Radiation research最新文献

{"title":"Modelling Cellular Response to Ionizing Radiation: Mechanistic, Semi-Mechanistic, and Phenomenological Approaches - A Historical Perspective.","authors":"Reza Taleei, Shirin Rahmanian, Hooshang Nikjoo","doi":"10.1667/RADE-24-00019.1","DOIUrl":"10.1667/RADE-24-00019.1","url":null,"abstract":"<p><p>Radiation research is a multidisciplinary field, and among its many branches, mathematical and computational modelers have played a significant role in advancing boundaries of knowledge. A fundamental contribution is modelling cellular response to ionizing radiation as that is the key to not only understanding how radiation can kill cancer cells, but also cause cancer and other health issues. The invention of microdosimetry in the 1950s by Harold Rossi paved the way for brilliant scientists to study the mechanism of radiation at cellular and sub-cellular scales. This paper reviews some snippets of ingenious mathematical and computational models published in microdosimetry symposium proceedings and publications of the radiation research community. Among these are simulations of radiation tracks at atomic and molecular levels using Monte Carlo methods, models of cell survival, quantification of the amount of energy required to create a single strand break, and models of DNA-damage-repair. These models can broadly be categorized into mechanistic, semi-mechanistic, and phenomenological approaches, and this review seeks to provide historical context of their development. We salute pioneers of the field and great teachers who supported and educated the younger members of the community and showed them how to build upon their work.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"143-160"},"PeriodicalIF":2.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446804","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":"Revisiting the Historic Strontium-90 Ingestion Beagle Study Conducted at the University of California Davis: Opportunity in Archival Materials.","authors":"Alexander D Glasco, Lori A Snyder, Tatjana Paunesku, Sara C Howard, David A Hooper, Ashley P Golden, Gayle E Woloschak","doi":"10.1667/RADE-24-000022.1","DOIUrl":"10.1667/RADE-24-000022.1","url":null,"abstract":"<p><p>Strontium-90 is a radionuclide found in high concentrations in nuclear reactor waste and nuclear fallout from reactor accidents and atomic bomb explosions. In the 1950s, little was known regarding the health consequences of strontium-90 internalization. To assess the health effects of strontium-90 ingestion in infancy through adolescence, the Atomic Energy Commission and Department of Energy funded large-scale beagle studies at the University of California Davis. Conducted from 1956 to 1989, the strontium-90 ingestion study followed roughly 460 beagles throughout their lifespans after they were exposed to strontium-90 in utero (through feeding of the mother) and fed strontium-90 feed at varying doses from weaning to age 540 days. The extensive medical data and formalin-fixed paraffin-embedded tissues were transferred from UC Davis to the National Radiobiology Archive in 1992 and subsequently to the Northwestern University Radiobiology Archive in 2010. Here, we summarize the design of the strontium-90 ingestion study and give an overview of its most frequent recorded findings. As shown before, radiation-associated neoplasias (osteosarcoma, myeloproliferative syndrome and select squamous cell carcinomas) were almost exclusively observed in the highest dose groups, while the incidence of neoplasias most frequent in controls decreased as dose increased. The occurrence of congestive heart failure in each dose group, not previously assessed by UC Davis researchers, showed a non-significant increase between the controls and lower dose groups that may have been significant had sample sizes been larger. Detailed secondary analyses of these data and samples may uncover health endpoints that were not evaluated by the team that conducted the study.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"289-308"},"PeriodicalIF":2.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451376","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":"Clustered DNA Damage and its Complexity: Tracking the History.","authors":"Dudley T Goodhead, Michael Weinfeld","doi":"10.1667/RADE-24-00017.1","DOIUrl":"10.1667/RADE-24-00017.1","url":null,"abstract":"<p><p>The concept of radiation-induced clustered damage in DNA has grown over the past several decades to become a topic of considerable interest across the scientific disciplines involved in studies of the biological effects of ionizing radiation. This paper, prepared for the 70th anniversary issue of Radiation Research, traces historical development of the three main threads of physics, chemistry, and biochemical/cellular responses that led to the hypothesis and demonstration that a key component of the biological effectiveness of ionizing radiation is its characteristic of producing clustered DNA damage of varying complexities. The physics thread has roots that started as early as the 1920s, grew to identify critical nanometre-scale clusterings of ionizations relevant to biological effectiveness, and then, by the turn of the century, had produced an extensive