{"title":"Effects of ionizing radiation exposure in offspring and next generations.","authors":"Christian Streffer, M Prakash Hande","doi":"10.1080/09553002.2024.2384834","DOIUrl":"10.1080/09553002.2024.2384834","url":null,"abstract":"","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1237-1239"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972484","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}
Victoria L Korogodina, Valeri B Arakelyan, Ashot A Chilingarian, Ruben Danielyan, Marina V Gustova, Svetlana P Kaplina, Garnik E Khachatryan, Arsen F Manucharyan, Gayane G Melik-Andreasyan, Balabek Sargsyan
{"title":"Adaptation to mountain γ-background: bacteria speciation.","authors":"Victoria L Korogodina, Valeri B Arakelyan, Ashot A Chilingarian, Ruben Danielyan, Marina V Gustova, Svetlana P Kaplina, Garnik E Khachatryan, Arsen F Manucharyan, Gayane G Melik-Andreasyan, Balabek Sargsyan","doi":"10.1080/09553002.2024.2396378","DOIUrl":"10.1080/09553002.2024.2396378","url":null,"abstract":"<p><strong>Purpose: </strong>To study the adaptation of bacteria to the natural γ-background of mountains and anthropogenic emissions from nuclear power plants; to establish the main factors of variability and speciation of bacteria.</p><p><strong>Method: </strong>Analysis of materials on the radiation background and its impact on living organisms in the landscape of Armenia, calculation of the absorbed dose by microbes due to rock radiation.</p><p><strong>Results: </strong>The review shows the death, reproduction, radioresistance and speciation of bacteria in changing conditions of low variable natural and anthropogenic γ-background.</p><p><strong>Conclusion: </strong>We assume that γ-rays from rocks activate cellular epigenetic mechanisms that regulate genome expression, signaling and, ultimately, variability of bacteria. Some of them have already been studied, others require research.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1517-1526"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335219","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}
Ingunn Hanson, Inga Solgård Juvkam, Olga Zlygosteva, Tine Merete Søland, Hilde Kanli Galtung, Eirik Malinen, Nina Frederike Jeppesen Edin
{"title":"TGF-β3 increases the severity of radiation-induced oral mucositis and salivary gland fibrosis in a mouse model.","authors":"Ingunn Hanson, Inga Solgård Juvkam, Olga Zlygosteva, Tine Merete Søland, Hilde Kanli Galtung, Eirik Malinen, Nina Frederike Jeppesen Edin","doi":"10.1080/09553002.2024.2324476","DOIUrl":"10.1080/09553002.2024.2324476","url":null,"abstract":"<p><strong>Purpose: </strong>Toxicities from head and neck (H&N) radiotherapy (RT) may affect patient quality of life and can be dose-limiting. Proteins from the transforming growth factor beta (TGF-β) family are key players in the fibrotic response. While TGF-β1 is known to be pro-fibrotic, TGF-β3 has mainly been considered anti-fibrotic. Moreover, TGF-β3 has been shown to act protective against acute toxicities after radio- and chemotherapy. In the present study, we investigated the effect of TGF-β3 treatment during fractionated H&N RT in a mouse model.</p><p><strong>Materials and methods: </strong>30 C57BL/6J mice were assigned to three treatment groups. The RT + TGF-β3 group received local fractionated H&N RT with 66 Gy over five days, combined with TGF-β3-injections at 24-hour intervals. Animals in the RT reference group received identical RT without TGF-β3 treatment. The non-irradiated control group was sham-irradiated according to the same RT schedule. In the follow-up period, body weight and symptoms of oral mucositis and lip dermatitis were monitored. Saliva was sampled at five time points. The experiment was terminated 105 d after the first RT fraction. Submandibular and sublingual glands were preserved, sectioned, and stained with Masson's trichrome to visualize collagen.</p><p><strong>Results: </strong>A subset of mice in the RT + TGF-β3 group displayed increased severity of oral mucositis and increased weight loss, resulting in a significant increase in mortality. Collagen content was significantly increased in the submandibular and sublingual glands for the surviving RT + TGF-β3 mice, compared with non-irradiated controls. In the RT reference group, collagen content was significantly increased in the submandibular gland only. Both RT groups displayed lower saliva production after treatment compared to controls. TGF-β3 treatment did not impact saliva production.