Radiation research最新文献

{"title":"Relative Biological Effectiveness of Carbon Ion Beams for Induction of Medulloblastoma with Radiation-specific Chromosome 13 Deletion in Ptch1+/- Mice.","authors":"Chizuru Tsuruoka, Mayumi Shinagawa, Yi Shang, Yoshiko Amasaki, Masaaki Sunaoshi, Tatsuhiko Imaoka, Takamitsu Morioka, Yoshiya Shimada, Shizuko Kakinuma","doi":"10.1667/RADE-23-00229.1","DOIUrl":"10.1667/RADE-23-00229.1","url":null,"abstract":"<p><p>Carbon ion radiotherapy (CIRT) for pediatric cancer is currently limited because of the unknown risk of induction of secondary cancers. Medulloblastoma of Ptch1+/- mice offers a unique experimental system for radiation-induced carcinogenesis, in which tumors are classified into spontaneous and radiation-induced subtypes based on their features of loss of heterozygosity (LOH) that affect the wild-type Ptch1 allele. The present study aims to investigate in young Ptch1+/- mice the carcinogenic effect, and its age dependence, of the low-linear energy transfer (LET, ∼13 keV/µm) carbon ions, to which normal tissues in front of the tumor are exposed during therapy. We irradiated Ptch1+/- mice at postnatal day (P) 1, 4, or 10 with 290 MeV/u carbon ions (0.05-0.5 Gy; LET, 13 keV/µm) and monitored them for medulloblastoma development. Loss of heterozygosity of seven genetic markers on chromosome 13 (where Ptch1 resides) was studied to classify the tumors. Carbon ion exposure induced medulloblastoma most effectively at P1. The LOH patterns of tumors were either telomeric or interstitial, the latter occurring almost exclusively in the irradiated groups, allowing the use of interstitial LOH as a biomarker of radiation-induced tumors. Radiation-induced tumors developed during a narrow age window (most strongly at P1 and only moderately at P4, with suppressed tumorigenesis at P10). Calculated using previous results using 137Cs gamma rays, the values for relative biological effectiveness (RBE) regarding radiation-induced tumors were 4.1 (3.4, 4.8) and 4.3 (3.3, 5.2) (mean and 95% confidence interval) for exposure at P1 and 4, respectively. Thus, the RBE of carbon ions for medulloblastoma induction in Ptch1+/- mice was higher than the generally recognized RBE of 1-2 for cell killing, chromosome aberrations, and skin reactions.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760622","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":"Estimating Impacts of p16 Status on Tumor Radiosensitivity in Head and Neck Cancer using Predictive Models.","authors":"Atsushi Kaida, Hitomi Nojima, Masahiko Miura","doi":"10.1667/RADE-24-00066.1","DOIUrl":"10.1667/RADE-24-00066.1","url":null,"abstract":"<p><p>The intrinsic radiosensitivity index (RSI) and genomic-adjusted radiation dose (GARD) were reported to be able to predict the surviving fraction at 2 Gy and therapeutic effect when delivering actual treatment doses using the gene expression profiles of clinical cases. Given the impact of p16 status, a surrogate marker of the human papillomavirus (HPV) infection, on radiosensitivity, we attempted to apply the RSI and GARD to estimate p16-associated radiosensitivity in head and neck squamous cell carcinoma (HNSC). For this purpose, The Cancer Genome Atlas (TCGA) dataset was employed. In the GARD calculation, we assumed that p16-positive patients received 60 Gy in 30 fractions, while p16-negative patients received 70 Gy in 35 fractions. p16 positivity was associated with favorable characteristics compared to negative patients. The RSI and GARD analyses demonstrated increased radiosensitivity and high therapeutic effect in p16-positive patients, compared to p16-negative patients. Additionally, tumor microenvironmental conditions predicted by other models were also significantly affected by p16 status. Collectively, the models used in this study could be a promising tool for estimating p16-associated radiosensitivity in HNSC.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734870","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":"Dimethyl Sulfoxide Attenuates Ionizing Radiation-induced Centrosome Overduplication and Multipolar Cell Division in Human Induced Pluripotent Stem Cells.","authors":"Mikio Shimada, Ryoichi Hirayama, Yoshihisa Matsumoto","doi":"10.1667/RADE-24-00069.