array of quantitative predictions on the complexity of clustered DNA damage from different radiations. Monte Carlo track structure simulation techniques played a key role through these developments, and they are now incorporated into many recent and ongoing studies modelling the effects of radiation. The chemistry thread was seeded by water-radiolysis descriptions of events in water as radical-containing \"spurs,\" demonstration of the important role of the hydroxyl radical in radiation-inactivation of cells and the difficulty of protection by radical scavengers. This led to the concept and description of locally multiply damaged sites (LMDS) for DNA double-strand breaks and other combinations of DNA base damage and strand breakage that could arise from a spur overlapping, or created in very close proximity to, the DNA. In these ways, both the physics and the chemistry threads, largely in parallel, put out the challenge to the experimental research community to verify these predictions of clustered DNA damage from ionizing radiations and to investigate their relevance to DNA repair and subsequent cellular effects. The third thread, biochemical and cell-based research, responded strongly to the challenge by demonstrating the existence and biological importance of clustered DNA damage. Investigations have included repair of a wide variety of defined constructs of clustered damage, evaluation of mutagenic consequences, identification of clustered base-damage within irradiated cells, and identification of co-localization of repair complexes indicative of complex clustered damage after high-LET irradiation, as well as extensive studies of the repair pathways involved in repair of simple double-strand breaks. There remains, however, a great deal more to be learned because of the diversity of clustered DNA damage and of the biological responses.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"385-407"},"PeriodicalIF":2.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493224","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 Historical Survey of Key Epidemiological Studies of Ionizing Radiation Exposure.","authors":"Mark P Little, Dimitry Bazyka, Amy Berrington de Gonzalez, Alina V Brenner, Vadim V Chumak, Harry M Cullings, Robert D Daniels, Benjamin French, Eric Grant, Nobuyuki Hamada, Michael Hauptmann, Gerald M Kendall, Dominique Laurier, Choonsik Lee, Won Jin Lee, Martha S Linet, Kiyohiko Mabuchi, Lindsay M Morton, Colin R Muirhead, Dale L Preston, Preetha Rajaraman, David B Richardson, Ritsu Sakata, Jonathan M Samet, Steven L Simon, Hiromi Sugiyama, Richard Wakeford, Lydia B Zablotska","doi":"10.1667/RADE-24-00021.1","DOIUrl":"10.1667/RADE-24-00021.1","url":null,"abstract":"<p><p>In this article we review the history of key epidemiological studies of populations exposed to ionizing radiation. We highlight historical and recent findings regarding radiation-associated risks for incidence and mortality of cancer and non-cancer outcomes with emphasis on study design and methods of exposure assessment and dose estimation along with brief consideration of sources of bias for a few of the more important studies. We examine the findings from the epidemiological studies of the Japanese atomic bomb survivors, persons exposed to radiation for diagnostic or therapeutic purposes, those exposed to environmental sources including Chornobyl and other reactor accidents, and occupationally exposed cohorts. We also summarize results of pooled studies. These summaries are necessarily brief, but we provide references to more detailed information. We discuss possible future directions of study, to include assessment of susceptible populations, and possible new populations, data sources, study designs and methods of analysis.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"432-487"},"PeriodicalIF":2.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634330","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":"Biology of Exfoliation of Plasma Membrane-Derived Vesicles and the Radiation Response: Historical Background, Applications in Biodosimetry and Cell-Free Therapeutics, and Quantal Mechanisms for Their Release and Function with Implications for Space Travel.","authors":"Nicholas Dainiak","doi":"10.1667/RADE-24-00078.1","DOIUrl":"10.1667/RADE-24-00078.1","url":null,"abstract":"<p><p>This historical review of extracellular vesicles in the setting of exposure to ionizing radiation (IR) traces our understanding of how vesicles were initially examined and reported in the literature in the late 1970s (for secreted exosomes) and early 1980s (for plasma membrane-derived, exfoliated vesicles) to where we are now and where we may be headed in the next decade. An emphasis is placed on biophysical properties of extracellular vesicles, energy consumption and the role of vesiculation as an essential component of membrane turnover. The impact of intercellular signal trafficking by vesicle surface and intra-vesicular lipids, proteins, nucleic acids and metabolites is reviewed in the context of biomarkers for estimating individual radiation dose after exposure to radiation, pathogenesis of disease and development of cell-free therapeutics. Since vesicles express both growth stimulatory and inhibitory molecules, a hypothesis is proposed to consider superposition in a shared space and entanglement of molecules by energy sources that are external to human cells. Implications of this approach for travel in deep space are briefly discussed in the context of clinical disorders that have been observed after space travel.