Radiation research最新文献

{"title":"Developing an RNA Signature for Radiation Injury Using a Human Liver-on-a-Chip Model.","authors":"Shannon Martello, Yuki Ueda, Michelle A Bylicky, Jonathan Pinney, Juan Dalo, Kevin M K Scott, Molykutty J Aryankalayil, C Norman Coleman","doi":"10.1667/RADE-24-00047.1","DOIUrl":"10.1667/RADE-24-00047.1","url":null,"abstract":"<p><p>Radiation exposure in a therapeutic setting or during a mass casualty event requires improved medical triaging, where the time to delivery and quantity of medical countermeasures are critical to survival. Radiation-induced liver injury (RILI) and fibrosis can lead to death, but clinical symptoms manifest late in disease pathogenesis and there is no simple diagnostic test to determine RILI. Because animal models do not completely recapitulate clinical symptoms, we used a human liver-on-a-chip model to identify biomarkers of RILI. The goals of this study were: 1. to establish a microfluidic liver-on-a-chip device as a physiologically relevant model for studying radiation-induced tissue damage; and 2. to determine acute changes in RNA expression and biological pathway regulation that identify potential biomarkers and mechanisms of RILI. To model functional human liver tissue, we used the Emulate organ-on-a-chip system to establish a co-culture of human liver sinusoidal endothelial cells (LSECs) and hepatocytes. The chips were subject to 0 Gy (sham), 1 Gy, 4 Gy, or 10 Gy irradiation and cells were collected at 6 h, 24 h, or 7 days postirradiation for RNA isolation. To identify significant expression changes in messenger RNA (mRNA) and long non-coding RNA (lncRNA), we performed RNA sequencing (RNASeq) to conduct whole transcriptome analysis. We found distinct differences in expression patterns by time, dose, and cell type, with higher doses of radiation resulting in the most pronounced expression changes, as anticipated. Ingenuity Pathway Analysis indicated significant inhibition of the cell viability pathway 24 h after 10 Gy exposure in LSECs but activation of this pathway in hepatocytes, highlighting differences between cell types despite receiving the same radiation dose. Overall, hepatocytes showed fewer gene expression changes in response to radiation, with only 3 statistically significant differentially expressed genes at 7 days: APOBEC3H, PTCHD4, and GDNF. We further highlight lncRNA of interest including DINO and PURPL in hepatocytes and TMPO-AS1 and PRC-AS1 in LSECs, identifying potential biomarkers of RILI. We demonstrated the potential utility of a human liver-on-a-chip model with primary cells to model organ-specific radiation injury, establishing a model for radiation medical countermeasure development and further biomarker validation. Furthermore, we identified biomarkers that differentiate radiation dose and defined cell-specific targets for potential radiation mitigation therapies.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875782","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":"Mitigating Viral Impact on the Radiation Response of the Lung.","authors":"Angela M Groves, Nicole D Paris, Carl J Johnston, Eric Hernady, Jacob Finkelstein, Paige Lawrence, Brian Marples","doi":"10.1667/RADE-24-00103.1","DOIUrl":"10.1667/RADE-24-00103.1","url":null,"abstract":"<p><p>Inflammation is a key factor in both influenza and radiation-induced lung pathophysiology. This implies a commonality of response to pulmonary damage from these insults and suggests exacerbated pathology may occur after combined exposure. We therefore tested the hypothesis that past inflammation from viral infection alters the lung microenvironment and lowers tolerance for radiation injury. Mice were inoculated with influenza A virus (IAV) and three weeks later, after virus clearance, mice received total-body irradiation (TBI). Survival as well as systemic and local lung inflammation were assessed, and strategies to mitigate pulmonary injury were investigated. After IAV infection alone, body condition recovered within 3 weeks, however inflammatory pathways remained active for 15 weeks. IAV infection exacerbated subsequent TBI responses, evident by increased lethality, enhanced histologically evident lung injury and an altered lung macrophage phenotype. To mitigate this enhanced sensitivity, captopril [an angiotensin converting enzyme inhibitor (ACEi)] was administered to limit tissue inflammation, or inflammatory monocyte-derived macrophage recruitment was blocked with a C-C chemokine receptor type 2 (CCR2) inhibitor. Both treatments abrogated the changes in circulating immune cells observed 4 weeks after TBI, and attenuated pro-inflammatory phenotypes in lung alveolar macrophages, appearing to shift immune cell dynamics towards recovery. Histologically apparent lung injury was not improved by either treatment. We show that latent lung injury from viral infection exacerbates radiation morbidity and mortality. Although strategies that attenuate proinflammatory immune cell phenotypes can normalize macrophage dynamics, this does not fully mitigate lung injury. Recognizing that past viral infections can enhance lung radiosensitivity is of critical importance for patients receiving TBI, as it could increase the incidence of adverse outcomes.