Tsutomu Shimura, Honoka Nara, Mayu Yamazaki, Megumi Sasatani, Akira Ushiyama
{"title":"Suppression of cancer stem-like cell radioresistance by inhibiting AMPK signaling.","authors":"Tsutomu Shimura, Honoka Nara, Mayu Yamazaki, Megumi Sasatani, Akira Ushiyama","doi":"10.1093/jrr/rraf015","DOIUrl":"10.1093/jrr/rraf015","url":null,"abstract":"<p><p>Cancer stem cell (CSC) radioresistance is a major cause of radiotherapy (RT) failure and tumor recurrence. The molecular target for eradicating CSCs has not been identified despite research efforts to overcome tumor radioresistance. The adenosine monophosphate-activated protein kinase (AMPK) is responsible for transmitting nuclear DNA damage signals to the mitochondria, which in turn generate adenosine triphosphate to execute a DNA damage response. Disruption of this mitochondria-mediated genomic defense mechanism may be an effective strategy to enhance the cytotoxic efficacy of RT. Here, we investigated the potential efficacy of the pan-AMPK inhibitor dorsomorphin (Dor) in preventing CSC radioresistance. Radioresistant cancer stem-like cells were derived from the human liver cancer cell line HepG2 (HepG2 82FR-31NR). The radiosensitizing effect of Dor was then examined in HepG2 82FR-31NR cell cultures by clonogenic assays. Low-dose Dor markedly suppressed the recovery of HepG2 cancer stem-like cells after radiation but had little effect on normal fibroblast proliferation and survival, whether applied alone or in combination with radiation. In conclusion, this study strongly suggests that Dor treatment can radiosensitize cancer stem-like cells at doses that have no significant cytotoxic effects on normal human fibroblasts.</p>","PeriodicalId":16922,"journal":{"name":"Journal of Radiation Research","volume":" ","pages":"227-233"},"PeriodicalIF":1.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Optimizing dwell time weight for interstitial needles in intracavitary/interstitial hybrid brachytherapy: balancing tumor coverage with organ sparing using the inverse planning technique.","authors":"Jun Takatsu, Naoya Murakami, Noriyuki Okonogi, Tatsuya Inoue, Kotaro Iijima, Yoichi Muramoto, Yasuo Kosugi, Terufumi Kawamoto, Tatsuki Karino, Yasuhisa Terao, Naoto Shikama","doi":"10.1093/jrr/rraf025","DOIUrl":"10.1093/jrr/rraf025","url":null,"abstract":"<p><p>The recommended dwell time weight of the needle in intracavitary/interstitial hybrid brachytherapy (HBT) has been 10-20%. This study aimed to investigate the correlation between the weight constraint of the needle and normal organ doses in uterine cervical cancer HBT. This study included 30 cervical cancer patients who received HBT with tandem/ovoid applicators. In our clinical practice, treatment plans were generated without the constraint of the dwell time weight of the needle. The cases where this weight exceeded 20% were replanned. An inverse planning technique with locking downscaled needle dwell time was used to reproduce isodose lines of clinical plans. Replanning repeated with downscaling of the dwell time until the weight of the needle fell <20% (Needle-Lock plan). The Needle-Lock plans were rescaled to coincide with the high-risk clinical target volumes D90 of clinical plans. D2cc in normal organs and the overdose area >200% of the prescribed dose were evaluated. In 17 of 30 (56.7%) clinical plans, the weight of the needle exceeded 20%. The rectum, bladder and sigmoid colon D2cc significantly increased with the Needle-Lock plan. The overdosage area also increased significantly (P < 0.01). The correlations between the needle number and the increase of D2cc in the rectum and sigmoid colon (P < 0.01) were statistically significant. Limiting needle dwell time weight by 10-20% increased bladder and rectum doses, especially with multiple needles. These findings suggest that needle dwell time weight recommendations could need to be reconsidered based on individual and institutional situation.</p>","PeriodicalId":16922,"journal":{"name":"Journal of Radiation Research","volume":" ","pages":"296-305"},"PeriodicalIF":1.