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00069.1","url":null,"abstract":"<p><p>Centrosomes are important organelles for cell division and genome stability. Ionizing radiation exposure efficiently induces centrosome overduplication via the disconnection of the cell and centrosome duplication cycles. Over duplicated centrosomes cause mitotic catastrophe or chromosome aberrations, leading to cell death or tumorigenesis. Pluripotent stem cells, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), can differentiate into all organs. To maintain pluripotency, PSCs show specific cellular dynamics, such as a short G1 phase and silenced cell-cycle checkpoints for high cellular proliferation. However, how exogenous DNA damage affects cell cycle-dependent centrosome number regulation in PSCs remains unknown. This study used human iPSCs (hiPSCs) derived from primary skin fibroblasts as a PSC model to address this question. hiPSCs derived from somatic cells could be a useful tool for addressing the radiation response in cell lineage differentiation. After radiation exposure, the hiPSCs showed a higher frequency of centrosome overduplication and multipolar cell division than the differentiated cells. To suppress the indirect effect of radiation exposure, we used the radical scavenger dimethyl sulfoxide (DMSO). Combined treatment with radiation and DMSO efficiently suppressed DNA damage and centrosome overduplication in hiPSCs. Our results will contribute to the understanding of the dynamics of stem cells and the assessment of the risk of genome instability for regenerative medicine.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111408","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":"Harnessing Senescence for Antitumor Immunity to Advance Cancer Treatment.","authors":"Pataje G S Prasanna","doi":"10.1667/RADE-24-00098.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00098.1","url":null,"abstract":"<p><p>Considering the limitations and complexities of the cell-killing-based cancer treatment approaches, one could aim to integrate symbiotic advances in many energy delivery technologies and transformational pieces of evidence in research on senescence and immunomodulators to advance cancer treatment. Although senescent cells contribute to drug tolerance, resistance to therapy, tumorigenesis, maladapting cancer phenotypes, tumor relapse, recurrence, and metastasis, emerging pieces of evidence also demonstrate that acutely induced senescent cells in tumors can elicit a strong and lasting antitumor immune response juxtaposed to the immunologically silent apoptotic cells. This commentary is to help develop an unconventional conceptual framework to advance cancer treatment. Accordingly, it will involve transiently inducing senescent cells in tumors at optimal levels to prime the immune system with radiation, then eliminating senescent cells with senolytics (drugs that specifically eliminate senescent cells) to disrupt their positive feedback accumulation (to prevent tumor maladaptation and adverse effects in healthy cells) and unleash long-lasting antitumor immunity with immunomodulators. The approach is reasonably speculative and will require scientifically rigorous \"fit-for-purpose,\" well-controlled preclinical research and development involving dose and schedule optimization of radiation and drugs, using representative in vitro and in vivo cancer models to obtain high-quality data to proceed to clinical studies.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081411","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":"Mitigating the Effects of 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol on Gastrointestinal Acute Radiation Syndrome after Total-Body Irradiation in Mice.","authors":"Jinseon Jeong, Sojung Sun, Yong-Jae Kim, Jae Sam Lee, Jae Wha Kim","doi":"10.1667/RADE-24-00126.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00126.1","url":null,"abstract":"<p><p>Total-body irradiation (TBI) with gamma rays can damage organisms in various unexpected ways and trigger several organ dysfunction syndromes, such as acute radiation syndrome (ARS). Hematopoietic cells and enterocytes are particularly sensitive to radiation due to their self-renewal ability and rapid division, which leads to hematopoietic ARS (H-ARS) and gastrointestinal ARS (GI-ARS). We previously showed that a lipid-based small molecule, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), improved 30-day survival and alleviated H-ARS symptoms in BALB/c mice after a lethal dose (LD70/30) of gamma-ray TBI. In this study, we investigated the mitigating effects of PLAG on radiation-induced GI damage that occurs under the