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PNA-FISH-based Chromosome Aberration Frequency and Serum IL-6 as Predictive Biomarkers for Radiation Therapy-induced Pneumonitis in Lung Cancer Patients. 基于pna - fish的染色体畸变频率和血清IL-6作为肺癌患者放射治疗性肺炎的预测性生物标志物
IF 2.5 3区 医学
Radiation research Pub Date : 2025-06-06 DOI: 10.1667/RADE-25-00013.1
Gloriamaris Loy-Caraos, Nobuki Imano, Ikuno Nishibuchi, Yuji Murakami, Nafiseh Mirkatouli, Seiko Hirota, Shinji Yoshinaga, Yoshitaka Kamimura, Yuri Kawashima, Jiying Sun, Satoshi Tashiro
{"title":"PNA-FISH-based Chromosome Aberration Frequency and Serum IL-6 as Predictive Biomarkers for Radiation Therapy-induced Pneumonitis in Lung Cancer Patients.","authors":"Gloriamaris Loy-Caraos, Nobuki Imano, Ikuno Nishibuchi, Yuji Murakami, Nafiseh Mirkatouli, Seiko Hirota, Shinji Yoshinaga, Yoshitaka Kamimura, Yuri Kawashima, Jiying Sun, Satoshi Tashiro","doi":"10.1667/RADE-25-00013.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00013.1","url":null,"abstract":"<p><p>Accurate prediction of symptomatic radiation therapy-induced pneumonitis (RT-IP) remains an important clinical challenge. Currently, mean lung dose and volume of the lungs receiving a 20 Gy threshold of ≤20 Gy and ≤35%, respectively, are utilized to reduce the incidence of pneumonitis to 20%. However, its occurrence is not entirely predictable even at the recommended threshold levels. Hence, in this study, we aimed to evaluate several biological markers, specifically chromosome aberrations by peptide nucleic acid fluorescence in situ hybridization (PNA-FISH), γH2AX, serum IL-6, and IL-17, as potential predictors of symptomatic (grade ≥2) radiation therapy-induced pneumonitis. We prospectively enrolled patients with locally advanced lung cancer. Peripheral blood samples were collected from eleven patients before, during (2 Gy, 20 Gy, 60/66 Gy), and one month after chemoradiotherapy. We then compared these biomarkers between overreactors (grade ≥2 RT-IP) and non-overreactors (grade 0 to 1 RT-IP). Our findings show that chromosome aberration frequency, serum IL-6, and IL-17 after 20 Gy are higher in overreactors than in non-overreactors. Moreover, overreactors accumulated more complex aberrations, such as tricentrics, quadricentrics, and quintacentrics. While chromosome aberration frequency correlated with mean lung dose and IL-17, a pneumonitis marker, IL-6 correlated with the irradiated volume after 20 Gy. Receiver operating characteristic curve analysis further showed that chromosome aberration frequency and IL-6 have the highest specificity for predicting grade ≥2 RT-IP among the assays. In conclusion, we demonstrated the superior predictive capability of PNA-FISH-based chromosome aberration frequency and serum IL-6 for radiation therapy-induced pneumonitis in lung cancer patients. This supports the usefulness of these biomarkers for predicting radiation therapy-induced pneumonitis.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234964","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
Understudied Populations in Radiation Exposure Research: Needs, Challenges, and Mitigation Strategies. 辐射暴露研究中未充分研究的人群:需求、挑战和缓解策略。
IF 2.5 3区 医学
Radiation research Pub Date : 2025-06-04 DOI: 10.1667/RADE-24-00263.1
Lanyn P Taliaferro, Jeffrey C Buchsbaum, Andrea L DiCarlo, Cinnamon A Dixon, Francesca Macchiarini, Merriline M Satyamitra, Mercy PrabhuDas, Michael W Rudokas
{"title":"Understudied Populations in Radiation Exposure Research: Needs, Challenges, and Mitigation Strategies.","authors":"Lanyn P Taliaferro, Jeffrey C Buchsbaum, Andrea L DiCarlo, Cinnamon A Dixon, Francesca Macchiarini, Merriline M Satyamitra, Mercy PrabhuDas, Michael W Rudokas","doi":"10.1667/RADE-24-00263.