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Survival outcomes and prognostic factors in bladder cancer treated with radiotherapy.","authors":"Koyo Kikuchi, Ibuki Ota, Takafumi Segawa, Yoshiro Ieko, Hirobumi Oikawa, Ryuji Nakamura, Hisanori Ariga","doi":"10.1093/jrr/rraf018","DOIUrl":"10.1093/jrr/rraf018","url":null,"abstract":"<p><p>This study evaluated survival outcomes and prognostic factors in patients with bladder cancer treated with radiotherapy. A retrospective analysis was conducted on 488 patients across all cancer stages who received radiotherapy at two institutions between 1 January 2000 and 31 December 2022. Overall survival (OS) was assessed based on treatment intent (radical or palliative) and cancer stage. Among these patients, 304 with Stage II-III disease who underwent radical radiotherapy were further analyzed for OS and prognostic factors using Kaplan-Meier methods and Cox regression analysis. In the radical radiotherapy group, median survival times (MSTs) were 43 months for Stage 0-I, 29 months for Stage II-III, and 17 months for Stage IV (M0). In the palliative radiotherapy group, MSTs were 16 months (95% confidence interval [CI]: 11-25) for M0 and 9 months (95% CI: 7-15) for M1. Among the 304 patients with Stage II-III disease treated with radical radiotherapy, the 3-year OS rate was 43.0%. Hydronephrosis was the only independent prognostic factor significantly associated with worse OS (hazard ratio: 1.915, P < 0.001). Age, sex, stage, treatment era, prophylactic pelvic radiotherapy, chemotherapy and prescribed dose had no significant impact on OS. Radiotherapy remains a viable treatment option for patients at any stage of cancer. Although hydronephrosis negatively affects survival, it should not preclude the use of radiotherapy.</p>","PeriodicalId":16922,"journal":{"name":"Journal of Radiation Research","volume":" ","pages":"272-279"},"PeriodicalIF":1.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yoon Seok Jeong, Kyoung Jin Lee, Yeon Ju Kim, Seung Jin Lee, Woong Sub Koom, Ik Jae Lee, Kyung Hwan Kim
{"title":"Investigating tumor immunogenicity as a determinant of differential abscopal effects.","authors":"Yoon Seok Jeong, Kyoung Jin Lee, Yeon Ju Kim, Seung Jin Lee, Woong Sub Koom, Ik Jae Lee, Kyung Hwan Kim","doi":"10.1093/jrr/rraf021","DOIUrl":"10.1093/jrr/rraf021","url":null,"abstract":"<p><p>This study investigated the role of tumor immunogenicity in the ionizing radiation (IR)-induced abscopal effect. The ovalbumin-expressing B16 cell line (B16-OVA) served as a relatively immunogenic tumor model compared to the B16F10 cell line. C57BL/6 mice were implanted with B16-OVA or B16F10 in the left thigh as the primary tumor and B16F10 in the right thigh as the secondary tumor to evaluate the abscopal response. IR was applied solely to the primary tumor, followed by administration of isotype or anti-programmed cell death protein-1 (PD-1) antibodies. Tumor-infiltrating immune cells were analyzed using flow cytometry. B16-OVA tumors exhibited increased T-cell infiltration and elevated granzyme B and Ki-67 expression in CD8+ T cells compared to B16F10 tumors. IR delayed secondary tumor growth in B16-OVA-irradiated mice, but not in B16F10-irradiated mice. While CD8+ T-cell numbers increased in the secondary tumors of both groups, regulatory T cells significantly increased only in B16F10-irradiated mice. IR promoted differentiation from stem-like TCF1+TIM3- to effector-like TCF1-TIM3+ CD8+ T cells, with elevated granzyme B expression. Polyfunctional T cells co-expressing IFN-γ, TNF-α and IL-2 were significantly increased only in secondary tumors of B16-OVA-irradiated mice under PD-1 blockade. The abscopal effect was abolished by FTY720 treatment and CD8+ T-cell depletion. In conclusion, the IR-induced abscopal effect was dependent on the immunogenicity of the irradiated tumor. The findings may have implication on enhancing abscopal effect in clinical settings.</p>","PeriodicalId":16922,"journal":{"name":"Journal of Radiation Research","volume":" ","pages":"253-263"},"PeriodicalIF":1.