International journal of radiation biology最新文献

{"title":"Cholesterol content and membrane properties in metastatic melanoma compared to primary melanoma: an EPR-based study.","authors":"Faustyna Pachacz, Alicja Gazda, Anna Wiśniewska-Becker, Agnieszka Wolnicka-Glubisz","doi":"10.1080/09553002.2026.2686692","DOIUrl":"https://doi.org/10.1080/09553002.2026.2686692","url":null,"abstract":"<p><strong>Purpose: </strong>Melanoma is a malignant tumor originating from melanocytes and characterized by a rapidly increasing incidence worldwide. Its high mortality rate is primarily due to its high metastatic potential. The aim of this study was to compare the physicochemical properties of liposomes prepared from lipids extracted from primary (WM115) and metastatic (WM266.4) melanoma cells in order to better understand the lipid-related changes associated with melanoma progression.</p><p><strong>Methods: </strong>Lipids were extracted from WM115 and WM266.4 melanoma cells using the Folch method, labeled with the 16-PC spin probe, and rehydrated to form multilamellar liposomes. Electron paramagnetic resonance (EPR) spectroscopy was performed to assess membrane fluidity and polarity, while cholesterol content and lipid droplet accumulation were also quantified.</p><p><strong>Results: </strong>Liposomes prepared from lipids extracted from both cancer cell lines (metastatic WM266.4 and primary WM115 cells) exhibited high order parameters and low polarity, resembling cholesterol-enriched model membranes. However, chemiluminescence analyses revealed higher cholesterol levels and greater lipid droplet accumulation in WM266.4 cells, indicating distinct lipid organization associated with melanoma progression.</p><p><strong>Conclusions: </strong>These findings indicate clear differences in cholesterol content between primary and metastatic melanoma cells, highlighting the potential role of lipid remodeling in melanoma progression.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1-11"},"PeriodicalIF":2.4,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148267551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Double electron-electron resonance (DEER) structural study of the holo and apo states of calmodulin.","authors":"S Ronan Fisher, Elena M Mocanu, Anokhi Shah, Janet E Lovett","doi":"10.1080/09553002.2026.2686688","DOIUrl":"https://doi.org/10.1080/09553002.2026.2686688","url":null,"abstract":"<p><strong>Purpose: </strong>Human calmodulin-1 (CaM) undergoes calcium-dependent conformational changes that are difficult to capture owing to substantial structural flexibility. This study aims to show that double electron-electron resonance (DEER) spectroscopy can measure ensembles of CaM conformations. The most probable distances are compared to structural models from experimental structures and deep-learning predictions.</p><p><strong>Materials and methods: </strong>Four double-cysteine variants of a recombinant CaM were engineered for site-directed spin labeling. Spin-labeled CaM was measured with DEER spectroscopy in both the presence (holo CaM) and absence (apo CaM) of Ca(II). Distance distributions were compared with predictions derived from Protein Data Bank structures and models generated from AlphaFold2 and IntFOLD7. DEERefiner was used to generate conformers from these models using the distance-distributions as restraints.</p><p><strong>Results: </strong>The distance distributions from DEER were consistent with conformational heterogeneity. Distance distributions differed between apo and holo conditions. The results with Ca(II) were consistent with an ensemble of conformations including the canonical crystallographic structure (1CLL). Apo state distance distributions were not reproduced well by the models. Upon refinement with the distance distributions the models aligned better with the most probable distances from the apo and holo results. Comparisons of the refined models indicated that Ca(II) binding causes subtle rearrangements between EF-hand domains.</p><p><strong>Conclusions: </strong>The DEER-derived distance distributions for the four doubly-labeled CaM variants demonstrate that apo and holo CaM populate broad but different conformational ensembles in frozen solution. Comparison of apo and holo distributions indicate that Ca(II) binding induces a subtle, yet significant, structural rearrangement. These results illustrate how DEER-guided modeling can provide deeper insight into flexible protein ensembles that are not captured by existing static structures.