</p><p><strong>Conclusions: </strong>When repeatedly administered during fractionated RT at the current dose, TGF-β3 treatment increased acute H&N radiation toxicities and increased mortality. Furthermore, TGF-β3 treatment may increase the severity of radiation-induced salivary gland fibrosis.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"767-776"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041206","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}
Na Li, Kejun Li, Wenyue Zhao, Yan Wang, Chang Xu, Qin Wang, Lifeng Pan, Qiang Li, Kaihua Ji, Ningning He, Yang Liu, Jinhan Wang, Manman Zhang, Mengmeng Yang, Liqing Du, Qiang Liu
{"title":"Small extracellular vesicles from irradiated lung epithelial cells promote the activation of fibroblasts in pulmonary fibrosis.","authors":"Na Li, Kejun Li, Wenyue Zhao, Yan Wang, Chang Xu, Qin Wang, Lifeng Pan, Qiang Li, Kaihua Ji, Ningning He, Yang Liu, Jinhan Wang, Manman Zhang, Mengmeng Yang, Liqing Du, Qiang Liu","doi":"10.1080/09553002.2023.2263550","DOIUrl":"10.1080/09553002.2023.2263550","url":null,"abstract":"<p><strong>Background: </strong>Alveolar epithelial injury and dysfunction are the risk factors for radiation-induced pulmonary fibrosis (RIPF). However, it is not clear about the relationship between RIPF and the small extracellular vesicles (sEV) secreted by irradiated alveolar epithelial cells. Based on the activation of fibroblasts, this study explored the role of sEV derived from alveolar epithelial cells in RIPF and the potential mechanisms.</p><p><strong>Methods: </strong>Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting were used to characterize sEV. Western blotting was used to detect fibrosis-associated proteins. Cell counts and transwell assays were used to evaluate the proliferation and migration ability of fibroblasts. RT-PCR was used to observe the extracellular matrix (ECM) synthesized by fibroblasts, miRNA changes in the sEV were determined by second-generation sequencing.</p><p><strong>Results: </strong>TEM, NTA, and western blotting showed the extracellular vesicles with a double-layer membrane structure of approximately 100 nm in diameter. The sEV derived from irradiated A549, HBEC3-KT, and MLE12 cells upregulated FN1 and alpha-SMA proteins expression in fibroblasts and drove the fibroblast to myofibroblast transition, and the sEV from irradiated mouse bronchoalveolar lavage fluid (BALF) affirmed the same results. In addition, the sEV derived from irradiated alveolar epithelial cells significantly increased the migration ability of fibroblasts and the expression of extracellular matrix proteins such as FN1. The results of miRNA sequencing of sEV in BALF of rats with RIPF showed that the metabolic pathway may be important for miRNA to regulate the activation of fibroblasts.</p><p><strong>Conclusion: </strong>The sEV derived from radiated pulmonary epithelial cells promote the activation, migration and extracellular matrix proteins expression of lung fibroblasts; miRNA in sEV may be an important molecular that affects the activation of lung fibroblasts.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"268-280"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41158489","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 clinician's perspective on boron neutron capture therapy: promising advances, ongoing trials, and future outlook.","authors":"Shumin Shen, Shanghu Wang, Dachen Zhou, Xiuwei Wu, Mingzhu Gao, Jinjin Wu, Yucai Yang, Xiaoxi Pan, Nianfei Wang","doi":"10.1080/09553002.2024.2373746","DOIUrl":"10.1080/09553002.2024.2373746","url":null,"abstract":"<p><strong>Purpose: </strong>This comprehensive review aims to provide a unique clinical perspective on the latest advances and ongoing boron neutron capture therapy (BNCT) trials for various cancers.