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00263.1","url":null,"abstract":"<p><p>This workshop examined the effects of ionizing radiation on certain understudied populations, including pregnant/lactating, in utero, pediatric, and geriatric populations. Research using animal models has revealed significant age and condition-related differences in radiation-induced injuries, highlighting the need for tailored triage and treatment strategies. Historical data from Hiroshima, Nagasaki, and Chernobyl further support these findings, demonstrating that radiation effects lead to wide-ranging issues with unique profiles during pregnancy, childhood and elderly age. While some research has been conducted on these groups, ethical and logistical challenges make it difficult to study these populations extensively. Therefore, developing alternative approaches that offer promising avenues for further research is critical. Radiation-induced biomarkers and biodosimetry also show age-related differences, including distinctive metabolic disruptions, necessitating further validation of biodosimetry tools. These findings emphasize the importance of considering age, sex, and demographic factors in preclinical and clinical radiation research to develop treatments that improve outcomes of understudied populations after a radiological or nuclear public health emergency.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216722","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
Quantifying Sensitivity of Carbon RBE Models to Reference Parameter Variations. 量化碳RBE模型对参考参数变化的敏感性。
IF 2.5 3区 医学
Radiation research Pub Date : 2025-06-02 DOI: 10.1667/RADE-24-00162.1
Shannon Hartzell, Fada Guan, Giuseppe Magro, Paige Taylor, Christine B Peterson, Stephen F Kry
{"title":"Quantifying Sensitivity of Carbon RBE Models to Reference Parameter Variations.","authors":"Shannon Hartzell, Fada Guan, Giuseppe Magro, Paige Taylor, Christine B Peterson, Stephen F Kry","doi":"10.1667/RADE-24-00162.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00162.1","url":null,"abstract":"<p><p>Models used to calculate the relative biological effectiveness (RBE) of carbon-ion radiotherapy include the microdosimetric kinetic model (MKM), stochastic MKM (SMKM), repair-misrepair-fixation (RMF) model, and local effect model I (LEM). We compared the sensitivities of these models to variations in input biological and reference parameters. We used Monte Carlo simulations of clinically realistic carbon-ion beams incident on a phantom and scored input parameters for RBE models (kinetic energy, microdosimetric spectra, double-strand break yield, and physical dose). We combined data with cell- and model-specific parameters to calculate the linear (α) and quadratic (β) components of the carbon-ion beam, which were used along with the reference α and β values and dose to calculate RBE. Model sensitivity to parameters was quantified by statistically introducing uncertainty into independent parameters and sampling the resultant RBE. To assess histological differences contributing to variations in the RBE, we also used various reference cell lines. We recalculated the RBE using different reported datasets within individual cell lines to compare inter- and intra-cell line variability. The variability introduced by inherent measurement and estimation uncertainty was typically 26% for the microdosimetric models, 25% for the RMF model, and 30% for the LEM at the 1-σ level. The variability across cell lines, which averaged 27% for the microdosimetric models and 2.5% for the RMF model, was similar to the intra-cell line variability in the RBE as calculated with unique datasets for an individual cell line. While the focus is largely on comparing models, the results of this study indicate that the variation in RBE within each model, based solely on reference parameters, is substantial. Our findings indicate that the selection of input parameters is of comparable importance to the choice of cell line and even the RBE model. This study provides insight into model robustness and emphasizes the need for continued computational and in-vitro RBE research.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199918","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
Maternal High-fat Diet Modulates Radiosensitivity of Hematopoietic Tissue in Male Offspring. 母体高脂肪饮食调节雄性后代造血组织的放射敏感性。
IF 2.5 3区 医学
Radiation research Pub Date : 2025-06-01 DOI: 10.1667/RADE-24-00163.1