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1-11"},"PeriodicalIF":2.4,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148267611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Empowering stakeholders and the dangers of normative science and stealth advocacy.","authors":"Lawrence A Kapustka","doi":"10.1080/09553002.2026.2675642","DOIUrl":"https://doi.org/10.1080/09553002.2026.2675642","url":null,"abstract":"<p><p>The purpose of this mini-review commentary is to elevate the quality of dialogue among stakeholders who are focussed on meeting energy demands. Rising demand for energy has spurred interest in expanding technologies including refinements in nuclear energy facilities, particularly small modular reactors (SMRs). Promotion of SMRs has focused extensively on explaining the technological advances. This commentary explores the importance of stakeholder engagement and makes a plea to avoid the trappings of normative science and stealth advocacy. If genuine engagement of stakeholders can be achieved, the stage can be set to accommodate and address the critical concerns of all affected stakeholders.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1-3"},"PeriodicalIF":2.4,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A metal ion-dependent mechanism promoting gain of function in NEIL1 variants.","authors":"Jamie T Zuckerman, Irina G Minko, Terry P Lybrand, Martin Egli, Amanda K McCullough, R Stephen Lloyd","doi":"10.1080/09553002.2026.2654426","DOIUrl":"https://doi.org/10.1080/09553002.2026.2654426","url":null,"abstract":"<p><strong>Purpose: </strong>Maintenance of genomic integrity following ionizing radiation (IR) and chemical exposures is primarily a function of the base excision repair (BER) pathway. This genome surveillance is initiated by DNA glycosylases, with the endonuclease VIII-like 1 (NEIL1) glycosylase, apurinic/apyrimidinic site (AP) lyase being responsible for the release of IR-induced DNA lesions. Suppressed expression of <i>NEIL1</i> leads to increased IR cytotoxicity. Previous analyses of a single nucleotide polymorphic (SNP) variant of NEIL1, Thr103Ala (T103A), revealed compromised catalytic activities. This investigation was designed to determine the mechanisms underlying the deficiencies of T103A.</p><p><strong>Materials and methods: </strong>Mutant and variant NEIL1 enzymes were constructed and characterized for their ability to catalyze incision of DNAs containing site-specific base damages. Molecular dynamics (MD) simulations of wild-type (WT) and T103A variant NEIL1 using the NEIL1 crystal structure, addressed mechanisms conferring catalytic activity changes.</p><p><strong>Results: </strong>The glycosylase and AP lyase activities of NEIL1 T103A could be partially restored in the presence of Mg²⁺. The catalytic activities of T103S were also stimulated by this metal. Similar increases of the reaction rates of T103A and T103S were observed in the presence of Ca²⁺. In contrast, the activities of WT NEIL1 and T103V mutant were not stimulated by the addition of these metals. MD simulations reveal that the surface loop (residues 102-110) displays enhanced conformational fluctuations in the T103A variant compared to that region in WT NEIL1. Mg²⁺ hexahydrate coordinated to carbonyl oxygens of loop residues dampens loop dynamics.</p><p><strong>Conclusion: </strong>This study is the first report of the metal-dependent stimulation of compromised activities in a DNA glycosylase variant. The MD simulations suggest that Mg²⁺ stabilizes the surface loop dynamics in the T103A variant, with the effects of the T to A substitution and Mg²⁺ presence being transmitted over a distance greater than 26 Å to the NEIL1 active site.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1-10"},"PeriodicalIF":2.4,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"8-Oxoguanine DNA glycosylase1 repairactome: transcriptional reprogramming in radiation-induced lung injury.","authors":"Lang Pan, Shunzi Jin, Spiros Vlahopoulos, Zsolt Radak, Attila Bacsi, Istvan Boldogh, Xueqing Ba","doi":"10.1080/09553002.2026.2647952","DOIUrl":"10.1080/09553002.2026.2647952","url":null,"abstract":"<p><strong>Purpose: </strong>This narrative review aims to elucidate the interconnections between ionizing radiation (IR)-induced oxidative base modification(s) and gene expression reprogramming that promote tissue repair, driving lung fibrosis and ultimately resulting in life-threatening organ dysfunction with limited therapeutic options.