</p><p><strong>Methods: </strong>We critically analyzed clinical data from BNCT trials for head and neck cancer, glioblastoma, melanoma, meningioma, breast cancer, and liver tumors. We investigated differences in tumor responses and normal tissue toxicities among trials and discussed potential contributing factors. We also identified the limitations of early BNCT trials and proposed strategies to optimize future trial design.</p><p><strong>Results: </strong>BNCT has shown promising results in treating head and neck cancer, with high response rates and improved survival in patients with recurrent disease. In glioblastoma, BNCT combined with surgery and chemotherapy has demonstrated survival benefits compared to standard treatments. BNCT has also been successfully used for recurrent high-grade meningiomas and shows potential for melanomas, extramammary Paget's disease, and liver tumors. However, differences in tumor responses and toxicities were observed among trials, potentially attributable to variations in treatment protocols, patient characteristics, and evaluation methods.</p><p><strong>Conclusions: </strong>BNCT is a promising targeted radiotherapy for various cancers. Further optimization and well-designed randomized controlled trials are needed to establish its efficacy and safety. Future studies should focus on standardizing treatment protocols and addressing limitations to guide clinical decision-making and research priorities.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1126-1142"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581869","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}
Jorge Ernesto González Mesa, Diego Alem Glison, Fabio Andrés Chaves-Campos, Fernando Ortíz Morales, Luisa Valle Bourrouet, Melissa Abarca Ramírez, Valentina Verdejo, Marina Di Giorgio, Analía Radl, María Rosa Taja, Mayra Deminge, Ana Rada-Tarifa, Erika Lafuente-Alvarez, Fabiana Farias de Lima, Suy Hwang, Mariana Esposito Mendes, Tania Mandina-Cardoso, Gabriela Muñoz-Velastegui, Yolanda Citlali Guerrero-Carbajal, Carolina Arceo Maldonado, Norma Monjagata, Sara Aguilar-Coronel, Marco Espinoza-Zevallos, Aida Falcon de Vargas, Maria Vittoria Di Tomaso, Bret Holladay, Omar García Lima, Wilner Martínez-López
{"title":"LBDNet interlaboratory comparison for the dicentric chromosome assay by digitized image analysis applying weighted robust statistical methods.","authors":"Jorge Ernesto González Mesa, Diego Alem Glison, Fabio Andrés Chaves-Campos, Fernando Ortíz Morales, Luisa Valle Bourrouet, Melissa Abarca Ramírez, Valentina Verdejo, Marina Di Giorgio, Analía Radl, María Rosa Taja, Mayra Deminge, Ana Rada-Tarifa, Erika Lafuente-Alvarez, Fabiana Farias de Lima, Suy Hwang, Mariana Esposito Mendes, Tania Mandina-Cardoso, Gabriela Muñoz-Velastegui, Yolanda Citlali Guerrero-Carbajal, Carolina Arceo Maldonado, Norma Monjagata, Sara Aguilar-Coronel, Marco Espinoza-Zevallos, Aida Falcon de Vargas, Maria Vittoria Di Tomaso, Bret Holladay, Omar García Lima, Wilner Martínez-López","doi":"10.1080/09553002.2024.2356556","DOIUrl":"10.1080/09553002.2024.2356556","url":null,"abstract":"<p><strong>Purpose: </strong>This interlaboratory comparison was conducted to evaluate the performance of the Latin-American Biodosimetry Network (LBDNet) in analyzing digitized images for scoring dicentric chromosomes from <i>in vitro</i> irradiated blood samples. The exercise also assessed the use of weighted robust algorithms to compensate the uneven expertise among the participating laboratories.</p><p><strong>Methods: </strong>Three sets of coded images obtained through the dicentric chromosome assay from blood samples irradiated at 1.5 Gy (sample A) and 4 Gy (sample B), as well as a non-irradiated whole blood sample (sample C), were shared among LBDNet laboratories. The images were captured using the Metafer4 platform coupled with the AutoCapt module. The laboratories were requested to perform triage scoring, conventional scoring, and dose estimation. The dose estimation was carried out using either their laboratory calibration curve or a common calibration curve. A comparative statistical analysis was conducted using a weighted robust Hampel algorithm and z score to compensate for uneven expertise in dicentric analysis and dose assessment among all laboratories.