{"title":"Harnessing Senescence for Antitumor Immunity to Advance Cancer Treatment.","authors":"Pataje G S Prasanna","doi":"10.1667/RADE-24-00098.1","DOIUrl":"10.1667/RADE-24-00098.1","url":null,"abstract":"<p><p>Considering the limitations and complexities of the cell-killing-based cancer treatment approaches, one could aim to integrate symbiotic advances in many energy delivery technologies and transformational pieces of evidence in research on senescence and immunomodulators to advance cancer treatment. Although senescent cells contribute to drug tolerance, resistance to therapy, tumorigenesis, maladapting cancer phenotypes, tumor relapse, recurrence, and metastasis, emerging pieces of evidence also demonstrate that acutely induced senescent cells in tumors can elicit a strong and lasting antitumor immune response juxtaposed to the immunologically silent apoptotic cells. This commentary is to help develop an unconventional conceptual framework to advance cancer treatment. Accordingly, it will involve transiently inducing senescent cells in tumors at optimal levels to prime the immune system with radiation, then eliminating senescent cells with senolytics (drugs that specifically eliminate senescent cells) to disrupt their positive feedback accumulation (to prevent tumor maladaptation and adverse effects in healthy cells) and unleash long-lasting antitumor immunity with immunomodulators. The approach is reasonably speculative and will require scientifically rigorous \"fit-for-purpose,\" well-controlled preclinical research and development involving dose and schedule optimization of radiation and drugs, using representative in vitro and in vivo cancer models to obtain high-quality data to proceed to clinical studies.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"727-733"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081411","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}
Jessica A Stering, Amy E Biggs, Tara E Carney, Megan E Oest, Brittany A Simone
{"title":"Caloric Restriction Diet Attenuates Systemic Bone Fragility after Radiotherapy.","authors":"Jessica A Stering, Amy E Biggs, Tara E Carney, Megan E Oest, Brittany A Simone","doi":"10.1667/RADE-23-00227.1","DOIUrl":"10.1667/RADE-23-00227.1","url":null,"abstract":"<p><p>Bone fragility is a well-documented long-term side effect of radiotherapy, which currently has no preventative treatments. In this study, we applied a caloric restriction (CR) diet to attenuate both local and systemic bone loss after irradiation (RTx) in an established female Balb/c mouse model (4 consecutive daily doses of 5 Gy to the right hindlimb only). CR mice were tapered down to a 30% reduced calorie diet (RTx/CR) one week before irradiation, while regular diet (RD) mice received food ad libitum (RTx/RD). Unirradiated (sham) mice received either a 30% CR diet (SH/CR) or received food ad libitum (SH/RD). Irradiated, contralateral, and unirradiated hindlimbs were evaluated at 2, 4, and 8 weeks postirradiation using micro-computed tomography (μCT) to assess bone morphology and 3-point bending to quantify femur strength. Histological analysis of irradiated and unirradiated tibiae was performed to examine general bone tissue cytology and serum biomarker analysis was performed using terminal blood draw samples. After treatment, femur strength and metaphyseal bone quantity was decreased in irradiated and contralateral femora of RTx/RD mice compared to SH/RD femurs; this finding is consistent with previous studies. RTx/CR mice had positive effects when compared to RTx/RD mice, including increased strength relative to body mass in both the irradiated and contralateral limb, increased trabecular bone mass, and decreased marrow adiposity. However, a number of adverse effects were also observed, including a significant decrease in body mass and decreased cortical bone. Overall, CR shows promise as a preventative treatment for postirradiated bone fragility, yet questions remain to be addressed in future studies. Ideal diet duration, impact to normal tissue, and mechanism of action must be explored to better understand the clinical implication of a CR diet.