Takanori Katsube, Masahiro Murakami, Kaoru Tanaka, Takamitsu Morioka, Shizuko Kakinuma, Bing Wang
{"title":"Maternal High-fat Diet Modulates Radiosensitivity of Hematopoietic Tissue in Male Offspring.","authors":"Takanori Katsube, Masahiro Murakami, Kaoru Tanaka, Takamitsu Morioka, Shizuko Kakinuma, Bing Wang","doi":"10.1667/RADE-24-00163.1","DOIUrl":"10.1667/RADE-24-00163.1","url":null,"abstract":"<p><p>Obesity is a growing global health concern, and the Western diet characterized by its high-calorie and high-fat content, is widely acknowledged as a major contributor. Obesity is closely linked to the onset of various metabolic syndromes in affected individuals. Furthermore, maternal obesity has been revealed to have persistent effects on the long-term health of offspring, a phenomenon widely recognized as the \"developmental origins of health and disease\" (DOHaD). In this study, we aimed to explore the potential modifying effects of maternal exposure to a high-fat diet (HFD) on the health outcomes of offspring after exposure to ionizing radiation. C57BL/6J female mice were fed either an HFD or a standard diet (STD) immediately after weaning at 3 weeks of age. At 10 weeks of age, they were mated with C3H/He male mice raised on an STD. The resulting pups were nursed by their dams and were subjected to a total body X-ray dose of 3.8 Gy at 7 days after birth. All pups were weaned onto an STD at 4 weeks of age, irrespective of their experimental group. Lifelong observation of these pups demonstrated that maternal exposure to HFD reduced the lifespan of male offspring postirradiation, whereas maternal HFD alone did not significantly impact the lifespan of both male and female offspring. Pathological analysis revealed that the lifespan shortening by maternal HFD after X irradiation was primarily attributed to early deaths associated with depletion of bone marrow cells and thymic lymphoma within 6 months after X irradiation. To the best of our knowledge, this is the first report showcasing the modifying effects of maternal HFD on the radiosensitivity of offspring.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"398-409"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050840","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 Radioprotective Effects of 16, 16 dimethyl Prostaglandin E2 on Survival and Hematopoiesis are Mediated Through Co-Stimulation of the EP3 and EP4 Receptors. 16,16二甲基前列腺素E2通过共同刺激EP3和EP4受体介导的放射保护作用对生存和造血的影响。
IF 2.5 3区 医学
Radiation research Pub Date : 2025-06-01 DOI: 10.1667/RADE-24-00176.1.S1
Seiji Fukuda, Andrea M Patterson, Tong Wu, Pratibha Singh, P Artur Plett, Hailin Feng, Carol H Sampson, Christie M Orschell, Louis M Pelus
{"title":"The Radioprotective Effects of 16, 16 dimethyl Prostaglandin E2 on Survival and Hematopoiesis are Mediated Through Co-Stimulation of the EP3 and EP4 Receptors.","authors":"Seiji Fukuda, Andrea M Patterson, Tong Wu, Pratibha Singh, P Artur Plett, Hailin Feng, Carol H Sampson, Christie M Orschell, Louis M Pelus","doi":"10.1667/RADE-24-00176.1.S1","DOIUrl":"10.1667/RADE-24-00176.1.S1","url":null,"abstract":"&lt;p&gt;&lt;p&gt;16, 16 dimethyl-Prostaglandin E2 (dmPGE2) administered prior to lethal irradiation protects against mortality from the hematopoietic acute radiation syndrome (H-ARS). It protects hematopoietic stem (HSC) and progenitor (HPC) cells and accelerates hematopoietic recovery by attenuating mitochondrial compromise, epigenetic downregulation of p53, and inhibition of histone acetylation at the promoters of genes involved in cell cycle, DNA repair and apoptosis. Since PGE2 mediates it effects through 4 conserved G-protein coupled receptors (EP1-4) we utilized highly selective EP receptor agonists to identify the EP receptors mediating radioprotection in H-ARS and evaluated the genes, cellular pathways and biological functions downstream of the EP receptors involved in HSC radioprotection. Radioprotection of mice from lethal radiation exposure was observed for the EP3 agonist sulprostone (65% survival) and the EP4 agonist