</p><p><strong>Conclusions: </strong>IR introduces diverse chemical modifications into chromatin, affecting both histones and DNA, both directly or indirectly through reactive oxygen and nitrogen species. Among DNA bases, guanine -an electron-rich heterocycle-is the most susceptible to oxidation, primarily forming 8-oxo-7,8-dihydroguanine (8-oxoGua). Long regarded solely as a mutagenic biomarker of oxidative stress, 8-oxoGua is now recognized as an epigenetic-like mark that serves as a platform for anchoring 8-oxoguanine DNA glycosylase 1 (OGG1), that interacts with both chromatin remodelers and transcription factors, thus, promoting essential transcription initiation complex assembly. In this capacity, the OGG1 repairactome acts as a signaling hub rather than merely an initiator of base excision repair and is essential for transcriptional reprogramming toward controlled and/or unrestrained inflammatory and profibrotic programs. These include those mediated by TGF-β/SMAD signaling that drives myofibroblast differentiation and extracellular matrix deposition in promoting tissue repair. Notably, pharmacological inhibition of OGG1 repairactome formation markedly attenuates pulmonary pathologies induced by the radiomimetic agent bleomycin or by TGF-β1, thereby preserving and improving lung function in experimental models.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1-13"},"PeriodicalIF":2.4,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147617240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the mechanisms of the use of nitroxide as antioxidant for ultra high molecular weight polyethylene.","authors":"Marina Chumakov Rozenblat, Sara Goldstein, Julia Diane Schexnayder, Aiysha Ashfaq, Mohamad Al-Sheikhly","doi":"10.1080/09553002.2026.2643772","DOIUrl":"https://doi.org/10.1080/09553002.2026.2643772","url":null,"abstract":"<p><strong>Purpose: </strong>Ultra-high molecular weight polyethylene (UHMWPE) is commonly used as a lining material in total joint arthroplasty; however, irradiation used for sterilization and crosslinking generates free radicals that increase the material's susceptibility to oxidative aging. This study explores the efficacy of nitroxides in scavenging free radicals in UHMWPE and their impact on crosslink density.</p><p><strong>Material and methods: </strong>The irradiation and crosslinking of UHMWPE polymer specimens were performed using a ⁶⁰Co γ-ray source and a 7 MeV electron accelerator at the University of Maryland. The scavenging of alkyl radicals and the degree of crosslinking in UHMWPE were assessed using Electron Paramagnetic Resonance (EPR) spectroscopy and gel swelling in decalin solvent, as measured by a Thermomechanical Analyzer (TMA).</p><p><strong>Results: </strong>The nitroxide radicals TEMPO and TEMPOL demonstrated high efficiency in scavenging alkyl radicals. It was noted that without oxygen and antioxidants, most alkyl radicals undergo bimolecular reactions, resulting in crosslinks. When nitroxides are present, residual radicals combine with nitroxides or form long-lasting allyl radicals. The addition of nitroxide antioxidants, which efficiently scavenge free radicals, can prevent crosslinking if they diffuse into the polymer before irradiation, scavenging residual radicals within a crosslinked polymer. While it is possible to create highly crosslinked UHMWPE with nitroxides by adjusting factors such as dose, dose rate, irradiation temperature, and the duration of nitroxide doping, it was found that at low gamma dose rates, nitroxides nearly entirely inhibited crosslinking.</p><p><strong>Conclusions: </strong>When added before or after irradiation, nitroxides effectively scavenge residual free radicals while maintaining crosslink density. However, specific scenarios may inhibit crosslinking in the presence of nitroxide.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1-12"},"PeriodicalIF":2.4,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147617227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of protein and metabolomic blood biomarkers enhances classification of radiation exposure in X-irradiated humanized mice.","authors":"Sunain Deol, Meth Jayatilake, Maria Taveras, Qi Wang, Shivani Bansal, Yaoxiang Li, Xuefeng Wu, Marjan Boerma, Helen C Turner, Amrita K Cheema","doi":"10.1080/09553002.2026.2645909","DOIUrl":"10.1080/09553002.2026.2645909","url":null,"abstract":"<p><strong>Purpose: </strong>The general population is at risk of exposure to ionizing radiation due to nuclear warfare, terrorism, or radiological accidents. Such exposures can lead to acute radiation syndrome (ARS), a set of debilitating and often fatal health effects that start within the first week after irradiation. ARS is largely defined by injuries to the bone marrow and intestinal tract, two organ systems that are highly sensitive to the deleterious effects of ionizing radiation. There is currently no FDA-approved, minimally invasive assay to identify absorbed radiation dose in subjects suspected to have been exposed to ionizing radiation. Moreover, no methods are available for the early detection of radiation injuries, such that intervention strategies can be implemented before injuries become life-threatening. The primary objective of this study was to develop a multiparameter targeted biomarker approach to improve dose and injury assessment using X-irradiated humanized mice as a model.