a group of rhesus macaques dedicated to evaluating the long-term effects of TBI on multiple systems, including the nervous system. Studies have demonstrated that animals within the RLEC manifest shared patterns of injury between macaques and humans after fractionated whole-brain irradiation (WBI), including vascular injury, neuroinflammation, and WM injury. While pathological outcomes in late-delayed RIBI have been well characterized, studies evaluating the functional outcomes in NHPs are scarce, highlighting the need for future studies. Correlating relevant structural and functional outcomes are critical for identifying targets involved in the pathogenesis of injury. Much information has been gleaned from animal studies of RIBI, and NHPs, particularly those in the RLEC will continue to be valuable models in translational neuroscience.</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":"143586668","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}
Jingyun Lee, Xiaofei Chen, Katherine M Fanning, Catherine Si, Ashley T Davis, David H Wasserman, Deanna Bracy, Cristina M Furdui, Kylie Kavanagh
{"title":"Persistent Postirradiation Skeletal Muscle Protein and Insulin Sensitivity Changes in Nonhuman Primates.","authors":"Jingyun Lee, Xiaofei Chen, Katherine M Fanning, Catherine Si, Ashley T Davis, David H Wasserman, Deanna Bracy, Cristina M Furdui, Kylie Kavanagh","doi":"10.1667/RADE-23-00223.1","DOIUrl":"https://doi.org/10.1667/RADE-23-00223.1","url":null,"abstract":"<p><p>Increased incidence of diabetes has been reported after whole-body irradiation in cancer survivors and in the years after exposure in research studies of nonhuman primates. Type 2 diabetes presents in the absence of obesity and suggests that skeletal muscle, the predominant organ responsible for minute-to-minute glucose disposal, is persistently dysfunctional. We evaluated skeletal muscle (SkM) from control (CTL, n = 8) and irradiated (IRRAD, n = 16) male rhesus macaques (Macaca mulatta) that had been exposed to an average whole-body dose of 6.5 Gy after an average of 4 years of follow-up. Irradiated animals had deficient SkM basal and insulin-stimulated receptor activation that was unrelated to histologically assessed fiber size, extracellular matrix and endothelial components. Protein extracted from irradiated muscle showed that Akt2, downstream of insulin receptor activation, was sulfenyl-modified and thus a target for radiation-related glycemic dysregulation. Shotgun proteomics identified upregulation of many mitochondrial and peroxisome-associated proteins, and increases were confirmed by immunoblotting of select protein targets. Proteomic pathway enrichment mapping showed distinct protein clustering between CTL and IRRAD groups. Mitochondrial proteins were surveyed and confirm that mitochondrial turnover may be increased after irradiation with higher fission and fusion markers. The results indicate that irradiated muscle is persistently insulin resistant, with evidence of intracellular protein oxidation and shifts in mitochondrial dynamics and function.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575822","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}
Erica L Stover, Michelle L Rock, John D Olson, George W Schaaf, Thomas H Oguin, J Mark Cline, Andrew N Macintyre
{"title":"The Long-term Effects of Acute Total-Body Irradiation on Pre-irradiation Measles-vaccine-induced Immunological Memory.","authors":"Erica L Stover, Michelle L Rock, John D Olson, George W Schaaf, Thomas H Oguin, J Mark Cline, Andrew N Macintyre","doi":"10.1667/RADE-23-00203.1","DOIUrl":"https://doi.org/10.1667/RADE-23-00203.1","url":null,"abstract":"<p><p>Acute total-body irradiation (TBI) leads to transient dose-dependent lymphopenia. While lymphocyte numbers gradually recover, there remain subtle but long-lasting changes to B and T cell populations years after radiation exposure. The degree to which immunological memory is retained after TBI is unknown; however, it is conceivable that vaccine-induced protective immunity is jeopardized. To test this hypothesis, samples were collected from a cohort of rhesus macaques that were vaccinated against measles virus, irradiated, and then allowed to recover from the acute radiation effects for at least a year. Animals received 0 to 7.5 Gy TBI or 10 Gy with 5% bone marrow shielding. Plasma from 109 animals were evaluated for measles-binding antibodies and the ability to neutralize live measles virus. Females exhibited higher measles binding and neutralizing titers, and irradiated animals of both sexes exhibited significant radiation-dose dependent reductions in measles binding IgG and neutralizing titers. Peripheral blood mononuclear cells (PBMC) from the vaccinated, irradiated animals were then stimulated in vitro with measles antigens to evaluate cellular responses. No radiation-dose effects on CD8 T cell responses to measles antigens were detected. In contrast, PBMC from vaccinated, irradiated males exhibited radiation dose-dependent reductions in the percentages of CD4 T cells expressing activation-associated markers and cytokines in response to measles antigens. There were also significant dose- or dose/sex-interacting effects on the levels of IP10, MIP1β, and IL-6 present in the antigen-stimulated PBMC cultures. Cells from animals receiving 10 Gy with 5% bone marrow shielding exhibited signs of T-cell anergy. PBMC from females exhibited only weak responses to measles antigen stimulation regardless of radiation exposure. Collectively, these in vitro studies indicate that radiation can cause protracted dose- and sex-dependent damage to established humoral and cellular immunological memories of measles.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573707","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}