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760621","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":"Bertram \"Bert\" Walter Maidment Jr., PhD (1947-2024).","authors":"Andrea L DiCarlo, Carmen I Rios, Lanyn P Taliaferro, Merriline M Satyamitra, David R Cassatt, Daniel Rotrosen","doi":"10.1667/RADE-24-00BWM.a","DOIUrl":"https://doi.org/10.1667/RADE-24-00BWM.a","url":null,"abstract":"","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154889","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":"A Call for Curriculum Development to Prepare Medical Students and Residents to Assist with Mass Casualties after a Catastrophic Radiological or Nuclear Incident.","authors":"Joseph R Dynlacht, Paul M Wallach, Thomas Chenworth, Daniel J Blumenthal","doi":"10.1667/RADE-23-000259.1","DOIUrl":"https://doi.org/10.1667/RADE-23-000259.1","url":null,"abstract":"","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154888","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":"Selecting the Most Relevant Mouse Strains for Evaluating Radiation-Induced Multiple Tissue Injury after Leg-Shielded Partial-Body Gamma Irradiation.","authors":"Julian D Down, Milton R Cornwall-Brady, Wei Huang, Martina Hurwitz, Scott R Floyd, Omer H Yilmaz","doi":"10.1667/RADE-24-00058.1","DOIUrl":"10.1667/RADE-24-00058.1","url":null,"abstract":"<p><p>Animal studies are needed that best simulate a large-scale, inhomogeneous body exposure after a radiological or nuclear incident and that provides a platform for future development of medical countermeasures. A partial-body irradiation (PBI) model using 137Cs gamma rays with hind limb (tibia) shielding was developed and assessed for the sequalae of radiation injuries to gastrointestinal tract, bone marrow (BM) and lung and among different genetic mouse strains (C57BL/6J, C57L/J, CBA/J and FVB/NJ). In this case, a marginal level of BM shielding (∼2%) provided adequate protection against lethality from infection and hemorrhage and enabled escalation of radiation doses with evaluation of both acute and delayed radiation syndromes. A steep radiation dose-dependent body weight loss was observed over the first 5 days attributed to enteritis with C57BL/6J mice appearing to be the most sensitive strain. Peripheral blood cell analysis revealed significant depression and recovery of leukocytes and platelets over the first month after PBI and were comparable among the four different mouse strains. Latent pulmonary injury was observed on micro-CT imaging at 4 months in C57L/J mice and confirmed histologically as severe pneumonitis that was lethal at 12 Gy. The lethality and radiological densitometry (HUs) dose responses were comparable to previous studies on C57L/J mice after total-body irradiation (TBI) and BM transplant rescue as well as after localized whole-thorax irradiation (WTI). Indeed, the lethal radiation doses and latency appeared similar for pneumonitis appearing in rhesus macaques after WTI or PBI as well as predicted for patients given systemic radiotherapy. In contrast, PBI treatment of C57BL/6 mice at a higher dose of 14 Gy had far longer survival times and developed extreme and debilitating pIeural effusions; an anomaly as similarly reported in previous thorax irradiation studies on this mouse strain. In summary, a radiation exposure model that delivers PBI to unanesthetized mice in a device that provides consistent shielding of the hind limb BM was developed for 137Cs gamma rays with physical characteristics and relevance to relatively high photon energies expected from the detonation of a nuclear device or accidental release of ionizing radiation. Standard strains such as C57BL/6J mice may be used reliably for early GI or hematological radiation syndromes while the C57L/J mouse strain stands out as the most appropriate for evaluating the delayed pulmonary effects of acute radiation exposure and recapitulating this disease in humans.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767150","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":"Biomarkers for Radiation Biodosimetry and Correlation with Hematopoietic Injury in a Humanized Mouse Model.","authors":"Qi Wang, Bezalel A Bacon, Maria Taveras, Michelle A Phillippi, Xuefeng Wu, Constantinos G Broustas, Igor Shuryak, Helen C Turner","doi":"10.1667/RADE-24-00049.1","DOIUrl":"10.1667/RADE-24-00049.1","url":null,"abstract":"<p><p>After a large-scale radiological or nuclear event, hundreds of thousands of people may be exposed to ionizing radiation and require subsequent medical management. Acute exposure to moderate doses (2-6 Gy) of radiation can lead to the hematopoietic acute radiation syndrome, in which the bone marrow (BM) is severely compromised, and severe hemorrhage and infection are common. Previously, we have developed a panel of intracellular protein markers (FDXR, ACTN1, DDB2, BAX, p53 and TSPYL2), designed