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Contouring atlas and essential points for radiotherapy in rectal cancer.","authors":"Keiko Nemoto Murofushi, Kayoko Tsujino, Yoshinori Ito, Masahiko Okamoto, Hiroshi Doi, Hirofumi Ogawa, Masakatsu Onozawa, Terufumi Kawamoto, Norio Katoh, Keiichi Jingu, Atsuya Takeda, Keiji Nihei, Hirokazu Makishima, Hiroshi Mayahara, Hideya Yamazaki, Hiroshi Igaki","doi":"10.1093/jrr/rraf013","DOIUrl":"10.1093/jrr/rraf013","url":null,"abstract":"<p><p>In the last decade, the role of radiotherapy in rectal cancer has changed significantly with the introduction of total neoadjuvant therapy (TNT) and nonoperative management (NOM). For the setting of irradiation field in rectal cancer, the pararectal, lateral lymph nodes, and those along the inferior mesenteric artery (IMA) are most important. In total mesorectal excision (TME), the root of the IMA is dissected. In the atlas of pelvic irradiation for rectal cancer, the setting of the upper margin of the mesorectum varies from atlas to atlas, and no atlas sets the upper margin of the mesorectum to the root of the IMA. In particular, there is no consensus on the definition of anatomical boundaries regarding the lymph nodes along the superior rectal artery (SRA). The upper margin of the irradiation field in clinical trials of preoperative radiotherapy and TNT is generally set at the level of the internal and external iliac artery branches, L5/S1, or S2/S3. However, it is not necessary to include the entire mesorectum to the root of the IMA in patients undergoing preoperative radiotherapy plus TME. Conversely, for patients receiving NOM, the irradiation field may have to include the mesorectum to the IMA root, though the incidence of lymph node metastasis and gastrointestinal adverse events merits consideration. It is increasingly important to determine the extent of clinical target volume around the SRA region and the setting of the upper margin of the irradiation field after formulating the treatment policy together with the surgeons and medical oncologists.</p>","PeriodicalId":16922,"journal":{"name":"Journal of Radiation Research","volume":" ","pages":"203-211"},"PeriodicalIF":1.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regional disparities in IMRT utilization in Japan: analysis of trends and associated medical resources from 2015 to 2019†.","authors":"Keisuke Tamari, Yuna Kumoyama, Hodaka Numasaki, Yuichi Akino, Kazuhiko Hayashi, Takero Hirata, Shotaro Tatekawa, Yutaka Takahashi, Shinichi Shimizu, Kazuhiko Ogawa","doi":"10.1093/jrr/rraf024","DOIUrl":"10.1093/jrr/rraf024","url":null,"abstract":"<p><p>Intensity-modulated radiation therapy (IMRT) uses intensity-modulated photon beams from multiple directions to achieve conformal dose delivery to a target with a complex shape while reducing the dose to organs at risk. We analyzed the trends in IMRT utilization rates across Japanese prefectures from 2015 to 2019 and investigated their relationship with medical resources. Data from the National Database of Health Insurance Claims and the Japanese Society for Radiation Oncology Structure Survey were analyzed. IMRT utilization rates and medical resources (radiation oncologists, medical physicists, radiation technologists, and IMRT-capable linear accelerators) were assessed for all 47 prefectures. A mixed-model analysis was employed to examine the relationship between IMRT utilization rates and medical resources. IMRT utilization increased from 16.4% in 2015 to 22.0% in 2019, with significant regional disparities (range, <10% to >30%). Mixed-model analysis revealed that the number of IMRT-capable linear accelerators (estimate = 0.073, P < 0.01) and radiation oncologists (estimate = 0.032, P = 0.04) was significantly associated with higher IMRT utilization rates. Medical physicists and radiation technologists showed no significant association with IMRT utilization rates. Although the use of IMRT has increased in Japan, substantial regional disparities persist. Increasing the number of IMRT-capable linear accelerators and radiation oncologists may be the most effective strategy to improve equitable access to IMRT in Japan.</p>","PeriodicalId":16922,"journal":{"name":"Journal of Radiation Research","volume":" ","pages":"290-295"},"PeriodicalIF":1.