rivenprost (50% survival), with the combination of EP3 + EP4 agonists providing 100% survival. Misoprostol, a PGE1 analog with similar EP receptor affinities as dmPGE2 also provided &gt;90% survival. The combination of EP3 and EP4 agonists was highly efficacious in accelerating recovery of all peripheral blood cell counts. Analysis of bone marrow HSPC populations from lethally irradiated mice by flow cytometry indicated that the EP3 + EP4 agonist combination trended closest to dmPGE2 in protecting total HSC and HPC, preventing early entry of these cells into cell cycle, and attenuating radiation-induced upregulation of the proapoptotic death receptor Fas, with similar activity also shown by misoprostol. Several genes involved in cell cycle and/or apoptosis control were upregulated (s1pr1, arrdc3, osm) or downregulated (hcar2 and cxcl10) in HSCs by all efficacious agonist treatments. Analysis of gene expression profiles and functional pathway analysis in HSC suggests that the EP4 receptor signals primarily through cAMP/PKA/CREB1, while EP3 signals primarily through a PI3K/Akt pathway initiated through activation of the Ras/Rho GTPases. In the combination setting, EP4 signaling appears dominant. Co-stimulation of EP3 and EP4 gave a stronger z-score for CREB1 activation with EP3 signaling augmenting/enhancing gene expression downstream of EP4 predominantly through CREB1. Comparison of KEGG pathways regulated by dmPGE2 and those regulated by the combination of EP3 + EP4 agonists indicate that both groups' TNF signaling pathways may be key functional components for radioprotection by dmPGE2 in HSC. Differentially expressed genes (DEG) associated with GTPase activity were observed in HSCs from mice treated with both EP3 and EP4 agonists likely contributing to their enhanced radioprotective effect mediated through the PI3K/Akt pathways downstream of both receptors. Some upstream regulators most strongly activated by dmPGE2 in bone marrow stromal cells overlapped with those observed in HSCs, with the most striking similarity being inhibition ","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"369-388"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043519","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
A Murine Model of Radionuclide Lung Contamination for the Evaluation of Americium Decorporation Treatments. 放射性核素肺污染小鼠模型用于评价镅去除治疗的效果。
IF 2.5 3区 医学
Radiation research Pub Date : 2025-06-01 DOI: 10.1667/RADE-25-00001.1
Trevor Arino, Alexia G Cosby, Jennifer Alvarenga-Vasquez, Kirsten E Martin, Alex Rigby, Adrianna Reece-Newman, Shereen Aissi, Ethan Hallick, Isaac Jaro, Rebecca J Abergel
{"title":"A Murine Model of Radionuclide Lung Contamination for the Evaluation of Americium Decorporation Treatments.","authors":"Trevor Arino, Alexia G Cosby, Jennifer Alvarenga-Vasquez, Kirsten E Martin, Alex Rigby, Adrianna Reece-Newman, Shereen Aissi, Ethan Hallick, Isaac Jaro, Rebecca J Abergel","doi":"10.1667/RADE-25-00001.1","DOIUrl":"10.1667/RADE-25-00001.1","url":null,"abstract":"<p><p>The hydroxypyridinone ligand 3,4,3-LI(1,2-HOPO) (HOPO), has been previously characterized as a promising chelating agent for in vivo decorporation of actinides, with decorporation being the removal of internally deposited contaminants from the body after exposure. The large majority of relevant literature reports have detailed the efficacy profile of HOPO as a decorporation agent in rodent models, where controlled radionuclide contamination is conducted via intravenous injection. However, this method of contamination does not necessarily reflect an accurate predictive model of the most probable biodistribution of free metal in the body. In the event of a radiological dispersal device or nuclear power plant accident scenario, it is most likely that first responders, military personnel, and victims of the event will be contaminated via air and water transmission. Therefore, research into the efficacy of chelating agents to treat lung-contaminated in vivo models needs to be carried out. Here, we establish a murine model with controlled, reproducible lung contamination using two different radionuclides, 89Zr and 241Am, for orthogonal biodistribution validation by positron emission tomography and ex vivo radioanalysis, respectively. In addition, we report effective chelation treatment of 241Am-contaminated lungs using HOPO, which improves decorporation by up to 40% compared to Ca-DTPA, the current standard of care.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"389-397"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812139","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
