Radiation research最新文献

{"title":"Changes in Yields of Water Radiolysis Species and Strand Breaks of Pbr322 Plasmid DNA under Ultra-high Dose Rate C Ions: Towards the Elucidation of the Mechanism of FLASH Radiotherapy.","authors":"Taisei Mamiya, Koki Kasamatsu, Taku Inaniwa, Kazuyoshi Kurita, Satoshi Kodaira, Teruaki Konishi, Tamon Kusumoto","doi":"10.1667/RADE-25-00210.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00210.1","url":null,"abstract":"<p><p>To clarify the mechanisms of FLASH radiotherapy using C ion beams (373 MeV/u and 90 MeV/u), we investigated the dose rate dependence of yields of water radiolysis species (OH radicals, hydrated electrons, and hydrogen peroxide). Additionally, we evaluated changes in the induction rate of DNA strand breaks as a function of dose rate using pBR322 plasmid DNA in solutions. Average dose rates were 0.2 Gy/s [conventional (CONV)] and 75 Gy/s [ultra-high dose rate (UHDR)] for 373 MeV/u, and 0.3 Gy/s (CONV) and 100 Gy/s (UHDR) for 90 MeV/u. The G values of water radiolysis species decreased with UHDR irradiation compared to CONV dose rate, except for hydrogen peroxide exposed to 90 MeV/u C ions, whose yield remained independent of dose rate. Furthermore, the induction rate of single-strand breaks (SSB) was unaffected by dose rate, while the induction of double-strand breaks (DSB) decreased after UHDR irradiation. These findings suggest that radical-radical reactions occur more efficiently with increasing dose rate, resulting in a reduced contribution of water radiolysis species to DNA strand breaks, especially DSBs, after irradiation with C ions. Therefore, changes in the contribution of water radiolysis species to DNA strand breaks could play a crucial role in the sparing effects observed after UHDR irradiation.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456569","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":"Chronic Inflammation in Irradiated Mouse Mammary Glands: A Transcriptome Sequencing Analysis.","authors":"Xiaoran Shi, Junyang Chen, Zhongshuang Liu, Baoxu Li, Weimin Jiang, Yiyuan Liang, Lu Wen, Yonghui Luo, Yupeng Luo, Anhui Wu, Rui Fu, Qi Liu, Lin Ma","doi":"10.1667/RADE-25-00181.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00181.1","url":null,"abstract":"<p><p>Normal tissues exposed to radiation during radiotherapy or radiation accidents are susceptible to chronic inflammation, which poses a significant health concern. Here, we used the mouse mammary gland as a model to investigate radiation-induced damage to normal tissue. Five-week-old mice were chosen to capture the radiation-sensitive pubertal developmental window, and transcriptomic sequencing was used to profile gene expression changes at 1-5 months postirradiation. Single-cell RNA sequencing was performed to identify immune cell populations and characterize their transcriptional features at the subpopulation level. By combining transcriptomic data with morphological analysis of the irradiated mammary gland, we identified gene expression signatures of specific macrophage and T cell subtypes within the postirradiation microenvironment and highlighted their roles in modulating inflammation and maintaining cell junction homeostasis. Notably, dysregulation of adipocyte differentiation and lipid metabolism pathways was observed as early as 1 month postirradiation, and this metabolic disturbance was associated with persistently elevated oxidative stress in the tissue. Single-cell analysis showed that CD163+ macrophages were functionally enriched in lipid metabolism pathways, and immunofluorescence staining confirmed their significant accumulation in the irradiated mammary gland. Overall, these findings suggest that CD163+macrophages are key mediators of chronic tissue inflammation after irradiation. This study offers a comprehensive characterization of microenvironmental changes in the irradiated mammary gland and identifies potential targets for radioprotection strategies to modulate tissue microenvironment factors.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456583","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":"Effects of Partial-body, Continuous/Pulse Irradiation at Dose Rates from Flash to Conventional Rates on the Level of Surviving Blood Lymphocytes: Modeling Approach. III. Lymphocyte Survival Is a Biomarker of Flash Sparing Effects.","authors":"Francis A Cucinotta, Olga A Smirnova","doi":"10.1667/RADE-25-00134.1","DOIUrl":"10.1667/RADE-25-00134.1","url":null,"abstract":"<p><p>Experimental data on magnitudes of sparing effects of whole-abdominal pulse irradiation, whole-brain pulse irradiation, and bilateral thorax pulse/continuous irradiation at high doses and dose rates from conventional to FLASH irradiation rates (> 40 Gy/s) on normal intestinal, brain, and lung tissues in mice, which were reported in the literature, are analyzed by making use of recently developed mathematical models. These models are capable of predicting the fractions of surviving blood lymphocytes in mice after the exposures. Results of juxtaposing those experimental data with the respective modeling results suggest a possible relationship between them. Recent experimental findings confirming this relationship are presented. Finally, an algebraic formula to predict FLASH dose rate thresholds for the exposures is derived and verified, providing a tool for future experimental design.