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"765-774"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294082","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":"Disulfiram Upgrades the Radiosensitivity of Osteosarcoma by Enhancing Apoptosis and P53-Induced Cell Cycle Arrest.","authors":"Qiujian Lian, Fengmei Chen, Zhilin Sha, Haonan Zhao, Jingyan Li, Tongjiang Chen, Chang Liu, Bingxuan Wang, Zhiwei Wang, Suchi Qiao","doi":"10.1667/RADE-24-00046.1","DOIUrl":"10.1667/RADE-24-00046.1","url":null,"abstract":"<p><p>The prognosis of osteosarcoma has not been improved for decades. As radioresistance is one of the major reasons, effective radiotherapy sensitization drugs need to be discovered. HOS and K7M2 osteosarcoma cell lines were treated with disulfiram (DSF) and radiation to assess cell viability, proliferation, migration ability, apoptosis level, ROS and Ca2+ level, and cell cycle in vitro. A HOS-derived subcutaneous tumor mouse model was constructed to evaluate tumor growth after DSF combined with radiation, and the Tunel assay and immunohistochemistry of Ki67 were conducted. Western blot was used to evaluate the protein expression level. The IC50 and working concentration of DSF in osteosarcoma cell lines were ascertained. When combined with radiation, DSF effectively suppressed cell viability, proliferation, and migration, while enhancing apoptosis in osteosarcoma cells. The cell cycle postirradiation exhibited a downward shift in the G1 phase, but the addition of DSF counteracted this trend. The combination of DSF and radiation exhibited inhibitory effects on tumor growth in vivo, which was corroborated by Ki67 staining and Tunel assay. Western blot analysis revealed that DSF upregulated the expression of P53, P21, CDKN2C, BAX, and cleaved Caspase-3 while downregulating BCL2, CDK4/6, and CyclinD1 after irradiation. Our results document that DSF exerts its radiosensitization effects in vivo and in vitro, and is a valuable radiosensitizing drug option for osteosarcoma. The radiosensitization effect is mainly achieved by activating the apoptotic pathway and promoting cell cycle arrest induced by P53/P21 and CDKN2C after irradiation.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"752-764"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294083","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}
Qiu Wang, Binyan Cao, Junwei Zhan, Xinyu Hu, Yang Yu, Xueyu Li, Ying Liu
{"title":"Sea Buckthorn Oil Promotes the PI3K-Akt-ERK Signaling Pathway and Macrophage M2 Polarization to Reduce Radiation-induced Skin Injury.","authors":"Qiu Wang, Binyan Cao, Junwei Zhan, Xinyu Hu, Yang Yu, Xueyu Li, Ying Liu","doi":"10.1667/RADE-23-00100.1","DOIUrl":"10.1667/RADE-23-00100.1","url":null,"abstract":"<p><p>In this work, we explored the role and mechanism of sea buckthorn oil in reducing radiation-induced skin damage. The radiation-induced rat skin injury model was established using strontium-90. Rats were treated with sea buckthorn oil twice a day postirradiation, and skin damage was observed at different times and evaluated using an injury score. Skin pathological changes were observed using hematoxylin and eosin (H&E) staining. Western blotting and immunohistochemistry were used to detect the expression of vascular growth and pathway proteins. ELISA was used to detect the secretion level of inflammatory factors. Immunohistochemistry was used to detect macrophage polarization marker proteins. We found that sea buckthorn oil can alleviate radiation-induced skin damage, accelerate skin vascular regeneration, and promote the up-regulation of vascular endothelial growth factor (VEGF) and its receptor (VEGFR). These results demonstrate the beneficial effects of sea buckthorn oil on radiation-induced skin damage. Furthermore, the levels of IL-1β and TNF-α in the sea buckthorn oil treatment group were significantly lower than those in the control group, while the levels of IL-4 and IL10 were significantly higher (P < 0.05). CD206 expression also increased in the sea buckthorn oil treatment group, while CD16 expression decreased compared to the control group (P < 0.05). Western blotting showed that PI3K, Akt and ERK expression increased in the sea buckthorn oil treatment group (P < 0.05). The beneficial effect of sea buckthorn oil in reducing the inflammatory response in irradiated rats was diminished when they were treated with PI3K inhibitor. We conclude that sea buckthorn oil may regulate macrophage M2 polarization by increasing the PI3K-Akt-ERK signaling pathway, thereby inhibiting the inflammatory response and promoting skin vascular regeneration to prevent and treat radiation-induced skin damage.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"785-794"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352749","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}
Alizeh Z Khan, Cheyanne M Scholl, Joshua G Henry, Parminder S Basran