</p><p><strong>Results: </strong>Out of twelve laboratories, one had unsatisfactory estimated doses at 0 Gy, and two had unsatisfactory estimated doses at 1.5 Gy when using their own calibration curve and triage scoring mode. However, all doses were satisfactory at 4 Gy. Six laboratories had estimated doses within 95% uncertainty limits at 0 Gy, seven at 1.5 Gy, and four at 4 Gy. While the mean dose for sample C was significantly biased using robust algorithms, applying weights to compensate for the laboratory's analysis expertise reduced the bias by half. The bias from delivered doses was only notable for sample C. Using the common calibration curve for dose estimation reduced the standard deviation (<i>s</i>*) estimated by robust methods for all three samples.</p><p><strong>Conclusions: </strong>The results underscore the significance of performing interlaboratory comparison exercises that involve digitized and electronically transmitted images, even when analyzing non-irradiated samples. In situations where the participating laboratories possess different levels of proficiency, it may prove essential to employ weighted robust algorithms to achieve precise outcomes.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1019-1028"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141177152","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":"Absorption of 5G sub-6 GHz electromagnetic radiation from base station to male reproduction system.","authors":"Jiajin Lin, Jing Li, Guirong Ding","doi":"10.1080/09553002.2024.2347354","DOIUrl":"10.1080/09553002.2024.2347354","url":null,"abstract":"<p><strong>Background: </strong>The impact of electromagnetic radiation from communication on the male reproductive system has emerged as a significant concern in public health. A notable distinction of the 5G sub-6 GHz band, compared to traditional 2G, 3G, and 4G frequency bands, is the inclusion of higher frequency bands. This has raised public concerns regarding the potential effects of these higher frequencies on organisms, particularly their reproductive systems. While it is imperative to investigate the biological effects and potential risks associated with these new frequency bands in laboratory settings, comparing and evaluating differences between various frequency bands remain challenging due to the absence of standardized parameters such as exposure conditions and duration. In contrast, dose assessment offers a simpler and more reliable approach.</p><p><strong>Materials and methods: </strong>The dose assessment method was employed in this study to investigate the risks associated with sub-6 GHz electromagnetic radiation from 5G base stations on the male reproductive system. A classical human body model (Duke) was utilized, and an electromagnetic simulation environment was established based on the actual polarization direction of the exposed base stations and various body postures. This research explored the effects of field direction, posture, public population, and frequency on the specific absorption rate of the reproductive system.</p><p><strong>Results and conclusions: </strong>While maintaining the same level of exposure, a higher frequency results in a reduced dosage on reproductive system. Further analysis reveals that, considering the public exposure threshold, the employment of higher frequency bands in 5G sub-6 GHz does not present a greater dosage on reproductive system compared to lower frequency bands. Consequently, with regard to dosage, there is no need for excessive concern among the general public regarding the impact of electromagnetic radiation emitted by 5G base stations operating below 6 GHz on male reproductive health.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1085-1092"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856883","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}
Sadegh Masoudi, Mehdi Kalani, Ali Alavianmehr, Mohammad Amin Mosleh-Shirazi, Seyed Mohammad Javad Mortazavi, Shirin Farjadian
