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Direct and Indirect Effects for Radiosensitization of Gold Nanoparticles in Proton Therapy. 质子疗法中金纳米粒子放射增敏的直接和间接效应
IF 2.5 3区 医学
Radiation research Pub Date : 2024-11-01 DOI: 10.1667/RADE-23-00199.1
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}
引用次数: 0
56Fe-ion Exposure Increases the Incidence of Lung and Brain Tumors at a Similar Rate in Male and Female Mice. 雌雄小鼠暴露于 56Fe 离子会以相似的速度增加肺癌和脑瘤的发病率。
IF 2.5 3区 医学
Radiation research Pub Date : 2024-11-01 DOI: 10.1667/RADE-24-00004.1
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}
引用次数: 0
RPS15 Coordinates with CtIP to Facilitate Homologous Recombination and Confer Therapeutic Resistance in Breast Cancer. RPS15 与 CtIP 相互配合,促进同源重组并增强乳腺癌的治疗抵抗力
IF 2.5 3区 医学
Radiation research Pub Date : 2024-11-01 DOI: 10.1667/RADE-24-00134.1
Baohang Lin, Guan Huang, Zishan Yuan, Xun Peng, Chunliang Yu, Jialu Zheng, Zequn Li, Juanyun Li, Jinan Liang, Bo Xu
{"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}
引用次数: 0
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. 小鼠出生后第 10 天和第 21 天受到辐照后齿状回脊髓中与辐射敏感性相关的 MicroRNA-34a-5p 水平变化及随后的神经元丢失。
IF 2.5 3区 医学
Radiation research Pub Date : 2024-10-01 DOI: 10.1667/RADE-23-00248.1
Lian Liu, Hong Wang, Zhao Wu Ma, Feng Ru Tang
{"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}
引用次数: 0
Risks of Circulatory Diseases among Korean Radiation Workers Exposed to Low-dose Radiation. 暴露于低剂量辐射的韩国辐射工人患循环系统疾病的风险。
IF 2.5 3区 医学
Radiation research Pub Date : 2024-10-01 DOI: 10.1667/RADE-23-00148.1
Eun Shil Cha, Dalnim Lee, Hyoju Sung, Won Il Jang, Tae-Eun Kwon, Ho Yeon Jeong, Songwon Seo
{"title":"Risks of Circulatory Diseases among Korean Radiation Workers Exposed to Low-dose Radiation.","authors":"Eun Shil Cha, Dalnim Lee, Hyoju Sung, Won Il Jang, Tae-Eun Kwon, Ho Yeon Jeong, Songwon Seo","doi":"10.1667/RADE-23-00148.1","DOIUrl":"10.1667/RADE-23-00148.1","url":null,"abstract":"<p><p>High-dose radiation has been widely recognized as a risk factor for circulatory diseases. There is increasing evidence for risk of circulatory diseases in response to low and moderate radiation doses in recent years, but the results are not always consistent. We aimed to evaluate the associations between low-dose radiation exposure (<0.1 Gy) and the incidence of circulatory disease in a large cohort of Korean radiation workers. We collected data from a cohort of 187,001 radiation workers monitored for personal radiation dose since 1984 and linked with the National Health Insurance Service data from 2002 to 2021. Excess relative risks (ERRs) per 100 mGy were calculated to quantify the radiation dose-response relationship. The mean duration of follow-up was 13.3 years. A total of 12,705 cases of cerebrovascular disease (CeVD) and 19,647 cases of ischemic heart disease (IHD) were diagnosed during the follow-up period (2002-2021). The average cumulative heart dose was 4.10 mGy, ranging from 0 to 992.62 mGy. The ERR per 100 mGy with 10-year lagged cumulative heart doses was estimated at -0.094 (95% CI -0.248, 0.070) for CeVD and -0.173 (95% CI -0.299, -0.041) for IHD. The ERRs were not significantly changed after adjusting for confounding factors such as smoking, income, blood pressure, body mass index, and blood glucose level. A linear quadratic model was found to provide a better fit for the ERR of CeVD and IHD than a linear model (P = 0.009 and 0.030, respectively). There were no statistically significant variations in ERR/100 mGy estimates for either CeVD or IHD in terms of sex, attained age, and duration of employment; however, heterogeneity in the ERR/100 mGy estimates for CeVD among occupations was observed (P = 0.001). Our study did not find conclusive evidence supporting the association between occupational low-dose radiation and an increased risk of circulatory diseases. The significant negative ERR estimates for IHD need further investigation with a more extended follow-up period.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"649-661"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988712","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}