{"title":"A Comparative Study on Radiosensitivity of Canine Osteosarcoma Cell Lines Subjected to Spatially Fractionated Radiotherapy.","authors":"Alizeh Z Khan, Cheyanne M Scholl, Joshua G Henry, Parminder S Basran","doi":"10.1667/RADE-24-00168.1","DOIUrl":"10.1667/RADE-24-00168.1","url":null,"abstract":"<p><p>Canine appendicular osteosarcoma (OSCA) is a highly aggressive cancer, constituting 85% of all bone tumors in dogs, predominantly affecting larger breeds and exhibiting a high metastatic rate. This disease also shares many genomic similarities with human osteosarcomas, making it an ideal comparative model for treatment discovery. In this study, we characterized the radiobiological properties of several OSCA cell lines when subjected to spatially fractionated radiation therapy (SFRT) and chemotherapy. Specifically, we focused on lower (peak) doses from SFRT ranging from 1 to 10 Gy. These canine OSCA cell lines serve as useful models for osteosarcoma research that can be utilized to find translational treatments for both canine and human patients. This study reaffirms established clinical wisdom regarding the notoriously radioresistant profile of osteosarcomas but additionally offers compelling evidence supporting SFRT as a promising treatment option that could be used in conjunction with other cytotoxic agents.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"745-751"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294081","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}
Sobia Zareen, Sajid Bashir, Aamir Shahzad, Muhammad Kashif, Guogang Ren
{"title":"Direct and Indirect Effects for Radiosensitization of Gold Nanoparticles in Proton Therapy.","authors":"Sobia Zareen, Sajid Bashir, Aamir Shahzad, Muhammad Kashif, Guogang Ren","doi":"10.1667/RADE-23-00199.1","DOIUrl":"10.1667/RADE-23-00199.1","url":null,"abstract":"<p><p>The radiosensitization characteristics of gold nanoparticles (GNPs) have been investigated in a single cell irradiated with monoenergetic beams of protons of various energies using TOPAS-nBio, an advanced toolkit of TOPAS. Both direct and indirect effects against single-strand breaks (SSBs) are investigated and their double-strand breaks (DSBs) have been calculated. A single spherical cell interaction with a detailed DNA structure has been modeled and simulated under different conditions such as particle sizes and concentrations of GNPs, their biodistributions and associated proton energies. The physical interaction among protons, suspension water and GNPs has been simulated using a dual physics approach, while the interaction between water radiolysis and OH radicals was considered in the chemical process to save computational time. The present simulations involve irradiating the cell geometry with a dose of 1 Gy. The range of DSBs (Gy-1 Gbp-1) obtained was 2.1 ± 0.09 to 21.74 ± 0.4 for all GNPs of sizes 6-50 nm the proton energies in the range of 5-50 MeV. Regardless of proton energy and GNP size, the calculations showed that the contribution of indirect and hybrid DSBs remains higher in all simulation types than that of direct DSBs. New simulation outcomes of the indirect DSBs illustrate a percentage increase, while we cannot get an increase in the direct and hybrid DSBs in most cases when compared with no GNPs cases. The indirect DSBs provide the highest enhancement factor of 1.89 at 30 nm GNPs in size for 30 MeV protons energy, and the direct and hybrid DSBs indicate a slight increase in enhancement. The work indicates that the use of GNPs increased indirect DNA DSBs, while hybrid DSBs show only a slight increase in enhancement, and no enhancement is shown in direct DNA DSBs. It is significant to consider other mechanisms such as DNA damage repair when investigating DNA damage.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"795-806"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473389","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}
Sophie R Finkelstein, Rutulkumar Patel, Katherine Deland, Joshua Mercer, Bryce Starr, Daniel Zhu, Hooney Min, Michael Reinsvold, Lorraine Da Silva Campos, Nerissa T Williams, Lixia Luo, Yan Ma, Jadee Neff, Mark J Hoenerhoff, Everett J Moding, David G Kirsch
{"title":"56Fe-ion Exposure Increases the Incidence of Lung and Brain Tumors at a Similar Rate in Male and Female Mice.","authors":"Sophie R Finkelstein, Rutulkumar Patel, Katherine Deland, Joshua Mercer, Bryce Starr, Daniel Zhu, Hooney Min, Michael Reinsvold, Lorraine Da Silva Campos, Nerissa T Williams, Lixia Luo, Yan Ma, Jadee Neff, Mark J Hoenerhoff, Everett J Moding, David G Kirsch","doi":"10.1667/RADE-24-00004.1","DOIUrl":"10.1667/RADE-24-00004.1","url":null,"abstract":"<p><p>The main deterrent to long-term space travel is the risk of Radiation Exposure Induced Death (REID). The National Aeronautics and Space Administration (NASA) has adopted Permissible Exposure Levels (PELs) to limit the probability of REID to 3% for the risk of death due to radiation-induced carcinogenesis. The most