to reconstruct absorbed radiation dose from human peripheral blood (PB) leukocyte samples in humanized mice up to 3 days after exposure. The objective of this work was to continue to use the humanized mouse model to evaluate biomarker dose-/time- kinetics in human PB leukocytes in vivo, at an earlier (day 2) and later (day 7) time point, after exposure to total-body irradiation (TBI) doses of 0 to 2 Gy of X rays. In addition, to assess hematological sensitivity and radiation-induced injury, PB leukocyte cell counts, human BM hematopoietic stem cell (HSC) and progenitor cell [multipotent progenitor (MPP), common myeloid progenitor (CMP), granulocyte myeloid progenitor (GMP), megakaryocyte/erythrocyte progenitor (MEP) and multi-lymphoid progenitor (MLP)] levels were measured, and their correlation was also examined as the BM damages are difficult to assess by routine tests. Peripheral blood B-cells were significantly lower after TBI doses of 0.5 Gy on day 2 and 2 Gy on days 2 and 7; T-cells were significantly reduced only on day 2 after 2 Gy TBI. Bone marrow HSCs and MPP cells showed a dose-dependent depletion after irradiation with 0.5 Gy and 2 Gy on day 2, and after 1 Gy and 2 Gy on day 7. Circulating B cells correlated with HSCs, MPP and MLP cells on day 2, whereas T cells correlated with MPP, and myeloid cells correlated with MLP cells. On day 7, B cells correlated with MPP, CMP, GMP and MEP, while myeloid cells correlated with CMP, GMP and MEP. The intracellular leukocyte biomarkers were able to discriminate unirradiated and irradiated samples at different time points calculated by receiver operating characteristic (ROC) curve. Using machine learning algorithm methods, combining ACTN1, p53, TSPYL2 and PB-T cell and PB-B cell counts served as a strong predictor (area under the ROC >0.8) to distinguish unirradiated and irradiated samples independent of the days after TBI. The results further validated our biomarker-based triage assay and additionally evaluated the radiation sensitivity of the hematopoietic system after TBI exposures.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734869","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":"Relative Biological Effectiveness of Carbon Ion Beams for Induction of Medulloblastoma with Radiation-specific Chromosome 13 Deletion in Ptch1+/- Mice.","authors":"Chizuru Tsuruoka, Mayumi Shinagawa, Yi Shang, Yoshiko Amasaki, Masaaki Sunaoshi, Tatsuhiko Imaoka, Takamitsu Morioka, Yoshiya Shimada, Shizuko Kakinuma","doi":"10.1667/RADE-23-00229.1","DOIUrl":"10.1667/RADE-23-00229.1","url":null,"abstract":"<p><p>Carbon ion radiotherapy (CIRT) for pediatric cancer is currently limited because of the unknown risk of induction of secondary cancers. Medulloblastoma of Ptch1+/- mice offers a unique experimental system for radiation-induced carcinogenesis, in which tumors are classified into spontaneous and radiation-induced subtypes based on their features of loss of heterozygosity (LOH) that affect the wild-type Ptch1 allele. The present study aims to investigate in young Ptch1+/- mice the carcinogenic effect, and its age dependence, of the low-linear energy transfer (LET, ∼13 keV/µm) carbon ions, to which normal tissues in front of the tumor are exposed during therapy. We irradiated Ptch1+/- mice at postnatal day (P) 1, 4, or 10 with 290 MeV/u carbon ions (0.05-0.5 Gy; LET, 13 keV/µm) and monitored them for medulloblastoma development. Loss of heterozygosity of seven genetic markers on chromosome 13 (where Ptch1 resides) was studied to classify the tumors. Carbon ion exposure induced medulloblastoma most effectively at P1. The LOH patterns of tumors were either telomeric or interstitial, the latter occurring almost exclusively in the irradiated groups, allowing the use of interstitial LOH as a biomarker of radiation-induced tumors. Radiation-induced tumors developed during a narrow age window (most strongly at P1 and only moderately at P4, with suppressed tumorigenesis at P10). Calculated using previous results using 137Cs gamma rays, the values for relative biological effectiveness (RBE) regarding radiation-induced tumors were 4.1 (3.4, 4.8) and 4.3 (3.3, 5.2) (mean and 95% confidence interval) for exposure at P1 and 4, respectively. Thus, the RBE of carbon ions for medulloblastoma induction in Ptch1+/- mice was higher than the generally recognized RBE of 1-2 for cell killing, chromosome aberrations, and skin reactions.