引用次数: 0
Dose Reconstruction for Epidemiological Studies among Ukrainian Chernobyl Cleanup Workers. 乌克兰切尔诺贝利清理工人流行病学研究的剂量重建。
IF 2.5 3区 医学
Radiation research Pub Date : 2024-10-01 DOI: 10.1667/RADE-23-00117.1
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":"&lt;p&gt;&lt;p&gt;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}
引用次数: 0
Dimethyl Sulfoxide Attenuates Ionizing Radiation-induced Centrosome Overduplication and Multipolar Cell Division in Human Induced Pluripotent Stem Cells. 二甲基亚砜可减轻电离辐射诱导的人类诱导多能干细胞中心体过度复制和多极细胞分裂。
IF 2.5 3区 医学
Radiation research Pub Date : 2024-10-01 DOI: 10.1667/RADE-24-00069.1
Mikio Shimada, Ryoichi Hirayama, Yoshihisa Matsumoto
{"title":"Dimethyl Sulfoxide Attenuates Ionizing Radiation-induced Centrosome Overduplication and Multipolar Cell Division in Human Induced Pluripotent Stem Cells.","authors":"Mikio Shimada, Ryoichi Hirayama, Yoshihisa Matsumoto","doi":"10.1667/RADE-24-00069.1","DOIUrl":"10.1667/RADE-24-00069.1","url":null,"abstract":"<p><p>Centrosomes are important organelles for cell division and genome stability. Ionizing radiation exposure efficiently induces centrosome overduplication via the disconnection of the cell and centrosome duplication cycles. Over duplicated centrosomes cause mitotic catastrophe or chromosome aberrations, leading to cell death or tumorigenesis. Pluripotent stem cells, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), can differentiate into all organs. To maintain pluripotency, PSCs show specific cellular dynamics, such as a short G1 phase and silenced cell-cycle checkpoints for high cellular proliferation. However, how exogenous DNA damage affects cell cycle-dependent centrosome number regulation in PSCs remains unknown. This study used human iPSCs (hiPSCs) derived from primary skin fibroblasts as a PSC model to address this question. hiPSCs derived from somatic cells could be a useful tool for addressing the radiation response in cell lineage differentiation. After radiation exposure, the hiPSCs showed a higher frequency of centrosome overduplication and multipolar cell division than the differentiated cells. To suppress the indirect effect of radiation exposure, we used the radical scavenger dimethyl sulfoxide (DMSO). Combined treatment with radiation and DMSO efficiently suppressed DNA damage and centrosome overduplication in hiPSCs. Our results will contribute to the understanding of the dynamics of stem cells and the assessment of the risk of genome instability for regenerative medicine.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"719-725"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111408","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}
引用次数: 0
The Role of Natural Background Radiation in Maintaining Genomic Stability in the CGL1 Human Hybrid Model System. 自然本底辐射在维持 CGL1 人类杂交模型系统基因组稳定性中的作用》(The Role of Natural Background Radiation in Maintaining Genomic Stability in the CGL1 Human Hybrid Model System)。
IF 2.5 3区 医学
Radiation research Pub Date : 2024-10-01 DOI: 10.1667/RADE-23-00243.1
Jake Pirkkanen, Taylor Laframboise, Jayden Peterson, Alyssa Labelle, Forest Mahoney, Michel Lapointe, Marc S Mendonca, T C Tai, Simon J Lees, Sujeenthar Tharmalingam, Douglas R Boreham, Christopher Thome