</p><p><strong>Materials and methods: </strong>Metabolomic and proteomic analyses were performed on plasma and leukocytes derived from blood collected 2 and 7 days after X-ray exposure (doses 0, 1, 2, and 3 Gy). The dose-dependent depletion of human blood cell lymphocytes (T and B cells) was used as a surrogate for bone marrow injury after radiation exposure. Multiple machine learning models were used for predictive modeling.</p><p><strong>Results: </strong>Multimodal integration of proteomic, lipidomic, and metabolomic analytes in blood cells (leukocytes) improved the performance metrics for binary classification (AUC > 0.95) on day 7 after exposure. Moreover, this integrated approach was able to distinguish between high-dose (2 and 3 Gy) and low-dose (1 Gy) exposure (AUC > 0.9), demonstrating its potential utility for biomarker-based assessment.</p><p><strong>Conclusions: </strong>The findings highlight the potential for a multiparameter biomarker approach in human leukocytes for radiation exposure. With further validation studies, this approach could be leveraged for novel dosimetry algorithms for human use.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1-14"},"PeriodicalIF":2.4,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147583337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromosomal damage in breast cancer patients undergoing different radiotherapy schemes.","authors":"Renu Dayal, Lama Ramadan, Liv Veldeman, Carlos Murillo, Mirthe Vandenputte, Thea De Pauw, Magdalena Płódowska, Halina Lisowska, Aneta Węgierek-Ciuk, Janusz Braziewicz, Prabodha Kumar Meher, Andrzej Wojcik, Anne Vral, Ans Baeyens","doi":"10.1080/09553002.2026.2636304","DOIUrl":"https://doi.org/10.1080/09553002.2026.2636304","url":null,"abstract":"<p><strong>Purpose: </strong>Radiotherapy (RT) remains a cornerstone in breast cancer (BC) treatment. While RT is effective, exposure to surrounding healthy tissues can lead to chromosomal damage and potentially increase the risk of secondary cancers. This study investigated chromosomal damage in circulating lymphocytes of BC patients receiving different RT schemes: ultra-hypofractionation in five fractions (UHF) and moderate hypofractionation in either 10-15 fractions (MHF-low) or 20 fractions (MHF-high). We also aimed to investigate how RT parameters influence MN yields in lymphocytes of BC patients. Additionally, the in vitro chromosomal radiosensitivity of primary and second primary BC patients was evaluated.</p><p><strong>Materials and methods: </strong>Blood samples were collected pre- and post-RT from 182 primary and 50 second primary BC patients. Chromosomal damage was assessed in lymphocytes using the cytokinesis-block micronucleus (CBMN) assay. To evaluate chromosomal radiosensitivity, all blood samples were irradiated in vitro with 1 Gy of X-ray before performing the CBMN assay. Associations of MN yields with cancer type, RT scheme, lymph node irradiation, boost dose delivery, and irradiated body volume were analyzed using linear regression and linear mixed-effects models.</p><p><strong>Results: </strong>Our findings indicated no difference in MN yields between primary and second primary BC patients. MHF-high RT scheme was associated with the highest MN induction, while the UHF scheme resulted in the lowest. Additionally, increased chromosomal damage was correlated with higher total tumor doses, larger irradiated volumes, and lymph node irradiation. No significant difference in in vitro chromosomal radiosensitivity was observed between primary and second primary BC patients.</p><p><strong>Conclusions: </strong>Shorter RT scheme with higher dose per fraction may mitigate cytogenetic damage in circulating lymphocytes, offering potential advantages in long-term safety profiles. In vitro chromosomal radiosensitivity, as assessed by CBMN assay is not a hallmark for second primary BC risk.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1-12"},"PeriodicalIF":2.