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"337-347"},"PeriodicalIF":2.4,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148423418","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":"KRT6A Impairs Radiosensitivity in Cervical Squamous Cell Carcinoma by Enhancing Fatty Acid Synthesis.","authors":"Manping Zha, Yanli Du","doi":"10.1667/RADE-25-00242.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00242.1","url":null,"abstract":"<p><p>Cervical squamous cell carcinoma (CESC), a subtype of cervical cancer, is an aggressive cancer. Radiotherapy is a key treatment for locally advanced cases, but its success is often limited by radioresistance. Therefore, this study explores whether the intermediate filament protein KRT6A increases the radioresistance of CESC cells by regulating lipid metabolism. The expression profile of KRT6A was analyzed using the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets via the University of California Santa Clara UCSC Xena platform, while associated signaling pathways were identified through gene set enrichment analysis (GSEA) based on the GSE44001 dataset. Radioresistant SiHa cells (SiHa-R) were developed from the parental human CESC SiHa cell line. KRT6A mRNA levels were measured by qRT-PCR. Protein expression of KRT6A, γH2AX, and key lipogenic enzymes fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC1) was detected through Western blotting. Cell viability and proliferation were assessed using CCK-8 and colony formation assays, respectively. Apoptosis was evaluated with Annexin V-FITC/PI staining. Lipogenesis was examined by BODIPY staining and Acetyl-CoA measurement. Fatty acid composition was analyzed using liquid chromatography-mass spectrometry (LC-MS). KRT6A was found to be upregulated in CESC tissues compared to normal tissues and was further increased in radioresistant cells compared to radiosensitive cells. Its knockdown in radioresistant SiHa cells reduced cell viability and proliferation, increased apoptosis, and enhanced radiation-induced DNA damage. GSEA indicated KRT6A's involvement in fatty acid metabolism. LC-MS analysis showed that reducing KRT6A expression led to the overall decrease in multiple fatty acids. Overexpression of KRT6A increased FASN and ACC1 levels, promoted lipid droplet formation, and decreased radiation damage. These resistance effects were effectively reversed by the lipogenesis inhibitor C75. Therefore, KRT6A promotes radioresistance in CESC by activating lipogenesis.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369828","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":"Chromosomal Instability: A Potential Biomarker of Radiation Response.","authors":"Nikki N Messick, Yeseo Choi, Dingtong Tan, Francesca J Scribano, Beth A Weaver, Pippa F Cosper","doi":"10.1667/RADE-26-00093.1","DOIUrl":"10.1667/RADE-26-00093.1","url":null,"abstract":"<p><p>Radiotherapy is a widely used cancer treatment modality with more than 70% of head and neck cancer (HNC) patients receiving it in either the definitive or adjuvant settings. Currently, all HNC patients, regardless of human papillomavirus (HPV) status, are treated with the same radiation dose, yet treatment response remains highly variable across patients and radiation-induced treatment toxicities continue to pose significant clinical challenges. To date, there are no clinically approved methods or biomarkers that can predict patient response to radiation, hindering the development of personalized radiation treatment strategies. In our recent publication in the International Journal of Radiation Oncology, Biology, Physics (1), we approached this clinical problem by focusing on a biological characteristic occurring in nearly all cancer cells to different degrees; chromosomal instability (CIN). CIN is defined as an ongoing rate of chromosome missegregation events over consecutive cell divisions, and is a type of genomic instability, which is a hallmark of cancer. One consequence of CIN is aneuploidy, or a state of abnormal chromosome content. It is important to distinguish CIN from aneuploidy as we discovered it is the rate of chromosome missegregation during mitosis (CIN) that determines cell fate after radiation.