{"title":"The Role of Natural Background Radiation in Maintaining Genomic Stability in the CGL1 Human Hybrid Model System.","authors":"Jake Pirkkanen, Taylor Laframboise, Jayden Peterson, Alyssa Labelle, Forest Mahoney, Michel Lapointe, Marc S Mendonca, T C Tai, Simon J Lees, Sujeenthar Tharmalingam, Douglas R Boreham, Christopher Thome","doi":"10.1667/RADE-23-00243.1","DOIUrl":"10.1667/RADE-23-00243.1","url":null,"abstract":"<p><p>Natural background ionizing radiation is present on the earth's surface; however, the biological role of this chronic low-dose-rate exposure remains unknown. The Researching the Effects of the Presence and Absence of Ionizing Radiation (REPAIR) project is examining the impacts of sub-natural background radiation exposure through experiments conducted 2 km underground in SNOLAB. The rock overburden combined with experiment-specific shielding provides a background radiation dose rate 30 times lower than on the surface. We hypothesize that natural background radiation is essential for life and maintains genomic stability and that prolonged exposure to sub-background environments will be detrimental to biological systems. To evaluate this, human hybrid CGL1 cells were continuously cultured in SNOLAB and our surface control laboratory for 16 weeks. Cells were assayed every 4 weeks for growth rate, alkaline phosphatase (ALP) activity (a marker of cellular transformation in the CGL1 system), and the expression of genes related to DNA damage and cell cycle regulation. A subset of cells was also exposed to a challenge radiation dose (0.1 to 8 Gy of X rays) and assayed for clonogenic survival and DNA double-strand break induction to examine if prolonged sub-background exposure alters the cellular response to high-dose irradiation. At each 4-week time point, sub-background radiation exposure did not significantly alter cell growth rates, survival, DNA damage, or gene expression. However, cells cultured in SNOLAB showed significantly higher ALP activity, a marker of carcinogenesis in these cells, which increased with longer exposure to the sub-background environment, indicative of neoplastic progression. Overall, these data suggest that sub-background radiation exposure does not impact growth, survival, or DNA damage in CGL1 cells but may lead to increased rates of neoplastic transformation, highlighting a potentially important role for natural background radiation in maintaining normal cellular function and genomic stability.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"617-625"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971784","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}
引用次数: 0
Organ-specific Biodosimetry Modeling Using Proteomic Biomarkers of Radiation Exposure. 利用辐照的蛋白质组生物标志物建立器官特异性生物模拟模型
IF 2.5 3区 医学
Radiation research Pub Date : 2024-10-01 DOI: 10.1667/RADE-24-00092.1
M Sproull, Y Fan, Q Chen, D Meerzaman, K Camphausen
{"title":"Organ-specific Biodosimetry Modeling Using Proteomic Biomarkers of Radiation Exposure.","authors":"M Sproull, Y Fan, Q Chen, D Meerzaman, K Camphausen","doi":"10.1667/RADE-24-00092.1","DOIUrl":"10.1667/RADE-24-00092.1","url":null,"abstract":"<p><p>In future mass casualty medical management scenarios involving radiation injury, medical diagnostics to both identify those who have been exposed and the level of exposure will be needed. As almost all exposures in the field are heterogeneous, determination of degree of exposure and which vital organs have been exposed will be essential for effective medical management. In the current study we sought to characterize novel proteomic biomarkers of radiation exposure and develop exposure and dose prediction algorithms for a variety of exposure paradigms to include uniform total-body exposures, and organ-specific partial-body exposures to only the brain, only the gut and only the lung. C57BL6 female mice received a single total-body irradiation (TBI) of 2, 4 or 8 Gy, 2 and 8 Gy for lung or gut exposures, and 2, 8 or 16 Gy for exposure to only the brain. Plasma was then screened using the SomaScan v4.1 assay for ∼7,000 protein analytes. A subset panel of protein biomarkers demonstrating significant (FDR<0.05 and |logFC|>0.2) changes in expression after radiation exposure was characterized. All proteins were used for feature selection to build 7 different predictive models of