significant contributor to current REID estimates for astronauts is the risk of lung cancer. Recently updated lung cancer estimates from Japan's atomic bomb survivors showed that the excess relative risk of lung cancer by age 70 is roughly fourfold higher in females compared to males. However, whether sex differences may impact the risk of lung cancer due to exposure to high charge and energy (HZE) radiation is not well studied. Thus, to evaluate the impact of sex differences on the risk of solid cancer development after HZE radiation exposure, we irradiated Rbfl/fl, Trp53fl/+ male and female mice infected with Adeno-Cre with various doses of 320 kVp X rays or 600 MeV/n 56Fe ions and monitored them for any radiation-induced malignancies. We conducted complete necropsy and histopathology of major organs on 183 male and 157 female mice after following them for 350 days postirradiation. We observed that lung adenomas/carcinomas and esthesioneuroblastomas (ENBs) were the most common primary malignancies in mice exposed to X rays and 56Fe ions, respectively. In addition, 1 Gy 56Fe-ion exposure compared to X-ray exposure led to a significantly increased incidence of lung adenomas/carcinomas (P = 0.02) and ENBs (P < 0.0001) in mice. However, we did not find a significantly higher incidence of any solid malignancies in female mice as compared to male mice, regardless of radiation quality. Furthermore, gene expression analysis of ENBs suggested a distinct gene expression pattern with similar hallmark pathways altered, such as MYC targets and MTORC1 signaling, in ENBs induced by X rays and 56Fe ions. Thus, our data revealed that 56Fe-ion exposure significantly accelerated the development of lung adenomas/carcinomas and ENBs compared to X rays, but the rate of solid malignancies was similar between male and female mice, regardless of radiation quality.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"734-744"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294080","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":"RPS15 Coordinates with CtIP to Facilitate Homologous Recombination and Confer Therapeutic Resistance in Breast Cancer.","authors":"Baohang Lin, Guan Huang, Zishan Yuan, Xun Peng, Chunliang Yu, Jialu Zheng, Zequn Li, Juanyun Li, Jinan Liang, Bo Xu","doi":"10.1667/RADE-24-00134.1","DOIUrl":"10.1667/RADE-24-00134.1","url":null,"abstract":"<p><p>The repair of DNA double-strand breaks (DSBs) through homologous recombination (HR) is vital for maintaining the stability and integrity of the genome. RNA binding proteins (RBPs) intricately regulate the DNA damage repair process, yet the precise molecular mechanisms underlying their function remain incompletely understood. In this study, we highlight the pivotal role of RPS15, a representative RBP, in homologous recombination repair. Specifically, we demonstrate that RPS15 promotes DNA end resection, a crucial step in homologous recombination. Notably, we identify an interaction between RPS15 and CtIP, a key factor in homologous recombination repair. This interaction is essential for CtIP recruitment to DSB sites, subsequent RPA coating, and RAD51 replacement, all critical steps in efficient homologous recombination repair and conferring resistance to genotoxic treatments. Functionally, suppressing RPS15 expression sensitizes cancer cells to X-ray radiation and enhances the therapeutic synergistic effect of PARP1 inhibitors in breast cancer cells. In summary, our findings reveal that RPS15 promotes DNA end resection to ensure effective homologous recombination repair, suggesting its potential as a therapeutic target in cancer treatment.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"775-784"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366360","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":"Radiosensitivity-related Variation in MicroRNA-34a-5p Levels and Subsequent Neuronal Loss in the Hilus of the Dentate Gyrus after Irradiation at Postnatal Days 10 and 21 in Mice.","authors":"Lian Liu, Hong Wang, Zhao Wu Ma, Feng Ru Tang","doi":"10.1667/RADE-23-00248.1","DOIUrl":"10.1667/RADE-23-00248.1","url":null,"abstract":"<p><p>The radiosensitivity of mice differs between postnatal days 10 (P10) and 21(P21); these days mark different stages of brain development. In the present study, Ki67 and doublecotin (DCX) immunostaining and hematoxylin staining was performed, which showed that acute radiation exposure at postnatal day 10 induced higher cell apoptosis and loss in the hilus of the dentate gyrus at day 1 postirradiation than postnatal day 21. MicroRNA (miRNA) sequencing and real-time quantitative reverse transcription PCR (qRT-PCR) analysis indicated the upregulation