same conditions as H-ARS in BALB/c mice. Our study showed that PLAG facilitated the structural restoration of intestinal tissues by increasing villus height, crypt depth, crypt number, mucin-producing goblet cells, and proliferating cell nuclear antigen (PCNA)-positive crypt cells. PLAG significantly improved intestinal absorptive capacity and reduced intestinal injury-induced bacterial translocation. In addition, PLAG effectively inhibited radiation-induced necroptosis signaling activation in the intestinal crypt cells, which was responsible for sustained tissue damage and the release of high mobility group box 1 (HMGB1), a typical damage-associated molecular pattern. Overall, our findings support the radiation-mitigating potential of PLAG against GI-ARS after accidental radiation exposure.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073749","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":"Influence of Age on Leukemia Mortality Associated with Exposure to γ rays and 2-MeV Fast Neutrons in Male C3H Mice.","authors":"Kentaro Ariyoshi, Tatsuhiko Imaoka, Yasushi Ohmachi, Yuka Ishida, Masahiro Uda, Mayumi Nishimura, Mayumi Shinagawa, Midori Yoshida, Toshiaki Ogiu, Mutsumi Kaminishi, Takamitsu Morioka, Shizuko Kakinuma, Yoshiya Shimada","doi":"10.1667/RADE-23-00069.1","DOIUrl":"https://doi.org/10.1667/RADE-23-00069.1","url":null,"abstract":"<p><p>The relative biological effectiveness (RBE) of densely ionizing radiation can depend on the biological context. From a radiological perspective, age is an important factor affecting health risks of radiation exposure, but little is known about the modifying impact of age on the effects of densely ionizing radiation. Herein, we addressed the influence of age on leukemogenesis induced by accelerator-generated fast neutrons (mean energy, ∼2 MeV). Male C3H/HeNrs mice were exposed to 137Cs γ rays (0.2-3.0 Gy) or neutrons (0.0485-0.97 Gy, γ ray contamination 0.0105-0.21 Gy) at 1, 3, 8, or 35 weeks of age and observed over their lifetimes under specific pathogen-free conditions. Leukemia and lymphoma were diagnosed pathologically. Hazard ratio (HR) and RBE for myeloid leukemia mortality as well as the age dependence of these two parameters were modeled and analyzed using Cox regression. Neutron exposure increased HR concordant with a linear dose response. The increase of HR per dose depended on age at exposure, with no significant dose dependence at age 1 or 3 weeks but a significant increase in HR of 5.5 per Gy (γ rays) and 16 per Gy (neutrons) at 8 weeks and 5.8 per Gy (γ rays) and 9 per Gy (neutrons) at 35 weeks. The RBE of neutrons was 2.1 (95% confidence interval, 1.1-3.7), with no dependence on age. The development of lymphoid neoplasms was not related to radiation exposure. The observed increasing trend of radiation-associated mortality of myeloid leukemia with age at exposure supports previous epidemiological and experimental findings. The results also suggest that exposure at the susceptible age of 8 or 35 weeks does not significantly influence the RBE value for neutrons for induction of leukemia, unlike what has been documented for breast and brain tumors.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073748","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":"Radiosensitivity-related Variation in MicroRNA-34a-5p Levels and Subsequent Neuronal Loss in the Hilus of the Dentate Gyrus after Irradiation at Postnatal Days 10 and 21 in Mice.","authors":"Lian Liu, Hong Wang, Zhao Wu Ma, Feng Ru Tang","doi":"10.1667/RADE-23-00248.1","DOIUrl":"https://doi.org/10.1667/RADE-23-00248.1","url":null,"abstract":"<p><p>The radiosensitivity of mice differs between postnatal days 10 (P10) and 21(P21); these days mark different stages of brain development. In the present study, Ki67 and doublecotin (DCX) immunostaining and hematoxylin staining was performed, which showed that acute radiation exposure at postnatal day 10 induced higher cell apoptosis and loss in the hilus of the dentate gyrus at day 1 postirradiation than postnatal day 21. MicroRNA (miRNA) sequencing and real-time quantitative reverse transcription PCR (qRT-PCR) analysis indicated the upregulation of miRNA-34a-5p at days 1 and 7 days after irradiation at postnatal day 10, but not at postnatal day 21. Down-regulation of T-cell intracytoplasmic antigen-1 pathway (Tia1) was indicated by qRT-PCR at day 1 day but not day 7 after irradiation at postnatal day 10. Neurobehavioral testing in mature mice irradiated at postnatal day 10 demonstrated the impairment of short-term memory in novel object recognition and spatial memory, compared to those irradiated at postnatal day 21. Combined with our previous luciferase assay showing the direct interaction of miRNA34a-5p and Tia1, these findings suggest that radiation-induced abnormal miR-34a-5p/Tial interaction at day 1 after irradiation at postnatal day 10 may be involved in apoptosis of the dentate gyrus hilar, impairment of neurogenesis and subsequent short-term memory loss as observed in the novel object recognition and Barnes maze tests.