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"328-354"},"PeriodicalIF":2.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564177","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":"Seventy Years of Dose-response Models: From the Target Theory to the Use of Big Databases Involving Cell Survival and DNA Repair.","authors":"Larry Bodgi, Laurent Pujo-Menjouet, Audrey Bouchet, Michel Bourguignon, Nicolas Foray","doi":"10.1667/RADE-24-00015.1","DOIUrl":"10.1667/RADE-24-00015.1","url":null,"abstract":"<p><p>Radiobiological data, whether obtained at the clinical, biological or molecular level has significantly contributed to a better description and prediction of the individual dose-response to ionizing radiation and a better estimation of the radiation-induced risks. Particularly, over the last seventy years, the amount of radiobiological data has considerably increased, and permitted the mathematical formulas describing dose-response to become less empirical. A better understanding of the basic radiobiological mechanisms has also contributed to establish quantitative inter-correlations between clinical, biological and molecular biomarkers, refining again the mathematical models of description. Today, big data approaches and, more recently, artificial intelligence may finally complete and secure this long process of thinking from the multi-scale description of radiation-induced events to their prediction. Here, we reviewed the major dose-response models applied in radiobiology for quantifying molecular and cellular radiosensitivity and aimed to explain their evolution: Specifically, we highlighted the advances concerning the target theory with the cell survival models and the progressive introduction of the DNA repair process in the mathematical models. Furthermore, we described how the technological advances have changed the description of DNA double-strand break (DSB) repair kinetics by introducing the important notion of DSB recognition, independent of that of DSB repair. Initially developed separately, target theory on one hand and, DSB recognition and repair, on the other hand may be now fused into a unified model involving the cascade of phosphorylations mediated by the ATM kinase in response to any genotoxic stress.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"130-142"},"PeriodicalIF":2.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158015","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":"Evaluation of Cell Cycle-Dependent Migration Activity after X-ray Exposure: A Radiobiological Approach for Optimization of Radiotherapy with Cell Cycle-Targeting Agents.","authors":"Ryosuke Seino, Hisanori Fukunaga","doi":"10.1667/RADE-23-00213.1","DOIUrl":"10.1667/RADE-23-00213.1","url":null,"abstract":"<p><p>Radiotherapy with cell cycle-specific anticancer agents has become an important option in the control of both primary tumors and metastases. Here, we used image analysis algorithms that enable quick segmentation and tracking to describe a radiobiological approach for the optimized selection of cell cycle-targeting anticancer drugs for radiotherapy. We confirmed cell cycle-synchronization using human cervical cancer HeLa cells expressing a fluorescent ubiquitination-based cell cycle indicator (FUCCI) as a cell cycle-monitoring probe. Cells synchronized in the G1 and G2 phases were irradiated with X rays at 0.5-2 Gy. Each cell was identified using Cellpose, a deep learning-based algorithm for cellular segmentation, and the velocity and direction of migration were analyzed using the TrackMate plugin in Fiji ImageJ. G1 phase synchronized cells showed a dose-dependent decrease in velocity after irradiation, while G2 cells tended to increase their velocity. The migration pattern of all cells appeared to be a random walk model, regardless of the exposure dose. In addition, we used cisplatin to arrest the cell cycle. HeLa-FUCCI cells arrested at the G2 phase via cisplatin treatment showed enhanced cell migration after X-ray exposure. These results indicated that anticancer agents that arrest the cell cycle of cancer cells in a specific phase may enhance cell migration after radiotherapy. Our approach, using cellular segmentation and tracking algorithms, could enhance the radiobiological assessment of cell cycle-specific migration after irradiation to aid in optimizing radiotherapy using cell cycle-targeting agents.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"87-95"},"PeriodicalIF":2.