{"title":"Sequential radiation exposure: uncovering the potential of low dose ionizing radiation in mitigating high dose effects on immune cells.","authors":"Sadegh Masoudi, Mehdi Kalani, Ali Alavianmehr, Mohammad Amin Mosleh-Shirazi, Seyed Mohammad Javad Mortazavi, Shirin Farjadian","doi":"10.1080/09553002.2024.2345107","DOIUrl":"10.1080/09553002.2024.2345107","url":null,"abstract":"<p><strong>Purpose: </strong>The radioadaptive response refers to a phenomenon wherein exposure to a low dose of ionizing radiation (LDIR) can induce a protective response in cells or organisms, reducing the adverse effects of a subsequent higher dose of ionizing radiation (HDIR). However, it is possible to administer the low dose after the challenge dose. This study was conducted to determine the potential mitigating effect of LDIR administered after HDIR on mice immune cells.</p><p><strong>Materials and methods: </strong>Alongside the conventional adaptive response setting, one group of mice was initially exposed to HDIR and subsequently treated with LDIR. Neutrophil activation was done using DHR-reducing assay and cell proliferation was evaluated through CFSE-dilution assay in helper (CD4<sup>+</sup>) and cytotoxic (CD8<sup>+</sup>) T cells. Cytokine production by these T cell subsets was also assessed by intracellular staining using flow cytometry.</p><p><strong>Results: </strong>The results of this study revealed no change in neutrophil function between any of the mice groups compared to the untreated control group. Although significant changes were not detected in the proliferation of CD4<sup>+</sup> T cells, decreased proliferation was observed in stimulated CD8<sup>+</sup> T cells in the HDIR group. In contrast to IFN-ɣ, which showed no evident change in either of the T cell subsets after stimulation, IL-4 was rigorously dropped in stimulated CD4<sup>+</sup> T cells in the HDIR group.</p><p><strong>Conclusions: </strong>In summary, the results of this study indicated that the administration of LDIR to mice before HDIR was not able to reduce the detrimental effects of HDIR in our experimental setting. Instead, we observed a mitigating effect of LDIR when administered after the challenge dose. This suggests that not only the dose and duration but also the order of LDIR relative to HDIR affects its efficacy.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"1009-1018"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082187","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":"Lifetime attributable risks (LARs) of cancer in the fetus associated with maternal radiography examinations.","authors":"Asra Sadat Talebi, Roghiyeh Bodaghi, Saeed Bagherzadeh","doi":"10.1080/09553002.2023.2295294","DOIUrl":"10.1080/09553002.2023.2295294","url":null,"abstract":"<p><strong>Purpose: </strong>For various reasons, pregnant women are occasionally exposed to ionizing radiation during radiology examinations. In these situations, it is essential to determine the radiation dose to the fetus and any associated risks. The present study attempts to calculate the mean dose for the fetus to estimate the possible cancer induction and cancer mortality risks resulting from maternal radiography exams.</p><p><strong>Material and methods: </strong>The GATE Monte Carlo platform and a standard voxelized pregnant phantom were employed to calculate fetal radiation dose during maternal radiography exams. The data published in Biological Effects of Ionizing Radiation VII were used to convert fetal dose to lifetime attributable risks (LARs) of cancer incidence and cancer-related mortality.</p><p><strong>Results: </strong>The fetal doses and LARs of cancer incidence and cancer-related mortality for the radiographs of the chest and skull were negligible. The maximum LAR values for the lateral view of the abdomen in computed and digital radiography are 5598.29 and 2238.95 per 100,000 individuals, respectively. The computed radiography of the lateral view of the abdomen revealed the highest LAR of cancer-related mortality (2074.30 deaths for every 100,000 people).</p><p><strong>Conclusion: </strong>The radiation dose incurred by the fetus due to chest and skull radiographs was minimal and unlikely to cause any abnormalities in the fetus. The discernible elevation in the lifetime attributable risk associated with cancer incidence and mortality arising from lateral computed radiography examinations of the abdomen warrants careful consideration within the realm of maternal radiography examinations.</p>","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"420-426"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139405673","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}