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identifying radiation-induced symptoms from an interview survey.","authors":"Kenichi Yokota, Mariko Mine, Noboru Takamura, Yasushi Miyazaki","doi":"10.1093/jrr/rraf014","DOIUrl":"10.1093/jrr/rraf014","url":null,"abstract":"<p><p>Studies on the atomic bomb have reported a relatively high incidence of acute symptoms, even at below the threshold dose of radiation, and are therefore assumed to include symptoms caused by non-radiation factors. In this study, to investigate the influence of external injuries and burns on symptom expression and the possibility of distinguishing radiation-induced symptoms, we reanalysed data from the survey conducted immediately after the atomic bombing of Nagasaki. The adjusted odds ratios (ORs) of radiation per 1 Gy for the occurrence of 16 symptoms ranged from 1.14 to 1.46, based on sex, age at the time of the bombing, radiation dose, external injuries, and burns. This study also included 243 deaths, and thus provides information not seen in other studies, such as the frequency of symptoms in deaths and ORs for symptom occurrence. However, the adjusted ORs for external injuries or burns were smaller than the unadjusted ORs, suggesting that external injuries and burns confound the development of radiation-induced symptoms. Symptom data obtained from interviews such as those used in this study may not be appropriate for use alone because such data include non-radiation factors. Radiation-induced symptoms are often considered to be a syndrome, and the multiple correspondence analyses also revealed that high-dose exposure is associated with nausea and vomiting, subsequent epilation and bleeding tendency as a bone marrow disorder, and inflammation symptoms due to a weakened immune system. Thus, radiation exposure may be indicated by not just one, but rather, a combination of symptoms.</p>","PeriodicalId":16922,"journal":{"name":"Journal of Radiation Research","volume":" ","pages":"212-226"},"PeriodicalIF":1.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparison of carbon ion radiotherapy and transarterial chemoembolization for unresectable solitary hepatocellular carcinoma >3 cm: a propensity score-matched analysis.","authors":"Taito Fukushima, Satoshi Kobayashi, Hiroyuki Katoh, Tomomi Hamaguchi, Yuichiro Tozuka, Yasutsugu Asai, Shun Tezuka, Makoto Ueno, Manabu Morimoto, Junji Furuse, Shin Maeda","doi":"10.1093/jrr/rraf026","DOIUrl":"10.1093/jrr/rraf026","url":null,"abstract":"<p><p>This study aimed to compare outcomes between carbon ion radiotherapy (C-ion RT) and transarterial chemoembolization (TACE) in patients with unresectable solitary hepatocellular carcinoma (HCC) >3 cm. Fifty-eight patients who had been treated with C-ion RT (C-ion RT group) and 34 treated with TACE (TACE group) were retrospectively enrolled between January 2016 and December 2021. Propensity score matching was conducted to account for differences between the two groups. The median follow-up duration was 42.1 months for all patients. Propensity score matching successfully balanced the two groups with 29 patients matched to each group. The 3-year overall survival (OS), progression-free survival (PFS) and local control (LC) rates in the C-ion RT vs TACE groups were 75.9% vs 45.4%, 44.8% vs 16.1% and 85.2% vs 23.2%, respectively. The C-ion RT group showed better OS (hazard ratio [HR], 0.578 [95% confidence interval (CI): 0.295-1.132]; P = 0.106), PFS (HR, 0.460 [95% CI: 0.254-0.835]; P = 0.009) and LC (HR, 0.155 [95% CI: 0.062-0.390]; P < 0.001) than the TACE group. Multivariate analysis indicated that C-ion RT was significantly associated with increased PFS (HR, 0.562 [95% CI: 0.341-0.926]; P = 0.024) and LC (HR, 0.282 [95% CI: 0.150-0.528]; P < 0.001). C-ion RT provided better OS, PFS and LC than TACE in patients with solitary HCC >3 cm. This study indicated that C-ion RT is a possible alternative to TACE, which is the standard of care for patients with medium-to-large-sized HCCs.</p>","PeriodicalId":16922,"journal":{"name":"Journal of Radiation Research","volume":" ","pages":"306-317"},"PeriodicalIF":1.