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147380067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Demographic and clinical profiles of patients with primary and second primary cancers: identifying biomarkers of sensitivity to radiotherapy-induced cancer.","authors":"Magdalena Płódowska, Lama Ramadan, Renu Dayal, Kinga Pasińska, Prabodha Kumar Meher, Aneta Węgierek-Ciuk, Halina Lisowska, Anna Lankoff, Janusz Braziewicz, Jacek Sadowski, Piotr Kędzierawski, Marzia Palma, Liv Veldeman, Tom Boterberg, Anne Vral, Ans Baeyens, Andrzej Wojcik","doi":"10.1080/09553002.2026.2629245","DOIUrl":"https://doi.org/10.1080/09553002.2026.2629245","url":null,"abstract":"<p><strong>Purpose: </strong>Due to improved therapy, the life expectancy of cancer patients is increasing, and with this, the incidence of radiotherapy (RT)-induced second primary cancers (SPCs). We investigated whether genetic factors may contribute to SPC susceptibility.</p><p><strong>Materials and methods: </strong>We collected peripheral blood samples from 232 patients treated by external beam RT for a first primary cancer (FPC) of breast, brain and the lymphatic tissue and from 96 unrelated patients who developed various SPC. Samples from patients with FPC were collected before start of RT and at one or two timepoints after the last RT fraction. Samples from patients with SPC were collected at admission to the hospital and, if the patient was treated by RT, once after the last fraction. Peripheral blood mononuclear cells (PBMCs) were isolated, cryopreserved and shipped to project partners. They were analyzed for RT-induced chromosomal aberrations, micronuclei (MN) and γH2AX foci. In addition, the response of PBMC to an in vitro dose was analyzed at the level of MN and γH2AX foci. Whole genomic DNA of samples collected at admission to the hospital was isolated and sequenced to identify possible single nucleotide polymorphisms that characterize patients with SPC.</p><p><strong>Results: </strong>The logistics of blood collection, cryopreservation, sample shipments and the demographic and clinical data of the patients are provided. The breast FPC and SPC patients came from Ghent, Belgium and Kielce, Poland. Brain FPC patients came from Kielce and Hodgkin lymphoma FPC patients from Stockholm, Sweden. Differences were seen between patients that came from Ghent and Kielce regarding age at diagnosis, RT dose, chemotherapy treatment and time between FPC and SPC. These differences do not pose problems for reaching the aims of the study.</p><p><strong>Conclusions: </strong>The data presented here serve as the basis for interpreting the results of the experimental assays that are presented in separate papers.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1-12"},"PeriodicalIF":2.4,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147277861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary: the oxygen effect as a possible contributing factor to the mechanism for FLASH protection of normal tissue.","authors":"Cameron J Koch","doi":"10.1080/09553002.2026.2630997","DOIUrl":"https://doi.org/10.1080/09553002.2026.2630997","url":null,"abstract":"<p><strong>Purpose: </strong>Despite seven decades of research on radiation protection by thiols and radiation sensitization by oxygen, there is no universal agreement on their interaction in defining the overall radiation response of (mammalian) cells. Thus, even in modern textbooks, the 'Oxygen Effect' (greater radiation resistance at reduced oxygen levels) is typically described using the same equation derived by Howard-Flanders and Alper in 1957 for bacterial cells and yeasts, without consideration for the impact of thiols (unknown at that time). A major contributing factor to this lack of agreement involves the very low oxygen concentrations (µM range) required for radiation sensitization. This causes severe challenges to oxygen measurement and control, and is further complicated by the depletion of oxygen by radiation itself (radiation chemical oxygen depletion - ROD). Recently, an unexpected protection of normal (but not tumor) tissue was found for radiation delivered at >40 Gy/s (FLASH), compared with conventional (<1 Gy/s) dose rates. A possible mechanism for FLASH was suggested to involve ROD, leading to reduced tissue oxygenation and protection through the oxygen effect.</p><p><strong>Conclusions: </strong>This commentary will review the discovery of the 'Oxygen Effect', discuss problems associated with original and alternative models, and summarize a radiation-chemistry-based model that is relevant to interest in dose-modification. The radiation chemistry background to this model shows directly how radiation depletes oxygen (and other molecules) and that while this depletion is a part of the oxygen effect, it does not define it. Finally, the impact of a shift in half-maximal resistance on radiation protection by FLASH will be illustrated.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1-9"},"PeriodicalIF":2.4,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147277844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}