Daniel Schwanke, Marco Valente, Patrick Ostheim, Simone Schüle, Laure Bobyk, Michel Drouet, Diane Riccobono, Nicolas Magné, Elisabeth Daguenet, Samantha Jo Stewart, Razan Muhtadi, Matthias Port, Michael Abend
{"title":"Validation of genes for H-ARS severity prediction in leukemia patients - interspecies comparison, challenges, and promises.","authors":"Daniel Schwanke, Marco Valente, Patrick Ostheim, Simone Schüle, Laure Bobyk, Michel Drouet, Diane Riccobono, Nicolas Magné, Elisabeth Daguenet, Samantha Jo Stewart, Razan Muhtadi, Matthias Port, Michael Abend","doi":"10.1080/09553002.2023.2295295","DOIUrl":"10.1080/09553002.2023.2295295","url":null,"abstract":"<p><strong>Purpose: </strong>In a previous baboon-study, a total of 29 genes were identified for clinical outcome prediction of the hematologic, acute, radiation, syndrome (H-ARS) severity. Among them, four genes (<i>FDXR, DDB2, POU2AF1, WNT3)</i> appeared promising and were validated in five leukemia patients. Within this study, we sought further in-vivo validation in a larger number of whole-body irradiated patients.</p><p><strong>Material and methods: </strong>Peripheral blood was drawn from 10 leukemia patients before and up to 3 days during a fractionated (2 Gy/day) total-body irradiation (TBI) with 2-12Gy. After RNA-isolation, gene expression (GE) was evaluated on 31 genes widely used in biodosimetry and H-ARS prediction employing qRT-PCR. A customized low-density-array (LDA) allowed simultanously analyzing all genes, the 96-well format further examined the four most promising genes. Fold-changes (FC) in GE relative to pre-irradiation were calculated.</p><p><strong>Results: </strong>Five patients suffering from acute-lymphoblastic-leukemia (ALL) respectively non-Hodgkin-lymphoma (NHL) revealed sufficient RNA-amounts and corresponding lymphocyte and neutrophile counts for running qRT-PCR, while acute-myeloid-leukemia (AML) and one myelofibrosis patient could not supply enough RNA. Generally, 1-2µg total RNA was isolated, whereas up to 10-fold differences in RNA-quantities (associated suppressed GE-changes) were identified among pre-exposure and exposure samples. From 31 genes, 23 were expressed in at least one of the pre-exposure samples. Relative to pre-exposure, the number of expressed genes could halve at 48 and 72h after irradiation. Using the LDA, 13 genes were validated in human samples. The four most promising genes (vid. sup.) were either undetermined or too close to pre-exposure. However, they were measured using the more sensitive 96-well format, except <i>WNT3,</i> which wasn´t detectable. As in previous studies, an opposite regulation in GE for <i>FDXR</i> in leukemia patients (up-regulated) relative to baboons (down-regulated) was reconfirmed. Radiation-induced GE-changes of <i>DDB2</i> (up-regulated) and <i>POU2AF1</i> (down-regulated) behaved similarly in both species. Hence, 16 out of 23 genes of two species showed GE-changes in the same direction, and up-regulated <i>FDXR</i> as in human studies were revalidated.</p><p><strong>Conclusion: </strong>Identified genes for H-ARS severity prediction, previously detected in baboons, were validated in ALL but not in AML patients. Limitations related to leukemia type, associated reduced RNA amounts, suppressed GE changes, and methodological challenges must be considered as factors negatively affecting the total number of validated genes. Based on that, we propose additional controls including blood cell counts and preferably fluorescence-based RNA quantity measurements for selecting promising samples and using a more sensitive 96-well format for candidate genes with low baseline copy","PeriodicalId":94057,"journal":{"name":"International journal of radiation biology","volume":" ","pages":"527-540"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139473078","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}