Radiation research最新文献

This study offers a review of published data on DNA double strand break (DSB) repair kinetics after exposure to ionizing radiation. By compiling a database, which currently includes 285 DNA DSB repair experiments utilizing both photons and ions, we investigate the impact of distinct experimental parameters on the kinetics of DNA DSB repair. Methodological differences and inconsistencies in reporting make the comparison of data generated by different research groups challenging. Nevertheless, by implementing filtering criteria, we can compare repair kinetics obtained with normal and tumor cells derived from human or animal tissues, as well as cells exposed to photons or ions ranging from hydrogen to iron ions. In addition, several repair curves of repair deficient cell lines were included. The study aims to provide researchers with a comprehensive overview of experimental factors that may confound results and emphasize the importance of precise reporting of experimental parameters. Moreover, we identify gaps in the literature that require attention in future studies, aiming to address clinically relevant questions related to radiotherapy. The database can be freely accessed at: https://github.com/weradstake/DRDNA.

Micronuclei, detected through the cytokinesis-block micronucleus assay, are valuable indicators of ionizing radiation exposure, especially in short-term lymphocyte cultures. The peripheral human blood lymphocyte assay is recognized as a prime candidate for automated biodosimetry. In a prior project at the Columbia University Center for Radiological Research, we automated this assay using the 96-well ANSI/SLAS microplate standard format and relied on established biotech robotic systems named Rapid Automated Biodosimetry Tool (RABiT). In this study, we present the application of a similar automated biotech setup at an external high-throughput facility (RABiT-III) to implement the same automated cytokinesis-block micronucleus assay. Specifically, we employed the Agilent BRAVO liquid-handling system and GE IN Cell Analyzer 6000 imaging system in conjunction with the PerkinElmer Columbus image data storage and analysis system. Notably, this analysis system features an embedded PhenoLOGIC machine learning module, simplifying the creation of cell classification algorithms for CBMN assay image analysis and enabling the generation of radiation dose-response curves. This investigation underscores the adaptability of the RABiT-II CBMN protocol to diverse RABiT-III biotech robotic platforms in non-specialized biodosimetry centers. Furthermore, it highlights the advantages of machine learning in rapidly developing algorithms crucial for the high-throughput automated analysis of RABiT-III images.

Radiation enteritis is a common complication of abdominal and pelvic radiotherapy. Several previous studies showed that fecal microbiota transplantation (FMT) could alleviate radiation enteritis. In this study, we investigated the efficacy of FMT in alleviating radiation enteritis and explored the mechanisms by multi-omics approaches. Briefly, C57BL/6J mice were subjected to 9 Gy irradiation to the localized abdominal field, and randomized received FMT from healthy donor mice or saline. H&E staining of harvested small intestine showed FMT decreased epithelial injury. Radiation-induced microbiota dysbiosis, characterized by a decrease in beneficial bacteria Lactobacillaceae and Lachnospiraceae, while these bacteria were restored by FMT. Fecal metabolomics analysis revealed that FMT modulated metabolic dysregulation. Two tryptophan pathway metabolites, indole-3-acetaldehyde and N-Acetyl-5-hydroxytryptamine were decreased after irradiation, whereas these metabolites showed a pronounced recovery in mice receiving FMT. Proteomics analysis of small intestine indicated that radiation enteritis triggered immune-inflammatory responses, which were potentially mitigated by FMT. In 21 patients receiving pelvic radiotherapy for cervical cancer, those who developed enteritis (n = 15) had higher abundance in Lachnospiraceae. Moreover, Indole-3-acetaldehyde was reduced after irradiation. These findings provide insights into the therapeutic effects of FMT in radiation enteritis and highlight Lachnospiraceae and the tryptophan metabolite, Indole-3-acetaldehyde may protect against radiation enteritis.

The linear, non-threshold (LNT) hypothesis of cancer induction derived from studies of populations exposed to moderate-to-high acute radiation doses may not be indicative of cancer risks associated with lifetime radiation exposures less than 100 mSv. The objective of this study was to examine risks and dose-response patterns of lymphohematopoietic cancer (LHC) and its types associated with low radiation exposure while adjusting for possible confounding factors. A retrospective cohort of 437,937 U.S. nuclear shipyard workers (153,930 radiation and 284,007 non-radiation workers) was followed from 1957 to 2011, with 3,699 LHC deaths observed. The risk of LHC in radiation workers was initially compared to the risk in non-radiation workers. Time dependent accumulated radiation dose, lagged 2 years, was used in categorical and continuous dose analysis among radiation workers to examine the LHC risks and possible dose-response relationships based on Poisson regression models. These analyses controlled for sex, race, time dependent age, calendar time, socioeconomic status, solvent-related last job, and age at first hire. The median lifetime radiation dose for the radiation worker population was 0.82 mSv and the 95th percentile dose was 83.63 mSv. The study shows: 1. LHC mortality for radiation workers was significantly lower than non-radiation workers relative risk: 0.927; 95% confidence intervals (95% CI): 0.865, 0.992; P = 0.030]. Among LHC types, the risks for lymphoid leukemia and lymphomas in radiation workers were lower than the risk in non-radiation workers with statistical significance, while the risk for the rest of LHC types did not show any statistically significant difference. 2. In categorical dose analysis among radiation workers, sample size weighted linear trend of relative risk (RRs) for LHC and its types in five dose categories (>0-<25, 25-<50, 50-<100, 100-<200, and > = 200 mSv) vs. 0 mSv were not statistically significant, although there was an elevation of RR for chronic myeloid leukemia only in the 50-<100 mSv category (RR: 2.746; 95% CI: 1.002, 7.521; P = 0.049) vs. 0 mSv. 3. The Poisson regression analyses among radiation workers using the time dependent radiation dose as a continuous variable showed an excess relative risk (ERR) for LHC at 100 mSv of 0.094 (95% CI: -0.037, 0.225; P = 0.158) and leukemia less chronic lymphoid leukemia, of 0.178 (95% CI: -0.085, 0.440; P = 0.440) vs. 0 mSv. The ERRs and their linear trend for all other types were not statistically significant.