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009329","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":"Risks of Circulatory Diseases among Korean Radiation Workers Exposed to Low-dose Radiation.","authors":"Eun Shil Cha, Dalnim Lee, Hyoju Sung, Won Il Jang, Tae-Eun Kwon, Ho Yeon Jeong, Songwon Seo","doi":"10.1667/RADE-23-00148.1","DOIUrl":"https://doi.org/10.1667/RADE-23-00148.1","url":null,"abstract":"<p><p>High-dose radiation has been widely recognized as a risk factor for circulatory diseases. There is increasing evidence for risk of circulatory diseases in response to low and moderate radiation doses in recent years, but the results are not always consistent. We aimed to evaluate the associations between low-dose radiation exposure (<0.1 Gy) and the incidence of circulatory disease in a large cohort of Korean radiation workers. We collected data from a cohort of 187,001 radiation workers monitored for personal radiation dose since 1984 and linked with the National Health Insurance Service data from 2002 to 2021. Excess relative risks (ERRs) per 100 mGy were calculated to quantify the radiation dose-response relationship. The mean duration of follow-up was 13.3 years. A total of 12,705 cases of cerebrovascular disease (CeVD) and 19,647 cases of ischemic heart disease (IHD) were diagnosed during the follow-up period (2002-2021). The average cumulative heart dose was 4.10 mGy, ranging from 0 to 992.62 mGy. The ERR per 100 mGy with 10-year lagged cumulative heart doses was estimated at -0.094 (95% CI -0.248, 0.070) for CeVD and -0.173 (95% CI -0.299, -0.041) for IHD. The ERRs were not significantly changed after adjusting for confounding factors such as smoking, income, blood pressure, body mass index, and blood glucose level. A linear quadratic model was found to provide a better fit for the ERR of CeVD and IHD than a linear model (P = 0.009 and 0.030, respectively). There were no statistically significant variations in ERR/100 mGy estimates for either CeVD or IHD in terms of sex, attained age, and duration of employment; however, heterogeneity in the ERR/100 mGy estimates for CeVD among occupations was observed (P = 0.001). Our study did not find conclusive evidence supporting the association between occupational low-dose radiation and an increased risk of circulatory diseases. The significant negative ERR estimates for IHD need further investigation with a more extended follow-up period.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988712","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":"Dose Reconstruction for Epidemiological Studies among Ukrainian Chernobyl Cleanup Workers.","authors":"Vladimir Drozdovitch, Victor Kryuchkov, Elena Bakhanova, Petro Bondarenko, Konstantin Chizhov, Ivan Golovanov, Vadim Chumak","doi":"10.1667/RADE-23-00117.1","DOIUrl":"https://doi.org/10.1667/RADE-23-00117.1","url":null,"abstract":"<p><p>The present paper provides an overview of the methods and summarizes the results of estimating radiation doses and their uncertainties for Ukrainian-American epidemiological studies among the Chernobyl (Chornobyl) cleanup workers. After the Chernobyl accident occurred on April 26, 1986, more than 300,000 Ukrainian cleanup workers took part between 1986 and 1990 in decontamination and recovery activities at the site of the Chernobyl Nuclear Power Plant. The U.S. National Cancer Institute in collaboration with the Ukrainian National Research Center for Radiation Medicine conducted several epidemiological studies in this population. An important part of these studies was the reconstruction of the study participants' radiation doses and the assessment of uncertainties in doses. A method called realistic analytical dose reconstruction with uncertainty estimation (RADRUE) was used to calculate the doses from external irradiation during cleanup missions, which was the main