Project description:Exposure to high-doses of ionizing radiation (IR) leads to development of a strong acute radiation syndrome (ARS) in mammals. ARS manifests after a latency period and it is important to develop fast prognostic biomarkers for its early detection and assessment. Analysis of chromosomal aberrations in peripheral blood lymphocytes is the gold standard of biological dosimetry, but it fails after high doses of IR. Therefore, it is important to establish novel biomarkers of exposure that are fast and reliable also in the high dose range. Here, we investigated the applicability of miRNA levels in mouse serum.
Project description:<p>Long-term low-dose ionizing radiation (LLIR) widely exists in human life and has been confirmed to have potential pathogenic effects on cancer and cardiovascular diseases. However, it is technically and ethically unfeasible to explore LLIR-induced phenotypic changes in the human cohort, leading to slow progress in revealing the pathogenesis of LLIR. In this work, we recruited 32 radiation workers and 18 healthy non-radiation workers from the same city with the same eating habits for radiation damage evaluation and metabolomics profiling. It was found that clear metabolic phenotypic differences existed between LLIR and non-LLIR exposed participants. Moreover, LLIR exposed workers can be further divided into 2 types of metabolic phenotypes, corresponding to high and low damage types, respectively. 3-hydroxypropanoate and glycolaldehyde were identified as sensitive indicators to radiation damage, which specific response to the chromosomal aberration of workers and may be potential monitoring markers for LLIR protection. Taurine metabolism-related pathways were identified as the main differential metabolic pathway under LLIR inducing, which had been confirmed to have a response to acute or chronic radiation exposure. We expect our study can be helpful to LLIR damage monitoring and symptomatic intervention in the future.</p>
Project description:Exposure to high-dose radiation causes life-threatening serious intestinal damage. Histological analysis is the most accurate method for judging the extent of intestinal damage after death. However, it is difficult to predict the extent of intestinal damage to body samples. Here we focused on extracellular microRNAs (miRNAs) released from cells and investigated miRNA species that increased or decreased in serum and feces using a radiation-induced intestinal injury mouse model. A peak of small RNA of 25–200 nucleotides was detected in mouse serum and feces 72 h after radiation exposure, and miRNA presence in serum and feces was inferred. MiRNAs expressed in the small intestine and were increased by more than 2.0-fold in serum or feces following a 10 Gy radiation exposure were detected by microarray analysis and were 4 in serum and 19 in feces. In this study, miR-375-3p, detected in serum and feces, was identified as the strongest candidate for a high-dose radiation biomarker in serum and/or feces using a radiation-induced intestinal injury model.
Project description:Male mice 10-14 weeks of age were exposed in vivo to 10 rad X-ray. The objective is to extract information on gene networks from the microarray data. Keywords: Ionizing radiation
Project description:Skin is usually exposed during human exposures to ionizing radiation, however there are few experiments that evaluate the radiation responsiveness of the cells of the epidermis (keratinocytes) and those of the dermis (fibroblasts) in the same studies. We evaluated the transcriptional responses of quiesent primary keratinocytes and fibroblasts from the same individual and compared them with quiescent keratinocytes and fibroblasts that were immortalized by human telomerase (hTert). The primary transcriptional responses to 10-500 cGy ionizing radiation were p53-mediated responses; however, we did identify distinct responses between the keratinocytes and the fibroblasts. Keywords: keratinocytes and fibroblasts - dose response to ionizing radiation
Project description:Characterization of biological and chemical responses to ionizing radiation by various organisms is essential for potential applications in bioremediation, alternative modes of detecting nuclear material, and national security. Escherichia coli DH10β is an optimal system to study the microbial response to low-dose ionizing radiation at the transcriptional level because it is a well-characterized model bacterium and its responses to other environmental stressors, including those to higher radiation doses, have been elucidated in prior studies. In this study, RNA sequencing with downstream transcriptomic analysis (RNA-seq) was employed to characterize the global transcriptional response of stationary-phase E. coli subjected to Pu-239, H-3 (tritium), and Fe-55, at an approximate absorbed dose rate of 10 mGy day-1 for 1 day and 15 days. Differential expression analysis identified significant changes in gene expression of E. coli for both short- and long-term exposures. Radionuclide source exposure induced differential expression in E. coli of genes involved in biosynthesis pathways of nuclear envelope components, amino acids, and siderophores, transport systems such as ABC transporters and type II secretion proteins, and initiation of stress response and regulatory systems of temperature stress, the RpoS regulon, and oxidative stress. These findings provide a basic understanding of the relationship between low-dose exposure and biological effect of a model bacterium that is critical for applications in alternative nuclear material detection and bioremediation. IMPORTANCE Escherichia coli strain DH10β, a well-characterized model bacterium, was subjected to short-term (1-day) and long-term (15-day) exposures to three different in situ radiation sources comprised of radionuclides relevant to nuclear activities to induce a measurable and identifiable genetic response. We found E. coli had both common and unique responses to the three exposures studied, suggesting both dose rate- and radionuclide-specific effects. This study is the first to provide insights into the transcriptional response of a microorganism in short- and long-term exposure to continuous low-dose ionizing radiation with multiple in situ radionuclide sources and the first to examine microbial transcriptional response in stationary phase. Moreover, this work provides a basis for the development of biosensors and informing more robust dose-response relationships to support ecological risk assessment.
Project description:Dose dependent expression of extracellular microRNAs in HCT116 colorectal cancer cells exposed to high dose rate ionizing radiation
Project description:Gene expression profiles of peripheral blood samples from C57BL/6 mice exposed with ionizing radiation. We used mice as model animal to study biologial recovery response after radiation damage. Therefore, we obtained gene expression profiles from C57BL/6 mice exposed with various levels of ionizing radiation, including low and high doses and control groups. In order to measure recovery rate, we collected peripheral blood samples at different time durations after the exposure. In order to obtain robust signatures specific to radiation response, we are interested in knowing if the radiation signarures will be present in the presence of confounders. Therefore, mice were given intraperitoneal injections of lipopolysaccharide endotoxin (LPS), or treated with granulocyte colony-stimulating factor (GCSF), otherwise no treatment after ionizing radiation exposure. The underlying mechanism of confounder treatment is that LPS induces strong immune response resembling the effect of infection, and GCSF stimulates mobilization of HSCs. Exploratory analysis shows that the confounding effects did affect the radiation signature to some extent. This study provides insights into the molecular basis of time- and dose- dependent response to ionizing radiation in mice hematopoietic system.