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"270-273"},"PeriodicalIF":2.4,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346210","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":"Antioxidant Probucol Reduces Mortality in Mice Exposed to Lethal Doses of Ionizing Radiation.","authors":"Shunsuke Tanigawa, Ki-Ichiro Kawano, Nobuyuki Hamada, Farina Mohamad Yusoff, Asuka Fujita, Tatsuya Maruhashi, Masato Kajikawa, Shinji Kishimoto, Takayuki Yamaji, Aya Mizobuchi, Ayumu Nakashima, Yukihito Higashi","doi":"10.1667/RADE-26-00251.1","DOIUrl":"10.1667/RADE-26-00251.1","url":null,"abstract":"<p><p>Radiation has beneficial medical and industrial applications; however, high-dose exposure during accidents can result in severe outcomes, including fatal bone marrow failure. Total-body irradiation (TBI) of 6-10 Gy induces hematopoietic failure, primarily due to oxidative stress caused by excessive reactive oxygen species. This study aimed to evaluate the protective potential of probucol, a potent antioxidant, against lethal ionizing radiation-induced damage. Eight-week-old mice received 8 Gy TBI. Two probucol treatment strategies were tested: pretreatment, in which the drug was administered daily for 4 days before irradiation, and post-treatment, in which the drug was administered 4 h after irradiation and continued for 4 days. Survival rates, peripheral blood cell counts, bone marrow and spleen morphology, and urinary excretion levels of 8-hydroxy-2'-deoxyguanosine (oxidative DNA damage) were analyzed. Probucol pretreatment improved survival in mice that received 8 Gy TBI, whereas most of the mice in the post-treatment group and all of the mice in vehicle control group died within 30 days after exposure. Probucol pretreatments also significantly decreased the urinary excretion of 8-hydroxy-2'-deoxyguanosine compared with untreated control mice. Although TBI caused pancytopenia in both groups, peripheral blood cell counts showed no difference between the groups on day 14 postirradiation. Probucol pretreatment preserved nucleated bone marrow cells and showed extramedullary hematopoiesis in the spleen. These findings suggest that probucol pretreatment exert beneficial effects by mitigating radiation-induced bone marrow suppression and promoting compensatory extramedullary hematopoiesis within the spleen through its antioxidative action.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"284-291"},"PeriodicalIF":2.4,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148309185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Detection of Radiation Effects in the Urine of Rhesus Macaques Using Raman Spectroscopy.","authors":"Courtney S Moore, Amr Sayed Issa, Lacey Ngo, Johann Hsu, J Mark Cline, Ryan S Senger, John L Robertson","doi":"10.1667/RADE-25-00162.1","DOIUrl":"10.1667/RADE-25-00162.1","url":null,"abstract":"<p><p>Exposure to ionizing radiation has been associated with the development of neoplasms in humans and other animals. Detection of both neoplastic growth and effects of radiation with standard laboratory testing (hematology and serum chemistry analyses) is problematic. There are no specific biomarkers present in biological fluids (blood, urine) for early detection of neoplastic growth or long-term effects of radiation exposure, but these would be extremely useful for monitoring both treatment efficacy and detecting undesirable side effects in patients undergoing radiotherapy. We conducted a retrospective study of 76 urine samples from rhesus macaques using a novel Raman spectroscopy-based analytical technology (Raman Molecular Urinalysis) to establish a urine fingerprint for past radiation treatment. Forty-nine animals were irradiated (of which 12 developed sarcomas following experimental exposure to total body ionizing radiation) and 27 animals were not irradiated (2 of which developed non-radiation-associated sarcomas). We applied an unsupervised principal component analysis and supervised discriminant analysis of principal components and averaged the spectra. The results showed the groups had a highly similar average spectra, but more variability and outliers existed in the irradiated group of animals. The unique characteristics of these outliers were unclear, and further investigation is needed. Animals with sarcomas had a distinct spectral profile with high specificity and high negative predictive value. A definitive radiation molecular spectral fingerprint was not identified in the urine of irradiated macaques in comparison to unirradiated control animals, but this study provides initial evidence and insights for future research.