exposure pathway for most study participants. At the initial phase of the accident during the atmospheric releases of radioactivity from the destroyed reactor, the cleanup workers also received doses from inhalation of radionuclides. In addition, study participants received doses at their places of residence, especially those who lived in highly contaminated areas. The radiation doses estimated for 2,048 male cleanup workers included in the Ukrainian-American epidemiological studies varied widely: (i) bone-marrow doses from external irradiation in the case-control study of leukemia of 1,000 cleanup workers ranged from 3.7 × 10-5 mGy to 3.3 Gy (mean = 92 mGy); (ii) thyroid doses in the case-control study of thyroid cancer in 607 persons from all exposure pathways combined were from 0.15 mGy to 9.0 Gy (mean = 199 mGy); (iii) gonadal doses in 183 cleanup workers from all exposure pathways combined in the study of germline mutations in the offspring after parental irradiation (trio study) ranged from 0.58 mGy to 4.1 Gy (mean = 392 mGy); (iv) thyroid doses in the human factor uncertainties study among 47 persons were from 20 mGy to 2.1 Gy (mean = 295 mGy); and (v) lung doses in the study of germline genetic variants associated with host susceptibility to COVID-19 estimated for 211 cleanup workers were from 0.024 mGy to 2.5 Gy (mean = 249 mGy). Doses of female cleanup workers were much lower than those of male cleanup workers: the mean doses for female cleanup workers were 27 mGy for 34 women included in the trio study and 56 mGy for 48 women participated in the study of germline genetic variants associated with host susceptibility to COVID-19. Uncertainties in dose estimates included two components: (i) inherent uncertainties arising from the stochastic random variability of the parameters used in exposure assessment and from a lack of knowledge about the true values of the parameters; and (ii) human factor uncertainties due to poor memory recall resulting in incomplete, inaccurate, ","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983121","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":"Rapamycin Reduces Carcinogenesis and Enhances Survival in Mice when Administered after Nonlethal Total-Body Irradiation.","authors":"Anastasia L Sowers, Sangeeta Gohain, Elijah F Edmondson, Rajani Choudhuri, Murali C Krishna, John A Cook, James B Mitchell","doi":"10.1667/RADE-24-00111.1","DOIUrl":"https://doi.org/10.1667/RADE-24-00111.1","url":null,"abstract":"<p><p>The rationale of this study stems from the concern of a radiation-induced accident or terrorist-mediated nuclear attack resulting in large populations of people exposed to nonlethal radiation doses or after a course of definitive radiation therapy which could substantially increase the risk for cancer induction after exposure. Currently, there are no safe and effective interventions to reduce this increased cancer risk to humans. We have tested the hypothesis that the mTOR inhibitor, rapamycin, administered in the diet of mice would reduce or delay radiation-induced cancer when given after radiation exposure. A total-body irradiation (TBI) of 3 Gy was administered to female C3H/Hen mice. Immediately after TBI, along with untreated control groups, animals were placed on chow containing different concentrations of encapsulated rapamycin (14, 40, 140 mg/kg chow). Animals remained on the respective control or rapamycin diets and were followed for their entire lifespan (total of 795 mice). The endpoint for the study was tumor formation (not to exceed 1 cm) or until the animal reached a humane endpoint at which time the animal was euthanized and evaluated for the presence of tumors (pathology evaluated on all animals). Kaplan-Meier survival curves revealed that all three concentrations of rapamycin afforded a significant survival advantage by delaying the time at which tumors appeared and reduction of the incidence of certain tumor types such as hepatocellular carcinomas. The survival advantage was dependent on the rapamycin concentration used. Further, there was a survival advantage when delaying the rapamycin chow by 1 month after TBI. Rapamycin is FDA-approved for human use and could be considered for use in individuals exposed to nonlethal TBI from a nuclear accident or attack or after significant therapeutic doses for cancer treatment.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983123","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}