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892389","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":"Pharmacokinetic and Metabolomic Studies with a Promising Radiation Countermeasure, BBT-059 (PEGylated interleukin-11), in Rhesus Nonhuman Primates.","authors":"Alana D Carpenter, Yaoxiang Li, Stephen Y Wise, Oluseyi O Fatanmi, Sarah A Petrus, Christine M Fam, Sharon J Carlson, George N Cox, Amrita K Cheema, Vijay K Singh","doi":"10.1667/RADE-23-00194.1","DOIUrl":"10.1667/RADE-23-00194.1","url":null,"abstract":"<p><p>BBT-059, a long-acting PEGylated interleukin-11 (IL-11) analog that is believed to have hematopoietic promoting and anti-apoptotic properties, is being developed as a potential radiation medical countermeasure (MCM) for hematopoietic acute radiation syndrome (H-ARS). This agent has been shown to improve survival in lethally irradiated mice. To further evaluate the drug's toxicity and safety profile, 12 naïve nonhuman primates (NHPs, rhesus macaques) were administered one of three doses of BBT-059 subcutaneously and were monitored for the next 21 days. Blood samples were collected throughout the study to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of the drug as well as its effects on complete blood counts, cytokines, vital signs, and to conduct metabolomic studies. No adverse effects were detected in any treatment group during the study. Short-term changes in metabolomic profiles were present in all groups treated with BBT-059 beginning immediately after drug administration and reverting to near normal levels by the end of the study period. Several pathways and metabolites, particularly those related to inflammation and steroid hormone biosynthesis, were activated by BBT-059 administration. Taken together, these observations suggest that BBT-059 has a good safety profile for further development as a radiation MCM for regulatory approval for human use.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"26-37"},"PeriodicalIF":2.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11295257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140877159","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":"A Novel TGFβ Receptor Inhibitor, IPW-5371, Prevents Diet-induced Hepatic Steatosis and Insulin Resistance in Irradiated Mice.","authors":"Alexandria M Szalanczy, Chrissy Sherrill, Katherine M Fanning, Barry Hart, David Caudell, Ashley W Davis, Jordyn Whitfield, Kylie Kavanagh","doi":"10.1667/RADE-23-00202.1","DOIUrl":"10.1667/RADE-23-00202.1","url":null,"abstract":"<p><p>As the number of cancer survivors increases and the risk of accidental radiation exposure rises, there is a pressing need to characterize the delayed effects of radiation exposure and develop medical countermeasures. Radiation has been shown to damage adipose progenitor cells and increase liver fibrosis, such that it predisposes patients to developing metabolic-associated fatty liver disease (MAFLD) and insulin resistance. The risk of developing these conditions is compounded by the global rise of diets rich in carbohydrates and fats. Radiation persistently increases the signaling cascade of transforming growth factor β (TGFβ), leading to heightened fibrosis as characteristic of the delayed effects of radiation exposure. We investigate here a potential radiation medical countermeasure, IPW-5371, a small molecule inhibitor of TGFβRI kinase (ALK5). We found that mice exposed to sub-lethal whole-body irradiation and chronic Western diet consumption but treated with IPW-5371 had a similar body weight, food consumption, and fat mass compared to control mice exposed to radiation. The IPW-5371 treated mice maintained lower fibrosis and fat accumulation in the liver, were more responsive to insulin and had lower circulating triglycerides and better muscle endurance. Future studies are needed to verify the improvement by IPW-5371 on the structure and function of other metabolically active tissues such as adipose and skeletal muscle, but these data demonstrate that IPW-5371 protects liver and whole-body health in rodents exposed to radiation and a Western diet, and there may be promise in using IPW-5371 to prevent the development of MAFLD.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"1-10"},"PeriodicalIF":2.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076528","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":"Revisiting an Inverse Dose-Fractionation Effect of Ionizing Radiation Exposure for Ischemic Heart Disease: Insights from Recent Studies.","authors":"Lydia B Zablotska, Mark P Little, Nobuyuki Hamada","doi":"10.1667/RADE-00230.1","DOIUrl":"10.1667/RADE-00230.1","url":null,"abstract":"<p><p>Over the last two decades, there has been emerging evidence suggesting that ionizing radiation exposures could be associated with elevated risks of cardiovascular disease (CVD), particularly ischemic heart disease (IHD). Excess CVD risks have been observed in a number of exposed groups, with generally similar risk estimates both at low and high radiation doses and dose rates. In 2014, we reported for the first time significantly higher risks of IHD mortality when radiation doses were delivered over a protracted period of time (an inverse dose-fractionation effect) in the Canadian Fluoroscopy Cohort Study. Here we review the current evidence on the dose-fractionation effect of radiation exposure, discuss potential implication for radiation protection policies and suggest further directions for research in this area.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"80-86"},"PeriodicalIF":2.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11260496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076561","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}