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"292-299"},"PeriodicalIF":2.4,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148278473","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":"Characterization of Radiation-responsive Genes and Transcript Variants under Different Radiation Qualities, Doses and Dose Rates.","authors":"Maria Polozova, Lourdes Cruz-Garcia, Shanaz A Ghandhi, Salan Preet Kaur, Guy Garty, Naresh Deoli, Andrew Harken, Helen C Turner, Veronika Goriacha, Christophe Badie","doi":"10.1667/RADE-26-00035.1","DOIUrl":"10.1667/RADE-26-00035.1","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Rapid molecular biodosimetry may support radiation exposure assessment during mass casualty or mixed-field radiological incidents, but how gene expression responses vary across radiation qualities and dose rates remains incompletely characterized. Gene expression biodosimetry, including transcript-variant-aware measurements resulting from alternative splicing, may improve sensitivity for determining radiation quality and dose rate. We profiled nine radiation-responsive genes (AEN, APOBEC3H, DDB2, EDA2R, FDXR, PCNA, RPS27L, TRIAP1, ZMAT3) and six FDXR transcript variants using custom 384-well microfluidic RT-qPCR array cards (TaqMan Low Density Array, TLDA) of ex vivo leukopak-derived samples (leukocyte-enriched blood products) from three healthy donors, harvested 24 h after irradiation. Samples received an acute exposure of X rays (0.1-4 Gy), a protracted exposure of X rays (2 Gy at 0.1, 0.01, 0.004 Gy·min-1), and a mixed neutron field exposure with approximately 81% neutrons and 19% concomitant γ-rays (0.1-2 Gy at 0.6-1 Gy·h-1). In a separate experiment, gene expression of leukopaks was concordant with whole blood responses for FDXR and CDKN1A, with FDXR exceeding a 30-fold induction after exposure to 4 Gy of X rays. In the TLDA dataset, all targets were upregulated in a dose-dependent manner. Over the range of 0.1-1 Gy, neutrons elicited higher induction than X rays for APOBEC3H, DDB2, and FDXR, with convergence at 2 Gy as X-ray responses plateaued. Variant-level analysis showed isoform-specific behavior: FDXR-203 and FDXR-206 mRNA isoforms were induced by neutrons (especially at higher doses), while FDXR-202, FDXR-205, and FDXR-217 responded preferentially to X rays and FDXR-204 was moderately upregulated after X-ray irradiation. After protracted X-ray exposure, most genes were up-regulated with minimal dose-rate effects; AEN was the only target that differed significantly between 0.004 and 0.01 Gy·min-1, and FDXR-202/-204/-205 showed a higher fold change at the lowest dose rate. Analysis of dose-response behavior and derived relative biological effectiveness (RBE) values revealed three patterns when comparing neutrons with X rays. First, FDXR, DDB2 and EDA2R were more responsive to neutrons than to X rays at low doses (0.1-1 Gy), with fold changes increasing faster for neutrons. Depending on the gene, neutrons were equivalent to X-ray doses that were approximately 2-4 times higher, consistent with results reported previously for cytogenetic endpoints. Second, APOBEC3H, FDXR-217, RPS27L, PCNA and FDXR-203 showed similar dose-response behavior after exposure to neutrons and X rays, with occasional plateau differences. Third, AEN, TRIAP1 and the remaining assayed FDXR variants showed high variability and were not studied further here. Overall, several genes showed little discrimination across low dose rates, supporting their use for estimating total dose, while others showed clear differences between radiations of different qualities. Take","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"311-323"},"PeriodicalIF":2.4,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265878","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":"Methyl Quercetin Inhibits Radiation-induced Senescence and TGF-β1-induced Myofibroblast Differentiation Through psmad3/TGF-β Signaling.","authors":"Heesu Ahn, Eun Joo Chung, Alya White, Hong Zhang, Seokjoo Kwon, Santwana Kc, Deborah E Citrin","doi":"10.1667/RADE-25-00239","DOIUrl":"10.1667/RADE-25-00239","url":null,"abstract":"<p><p>Previously, we demonstrated that continuous oral delivery of quercetin attenuated radiation-induced dermal fibrosis in C3H/HeN mice exposed to 35 Gy of ionizing radiation. Quercetin was rapidly metabolized and primarily detected in plasma, liver, and urine as methylated metabolites. The current study aimed to investigate the biological effects of methylated quercetin on radiation-induced cellular senescence and macrophage polarization, and to evaluate its therapeutic potential for ameliorating radiation-induced skin fibrosis. Skin tissue was collected from C3H/HeN mice fed quercetin-formulated or control chow and exposed to 0 Gy or 35 Gy at 150 days postirradiation. In