The current geopolitical context has brought the radiological nuclear risk to the forefront of concerns. High-dose localized radiation exposure leads to the development of a musculocutaneous radiation syndrome affecting the skin and subcutaneous muscles. Despite the implementation of a gold standard treatment based on an invasive surgical procedure coupled with autologous cell therapy, a muscular defect frequently persists. Targeting the modulation of the Hedgehog (Hh) signaling pathway appears to be a promising therapeutic approach. Activation of this pathway enhances cell survival and promotes proliferation after irradiation, while inhibition by Cyclopamine facilitates differentiation. In this study, we compared the effects of three antagonists of Hh, Cyclopamine (CA), Vismodegib (VDG) and Sonidegib (SDG) on differentiation. A stable cell line of murine myoblasts, C2C12, was exposed to X-ray radiation (5 Gy) and treated with CA, VDG or SDG. Analysis of proliferation, survival (apoptosis), morphology, myogenesis genes expression and proteins production were performed. According to the results, VDG does not have a significant impact on C2C12 cells. SDG increases the expression/production of differentiation markers to a similar extent as CA, while morphologically, SDG proves to be more effective than CA. To conclude, SDG can be used in the same way as CA but already has a marketing authorization with an indication against basal cell cancers, facilitating their use in vivo. This proof of concept demonstrates that SDG represents a promising alternative to CA to promotes differentiation of murine myoblasts. Future studies on isolated and cultured satellite cells and in vivo will test this proof of concept.

A complex cascade of systemic and tissue-specific responses induced by exposure to ionizing radiation can lead to functional impairment over time in the surviving population. Current methods for management of survivors of unintentional radiation exposure episodes rely on monitoring individuals over time for the development of adverse clinical symptoms due to the lack of predictive biomarkers for tissue injury. In this study, we report on changes in metabolomic and lipidomic profiles in multiple tissues of nonhuman primates (NHPs) that received either 4.0 Gy or 5.8 Gy total-body irradiation (TBI) of 60Co gamma rays, and 4.0 or 5.8 Gy partial-body irradiation (PBI) from LINAC-derived photons and were treated with a promising radiation countermeasure, gamma-tocotrienol (GT3). These include small molecule alterations that correlate with radiation effects in the jejunum, lung, kidney, and spleen of animals that either survived or succumbed to radiation toxicities over a 30-day period. Radiation-induced metabolic changes in tissues were observed in animals exposed to both doses and types of radiation, but were partially alleviated in GT3-treated and irradiated animals, with lung and spleen being most responsive. The majority of the pathways protected by GT3 treatment in these tissues were related to glucose metabolism, inflammation, and aldarate metabolism, suggesting GT3 may exert radioprotective effects in part by sparing these pathways from radiation-induced dysregulation. Taken together, the results of our study demonstrate that the prophylactic administration of GT3 results in metabolic and lipidomic shifts that likely provide an overall advantage against radiation injury. This investigation is among the first to highlight the use of a molecular phenotyping approach in a highly translatable NHP model of partial- and total-body irradiation to determine the underlying physiological mechanisms involved in the radioprotective efficacy of GT3.

The development of effective uses of biodosimetry in large-scale events has been hampered by residual, i.e., "legacy" thinking based on strategies that scale up from biodosimetry in small accidents. Consequently, there remain vestiges of unrealistic assumptions about the likely magnitude of victims in "large" radiation events and incomplete analyses of the logistics for making biodosimetry measurements/assessments in the field for primary triage. Elements remain from an unrealistic focus on developing methods to use biodosimetry in the initial stage of triage for a million or more victims. Based on recent events and concomitant increased awareness of the potential for large-scale events as well as increased sophistication in planning and experience in the development of biodosimetry, a more realistic assessment of the most effective roles of biodosimetry in large-scale events is urgently needed. We argue this leads to a conclusion that the most effective utilization of biodosimetry in very large events would occur in a second stage of triage, after initially winnowing the population by identifying those most in need of acute medical attention, based on calculations of geographic sites where significant exposures could have occurred. Understanding the potential roles and limitations of biodosimetry in large-scale events involving significant radiation exposure should lead to development of the most effective and useful biodosimetric techniques for each stage of triage for acute radiation syndrome injuries, i.e., based on more realistic assumptions about the underlying event and the logistics for carrying out biodosimetry for large populations.