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Improvement of deep learning-based dose conversion accuracy to a Monte Carlo algorithm in proton beam therapy for head and neck cancers.","authors":"Ryohei Kato, Noriyuki Kadoya, Takahiro Kato, Ryota Tozuka, Shuta Ogawa, Masao Murakami, Keiichi Jingu","doi":"10.1093/jrr/rraf019","DOIUrl":"10.1093/jrr/rraf019","url":null,"abstract":"<p><p>This study is aimed to clarify the effectiveness of the image-rotation technique and zooming augmentation to improve the accuracy of the deep learning (DL)-based dose conversion from pencil beam (PB) to Monte Carlo (MC) in proton beam therapy (PBT). We adapted 85 patients with head and neck cancers. The patient dataset was randomly divided into 101 plans (334 beams) for training/validation and 11 plans (34 beams) for testing. Further, we trained a DL model that inputs a computed tomography (CT) image and the PB dose in a single-proton field and outputs the MC dose, applying the image-rotation technique and zooming augmentation. We evaluated the DL-based dose conversion accuracy in a single-proton field. The average γ-passing rates (a criterion of 3%/3 mm) were 80.6 ± 6.6% for the PB dose, 87.6 ± 6.0% for the baseline model, 92.1 ± 4.7% for the image-rotation model, and 93.0 ± 5.2% for the data-augmentation model, respectively. Moreover, the average range differences for R90 were - 1.5 ± 3.6% in the PB dose, 0.2 ± 2.3% in the baseline model, -0.5 ± 1.2% in the image-rotation model, and - 0.5 ± 1.1% in the data-augmentation model, respectively. The doses as well as ranges were improved by the image-rotation technique and zooming augmentation. The image-rotation technique and zooming augmentation greatly improved the DL-based dose conversion accuracy from the PB to the MC. These techniques can be powerful tools for improving the DL-based dose calculation accuracy in PBT.</p>","PeriodicalId":16922,"journal":{"name":"Journal of Radiation Research","volume":" ","pages":"280-289"},"PeriodicalIF":1.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Erin Wallisch, Aoy Tomita-Mitchell, Huan-Ling Liang, Aniko Szabo, Marek Lenarczyk, Anne Kwitek, Jennifer R Smith, Monika Tutaj, John E Baker
{"title":"Advancing cell-free DNA as a biomarker of damage to heart caused by ionizing radiation.","authors":"Erin Wallisch, Aoy Tomita-Mitchell, Huan-Ling Liang, Aniko Szabo, Marek Lenarczyk, Anne Kwitek, Jennifer R Smith, Monika Tutaj, John E Baker","doi":"10.1093/jrr/rraf022","DOIUrl":"10.1093/jrr/rraf022","url":null,"abstract":"<p><p>Exposure to diagnostic and therapeutic radiation introduces risks for development of diseases later in life by causing DNA damage in cells. Currently, there is no clinical method for determining exposure risk caused by radiation toxicity to DNA. Cell-free DNA (cfDNA), a marker of DNA damage, is currently used to assess risk for long-term effects following organ transplantation, surgery and inflammation. The goal of our proposed study is to develop cfDNA as an early biomarker for assessing risk for cardiovascular disease and cancer from radiation exposure so that strategies to mitigate the damaging effects of medical radiation can be assessed. Hearts from male and female WAG/RijCmcr rats (n = 6-10/group) were exposed to increasing doses of X-radiation (50 mGy and 3.5 Gy). Blood was collected prior to and after (15 minutes-96 hours) irradiation, and cell-free plasma was prepared. Primers and probes were designed for quantitative analysis of sequences of mitochondria (12S rRNA) and nuclear (Gapdh) cfDNA present in rat plasma using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Exposure of hearts to radiation increased nuclear and mitochondrial cfDNA in a dose-dependent manner. Three point five grays from X-radiation increase cfDNA for Gapdh in plasma after 1 hour with a 15.8-fold increase (P < 0.001) after 6 hours. The earliest time nuclear and mitochondrial cfDNA increases were detected in plasma was at 60 minutes following exposure to 3.5 Gy. cfDNA has potential to advance as a biomarker of exposure to medical doses of radiation in patients.</p>","PeriodicalId":16922,"journal":{"name":"Journal of Radiation Research","volume":" ","pages":"329-340"},"PeriodicalIF":1.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}