Octamer-Binding Transcription Factor 4 Inhibits HSC Functions via the NF-κB Signaling Pathway After 60Co Irradiation. 60Co辐照后八聚体结合转录因子4通过NF-κB信号通路抑制HSC功能
IF 2.5 3区 医学
Radiation research Pub Date : 2025-06-01 DOI: 10.1667/RADE-24-00258.1
Wenjing Yang, Xiaoe Jin, Chao Chen, Qianqian Zhang, Junyang Wang, Jinjia Liu, Lina Song, Xiaolong Jiang, Yunjian Liu, Weihong Li, Shufang Cui
{"title":"Octamer-Binding Transcription Factor 4 Inhibits HSC Functions via the NF-κB Signaling Pathway After 60Co Irradiation.","authors":"Wenjing Yang, Xiaoe Jin, Chao Chen, Qianqian Zhang, Junyang Wang, Jinjia Liu, Lina Song, Xiaolong Jiang, Yunjian Liu, Weihong Li, Shufang Cui","doi":"10.1667/RADE-24-00258.1","DOIUrl":"10.1667/RADE-24-00258.1","url":null,"abstract":"<p><p>High doses of radiation can cause irreversible bone marrow hematopoietic damage and even death. No effective strategies have been developed to protect against radiation effects in hematopoietic stem cells (HSCs). A total-body irradiation model was used to determine damage to HSCs. HSCs were sorted for transcriptome sequencing, and gene function analysis showed that Octamer-Binding Transcription Factor 4 (Oct4) increased significantly after irradiation. Oct4 deletion or inhibition of nuclear factor kappa-B (NF-κB) significantly reversed HSC apoptosis, promoted HSC colony formation, reduced cellular DNA damage, and promoted bone marrow regeneration after irradiation. ChIP assays showed that Oct4 binds to the IκB kinase (IKK) promoter region and increases the level of IKK. Overexpression of Oct4 significantly increased the entry of NF-κB into the nucleus after irradiation. NF-κB activators reversed the protective roles of knocking out Oct4. In vivo, the knockout of Oct4 and inhibition of NF-κB significantly improved the survival rate of mice after irradiation. We further found that the expression level of Oct4 decreased significantly in human leukemia cells, while the overexpression of Oct4 significantly increased the level of apoptosis in leukemia cells after irradiation. This study demonstrated a novel role of Oct4 in mediating apoptosis of HSCs after irradiation through the NF-κB pathway, providing an important biomedical strategy for the functional protection of HSCs in bone marrow after irradiation.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"433-444"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009508","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
ERRATUM. 勘误表。
IF 2.5 3区 医学
Radiation research Pub Date : 2025-06-01 DOI: 10.1667/RADE-25-e0001.1
{"title":"ERRATUM.","authors":"","doi":"10.1667/RADE-25-e0001.1","DOIUrl":"10.1667/RADE-25-e0001.1","url":null,"abstract":"","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":"203 6","pages":"447"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249302","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
Correlation Between DNA Double-Strand Break Distribution in 3D Genome and Ionizing Radiation-Induced Cell Death. 三维基因组DNA双链断裂分布与电离辐射诱导细胞死亡的相关性
IF 2.5 3区 医学
Radiation research Pub Date : 2025-06-01 DOI: 10.1667/RADE-24-00277.1
Ankang Hu, Wanyi Zhou, Xiyu Luo, Rui Qiu, Junli Li