of miRNA-34a-5p at days 1 and 7 after irradiation at postnatal day 10, but not at postnatal day 21. Down-regulation of T-cell intracytoplasmic antigen-1 pathway (Tia1) was indicated by qRT-PCR at day 1 day but not day 7 after irradiation at postnatal day 10. Neurobehavioral testing in mature mice irradiated at postnatal day 10 demonstrated the impairment of short-term memory in novel object recognition and spatial memory, compared to those irradiated at postnatal day 21. Combined with our previous luciferase assay showing the direct interaction of miRNA34a-5p and Tia1, these findings suggest that radiation-induced abnormal miR-34a-5p/Tial interaction at day 1 after irradiation at postnatal day 10 may be involved in apoptosis of the dentate gyrus hilar, impairment of neurogenesis and subsequent short-term memory loss as observed in the novel object recognition and Barnes maze tests.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"677-684"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009329","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}
Vladimir Drozdovitch, Victor Kryuchkov, Elena Bakhanova, Petro Bondarenko, Konstantin Chizhov, Ivan Golovanov, Vadim Chumak
{"title":"Dose Reconstruction for Epidemiological Studies among Ukrainian Chernobyl Cleanup Workers.","authors":"Vladimir Drozdovitch, Victor Kryuchkov, Elena Bakhanova, Petro Bondarenko, Konstantin Chizhov, Ivan Golovanov, Vadim Chumak","doi":"10.1667/RADE-23-00117.1","DOIUrl":"10.1667/RADE-23-00117.1","url":null,"abstract":"<p><p>The present paper provides an overview of the methods and summarizes the results of estimating radiation doses and their uncertainties for Ukrainian-American epidemiological studies among the Chernobyl (Chornobyl) cleanup workers. After the Chernobyl accident occurred on April 26, 1986, more than 300,000 Ukrainian cleanup workers took part between 1986 and 1990 in decontamination and recovery activities at the site of the Chernobyl Nuclear Power Plant. The U.S. National Cancer Institute in collaboration with the Ukrainian National Research Center for Radiation Medicine conducted several epidemiological studies in this population. An important part of these studies was the reconstruction of the study participants' radiation doses and the assessment of uncertainties in doses. A method called realistic analytical dose reconstruction with uncertainty estimation (RADRUE) was used to calculate the doses from external irradiation during cleanup missions, which was the main exposure pathway for most study participants. At the initial phase of the accident during the atmospheric releases of radioactivity from the destroyed reactor, the cleanup workers also received doses from inhalation of radionuclides. In addition, study participants received doses at their places of residence, especially those who lived in highly contaminated areas. The radiation doses estimated for 2,048 male cleanup workers included in the Ukrainian-American epidemiological studies varied widely: (i) bone-marrow doses from external irradiation in the case-control study of leukemia of 1,000 cleanup workers ranged from 3.7 × 10-5 mGy to 3.3 Gy (mean = 92 mGy); (ii) thyroid doses in the case-control study of thyroid cancer in 607 persons from all exposure pathways combined were from 0.15 mGy to 9.0 Gy (mean = 199 mGy); (iii) gonadal doses in 183 cleanup workers from all exposure pathways combined in the study of germline mutations in the offspring after parental irradiation (trio study) ranged from 0.58 mGy to 4.1 Gy (mean = 392 mGy); (iv) thyroid doses in the human factor uncertainties study among 47 persons were from 20 mGy to 2.1 Gy (mean = 295 mGy); and (v) lung doses in the study of germline genetic variants associated with host susceptibility to COVID-19 estimated for 211 cleanup workers were from 0.024 mGy to 2.5 Gy (mean = 249 mGy). Doses of female cleanup workers were much lower than those of male cleanup workers: the mean doses for female cleanup workers were 27 mGy for 34 women included in the trio study and 56 mGy for 48 women participated in the study of germline genetic variants associated with host susceptibility to COVID-19. Uncertainties in dose estimates included two components: (i) inherent uncertainties arising from the stochastic random variability of the parameters used in exposure assessment and from a lack of knowledge about the true values of the parameters; and (ii) human factor uncertainties due to poor memory recall resulting in incomplete, inaccurate, ","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"626-638"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983121","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}