mice irradiated with 35 Gy, quercetin chow administration reduced epidermis thickness, the number of cells that were positive for senescent markers (p21, p16) positive cells and vimentin-positive cells in the skin, compared with control chow administration. Also, the number of cells positive for macrophage markers (F4/80, CD206) were decreased. These in vivo results were consistent with findings in NIH/3T3 fibroblasts irradiated with either 0 Gy or 17.5 Gy in the presence of 3-O-methylquercetin (MQ) or vehicle. X-gal staining and p21 expression detected by Western blotting indicated that radiation-induced cellular senescence, but it was decreased by pretreatment of MQ. Senescence-associated secretory phenotype (SASP) factors including TGF-β1 and Pai-1 were significantly higher in the irradiated fibroblasts but decreased in the presence of MQ. In addition, MQ pretreatment reduced cell proliferation and vimentin expression via canonical TGF-β1 signaling. Furthermore, conditioned media (CM) from irradiated fibroblasts induced M2 polarization of Raw264.7 macrophages, whereas CM from MQ-treated irradiated fibroblasts decreased M2 macrophage expression. Taken together, these results indicate that MQ is a potential senomorphic agent, reducing SASP expression to mitigate radiation-induced skin senescence and macrophage polarization, and exerting protective effects against radiation-induced skin fibrosis.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"274-283"},"PeriodicalIF":2.4,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148219553","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":"Salivary Gene Expression Changes after Total Body Irradiation in Leukemia Patients: Toward Non-invasive Biodosimetry.","authors":"S Fischer, M Kasper, S Stewart, N Schmid, G O'Brien, O Zahradníček, M Milanová, M Marková Št'astná, I Sirak, R Muhtadi, C Badie, S Eder, M Port, A Tichý, P Ostheim","doi":"10.1667/RADE-25-00218","DOIUrl":"10.1667/RADE-25-00218","url":null,"abstract":"<p><p>Blood is the standard matrix for gene expression (GE)-based biodosimetry, but less invasive sampling methods are needed in emergency settings and for longitudinal monitoring. Saliva, which contains leukocytes and an ultrafiltrate of blood, is a promising alternative. In this human in vivo study, we analyzed radiation-induced shifts in salivary gene expression for biodosimetric applications and evaluated their similarity to gene expression patterns in blood. Beyond dose estimation, such saliva-based gene expression signatures may support risk stratification and early prediction of clinical outcomes, particularly when repeated sampling is required or blood collection is not feasible. Matched blood and saliva samples were collected from leukemia patients (n = 31) undergoing fractionated total-body irradiation (TBI) for their myeloablative treatment (1.5-4 Gy total dose, 1.5-2 Gy per fraction). Samples were taken before and 24 h after the first day of radiation treatment. The expression of radiation-responsive genes (GADD45A, CCNG1, CDKN1A, PHPT1, SESN1, FDXR, DDB2, POU2AF1, and WNT3) was analyzed for 28 patients (three patients excluded) using quantitative real-time PCR (RT-qPCR). Significant upregulation was observed for GADD45A (median fold change = 1.52, P = 0.003), CCNG1 (median fold change = 1.73; P = 0.003), and DDB2 (median fold change = 1.60; P = 0.05), as well as WNT3 (median fold change = 1.84; P = 0.038), demonstrating that saliva shows molecular responses to radiation exposure. Notably, 54% of the patients exhibited radiation-responsive upregulation of GADD45A and CCNG1, indicating that saliva can detect radiation-responsive gene expression despite substantial inter-individual variability. Corresponding blood samples were obtained from 16 patients. Statistically significant upregulation of multiple radiation-responsive genes was observed: GADD45A (median fold change = 2.25; P < 0.001), CCNG1 (median fold change = 1.64; P = 0.010), DDB2 (median fold change = 1.91; P < 0.001), CDKN1A (median fold change = 2.45; P = 0.001), SESN1 (median fold change = 1.75; P < 0.001), and FDXR (median fold change = 2.53; P = 0.001). A significant downregulation was observed for POU2AF1 (median fold change = 0.49; P = 0.013). In conclusion, detection of radiation-induced gene expression changes in saliva may serve as a minimally invasive tool for biodosimetry. However, given the greater inter-individual variability observed in saliva compared to blood, further optimization and validation is essential before clinical implementation.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":"186-196"},"PeriodicalIF":2.4,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148157518","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}