radiation exposure using different sample cohort combinations. These models were structured according to practical field considerations to differentiate level of exposure, in addition to identification of organ-specific exposures. Each model algorithm built using a unique sample cohort was validated with a training set of samples and tested with a separate new sample series. The overall predictive accuracy for all models was 100% at the model training level. When tested with reserved samples Model 1 which compared an \"exposure\" group inclusive of all TBI and organ-specific partial-body exposures in the study vs. control, and Model 2 which differentiated between control, TBI and partials (all organ-specific partial-body exposures) the resulting prediction accuracy was 92.3% and 95.4%, respectively. For identification of organ-specific exposures vs. control, Model 3 (only brain), Model 4 (only gut) and Model 5 (only lung) were developed with predictive accuracies of 78.3%, 88.9% and 94.4%, respectively. Finally, for Models 6 and 7, which differentiated between TBI and separate organ-specific partial-body cohorts, the testing predictive accuracy was 83.1% and 92.3%, respectively. These models represent novel predictive panels of radiation responsive proteomic biomarkers and illustrate the feasibility of development of biodosimetry algorithms with utility for simultaneous classification of total-body, partial-body and organ-specific radiation exposures.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"697-705"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120468","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}
引用次数: 0
Long Non-Coding RNA PVT1 Facilitates Radiation-Induced Vascular Endothelial Cell Injury through Sponging MicroRNA-9-5p. 长非编码 RNA PVT1 通过疏导 MicroRNA-9-5p 促进辐射诱导的血管内皮细胞损伤
IF 2.5 3区 医学
Radiation research Pub Date : 2024-10-01 DOI: 10.1667/RADE-24-00089.1
Jing Wang, Yanting Zhang, Wei Lian, Min Gan
{"title":"Long Non-Coding RNA PVT1 Facilitates Radiation-Induced Vascular Endothelial Cell Injury through Sponging MicroRNA-9-5p.","authors":"Jing Wang, Yanting Zhang, Wei Lian, Min Gan","doi":"10.1667/RADE-24-00089.1","DOIUrl":"10.1667/RADE-24-00089.1","url":null,"abstract":"<p><p>Radiotherapy is a common therapeutic strategy for various solid tumors, with vascular endothelial injury being a common side effect. The study aimed to examine the effect of long non-coding RNA PVT1 on radiation-induced vascular endothelial cell injury, and explore the possible underlying mechanism. Human umbilical vein endothelial cells (HUVECs) were exposed to different doses of X ray to mimic radiation. LncRNA and miRNA levels were detected via qRT-PCR. Interaction between lncRNA and miRNAs was determined through dual-luciferase reporter assay. Statistical processing was conducted using student's t test between two groups and one-way ANOVA among multiple groups, and P < 0.05 means a significant difference. GO and KEGG were performed for the function and pathway enrichment analysis. LncRNA PVT1 elevated along with the increase of radiation dose in HUVECs. Poorly expressed lncRNA PVT1 promotes cell viability and inhibits oxidative stress. PVT1 serves as a competitive endogenous RNA (ceRNA) of miR-9-5p. miR-9-5p inhibitor inverted the influence of PVT1 knockdown on radiation-stimulated cell apoptosis and oxidative stress in HUVECs. KEGG analysis identified significant enrichment of the MAPK signaling pathway among overlapping target genes of miR-9-5p. LncRNA PVT1 knockdown alleviated radiation-induced vascular endothelial injury via sponging miR-9-5p. The underlying mechanism might be probably MAPK signaling-related.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"670-676"},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983122","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}
引用次数: 0
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