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760622","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":"Estimating Impacts of p16 Status on Tumor Radiosensitivity in Head and Neck Cancer using Predictive Models.","authors":"Atsushi Kaida, Hitomi Nojima, Masahiko Miura","doi":"10.1667/RADE-24-00066.1","DOIUrl":"10.1667/RADE-24-00066.1","url":null,"abstract":"<p><p>The intrinsic radiosensitivity index (RSI) and genomic-adjusted radiation dose (GARD) were reported to be able to predict the surviving fraction at 2 Gy and therapeutic effect when delivering actual treatment doses using the gene expression profiles of clinical cases. Given the impact of p16 status, a surrogate marker of the human papillomavirus (HPV) infection, on radiosensitivity, we attempted to apply the RSI and GARD to estimate p16-associated radiosensitivity in head and neck squamous cell carcinoma (HNSC). For this purpose, The Cancer Genome Atlas (TCGA) dataset was employed. In the GARD calculation, we assumed that p16-positive patients received 60 Gy in 30 fractions, while p16-negative patients received 70 Gy in 35 fractions. p16 positivity was associated with favorable characteristics compared to negative patients. The RSI and GARD analyses demonstrated increased radiosensitivity and high therapeutic effect in p16-positive patients, compared to p16-negative patients. Additionally, tumor microenvironmental conditions predicted by other models were also significantly affected by p16 status. Collectively, the models used in this study could be a promising tool for estimating p16-associated radiosensitivity in HNSC.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734870","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":"The Central Role of Cytogenetics in Radiation Biology.","authors":"Susan M Bailey, Stephen R Kunkel, Joel S Bedford, Michael N Cornforth","doi":"10.1667/RADE-24-00038.1","DOIUrl":"10.1667/RADE-24-00038.1","url":null,"abstract":"<p><p>Radiation cytogenetics has a rich history seldom appreciated by those outside the field. Early radiobiology was dominated by physics and biophysical concepts that borrowed heavily from the study of radiation-induced chromosome aberrations. From such studies, quantitative relationships between biological effect and changes in absorbed dose, dose rate and ionization density were codified into key concepts of radiobiological theory that have persisted for nearly a century. This review aims to provide a historical perspective of some of these concepts, including evidence supporting the contention that chromosome aberrations underlie development of many, if not most, of the biological effects of concern for humans exposed to ionizing radiations including cancer induction, on the one hand, and tumor eradication on the other. The significance of discoveries originating from these studies has widened and extended far beyond their original scope. Chromosome structural rearrangements viewed in mitotic cells were first attributed to the production of breaks by the radiations during interphase, followed by the rejoining or mis-rejoining among ends of other nearby breaks. These relatively modest beginnings eventually led to the discovery and characterization of DNA repair of double-strand breaks by non-homologous end joining, whose importance to various biological processes is now widely appreciated. Two examples, among many, are V(D)J recombination and speciation. Rapid technological advancements in cytogenetics, the burgeoning fields of molecular radiobiology and third-generation sequencing served as a point of confluence between the old and new. As a result, the emergent field of \"cytogenomics\" now becomes uniquely positioned for the purpose of more fully understanding mechanisms underlying the biological effects of ionizing radiation exposure.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564178","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":"EGO to ECO: Tracing the History of Radioecology from the 1950's to the Present Day.","authors":"Bruno F E Matarèse, Rhea Desai, Deborah H Oughton, Carmel Mothersill","doi":"10.1667/RADE-24-00035.1","DOIUrl":"10.1667/RADE-24-00035.1","url":null,"abstract":"<p><p>This paper starts with a brief history of the birth of the field of radioecology during the Cold War with a focus on US activity. We review the establishment of the international system for radiation protection and the science underlying the guidelines. We then discuss the famous ICRP 60 statement that if \"Man\" is protected, so is everything else and show how this led to a focus in radioecology on pathways to \"Man\" rather than concern about impacts on environments or ecosystems. We then review the contributions of Radiation Research Society members and papers published in Radiation Research which contributed to the knowledge base about effects on non-human species. These fed into international databases and computer-based tools such as ERICA and ResRad Biota to guide regulators. We then examine the origins of the concern that ICRP 60 is not sufficient to protect ecosystems and discuss the establishment of ICRP Committee 5 and its recommendations to establish reference animals and plants. The review finishes with current concerns that reference animals and plants (RAPs) are not sufficient to protect ecosystems, given the complexity of interacting factors such as the climate emergency and discusses the efforts of ICRP, the International Union of Radioecologists and other bodies to capture the concepts of ecosystem services and ecosystem complexity modelling in radioecology.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634331","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}