{"title":"Correlation Between DNA Double-Strand Break Distribution in 3D Genome and Ionizing Radiation-Induced Cell Death.","authors":"Ankang Hu, Wanyi Zhou, Xiyu Luo, Rui Qiu, Junli Li","doi":"10.1667/RADE-24-00277.1","DOIUrl":"10.1667/RADE-24-00277.1","url":null,"abstract":"<p><p>The target theory is the most classical hypothesis explaining radiation-induced cell death, yet the physical or biological nature of the \"target\" remains ambiguous. This study hypothesizes that the distribution of DNA double-strand breaks (DSBs) within the 3D genome is a pivotal factor affecting the probability of radiation-induced cell death. We propose that clustered DSBs in DNA segments with high-interaction frequencies are more susceptible to leading to cell death than isolated DSBs. Topologically associating domains (TAD) can be regarded as the reference unit for evaluating the impact of DSB clustering in the 3D genome. To quantify this correlation between the DSB distribution in 3D genome and radiation-induced effect, we developed a simplified model considering the DSB distribution across TADs. Utilizing track-structure Monte Carlo codes to simulate the electron and carbon ion irradiation, and we calculated the incidence of each DSB case across a variety of radiation doses and linear energy transfers (LETs). Our simulation results indicate that DSBs in TADs with frequent interactions (case 3) are significantly more likely to induce cell death than clustered DSBs within a single TAD (case 2). Moreover, case 2 is significantly more likely to induce cell death than isolated DSBs (case 1). The curves of the incidence of cases 2 and 3 compared with LETs have a similar shape to the radiation quality factor (Q) used in radiation protection. This indicates that these two cases are also associated with the stochastic effects induced by high-LET radiation. Our study underscores the crucial significance of the 3D genome structure in the fundamental mechanisms of radiobiological effects. The hypothesis in our research offers novel perspectives on the mechanisms that regulate radiobiological effects. Moreover, it serves as a valuable reference for the establishment of mechanistic models that can predict cell survival under different doses and LETs.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"421-432"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812092","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
Antioxidants Ameliorates Ionizing Radiation-Induced Microcephaly in Cerebral Organoid Derived from Human-induced Pluripotent Stem Cells. 抗氧化剂改善电离辐射诱导的人类多能干细胞衍生的脑类器官小头畸形。
IF 2.5 3区 医学
Radiation research Pub Date : 2025-06-01 DOI: 10.1667/RADE-25-00017.1
Mikio Shimada, Yoshihisa Matsumoto
{"title":"Antioxidants Ameliorates Ionizing Radiation-Induced Microcephaly in Cerebral Organoid Derived from Human-induced Pluripotent Stem Cells.","authors":"Mikio Shimada, Yoshihisa Matsumoto","doi":"10.1667/RADE-25-00017.1","DOIUrl":"10.1667/RADE-25-00017.1","url":null,"abstract":"<p><p>Ionizing radiation exposure induces DNA damage and chromosome aberrations through both direct and indirect effect. The indirect effects are primarily mediated by the generation of hydroxyl radicals, a process attributed to radiation. Dimethyl sulfoxide (DMSO) and ascorbic acid (AA) are known as radical scavengers and have radioprotective effects. Radiation therapy is widely employed in the treatment of malignant tumors such as glioblastoma; however, its side effects, including cognitive impairments resulting from damage to healthy neurons, pose significant challenges. To ameliorate these effects, radioprotective reagents have been sought. In this study, we used cerebral organoids derived from human-induced pluripotent stem cells to address the radioprotective effect of radical scavengers, DMSO and AA in brain exposure. Although exposure to radiation for 20-day-old cerebral organoids results in DNA double-strand breaks and apoptosis leading to microcephaly phenotype, treatment with DMSO or AA not only before but also after radiation alleviated DNA damage, cell death, and the microcephaly phenotype. Our results suggest that DMSO and AA are candidates for the radioprotective reagents for brain tumor therapy.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"410-420"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027596","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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