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Gene expression profiles of irradiated lung tissue in three mouse strains

ABSTRACT: The aim of our research is to clarify the mechanisms generating heterogeneity in response to C-ion irradiation that arise from individual genetic variations in humans. In this study, we performed whole lung C-ion irradiation using three different strains of mice to examine whether strain-dependent differences in radiation effects occur in high-LET C-ion thoracic irradiation. Murine strain-variance was evaluated by histopathological examination of intra-alveolar hemorrhage that is likely to occur during the early phase after irradiation, and of lung fibrosis during the late phase, occurring more than three months after irradiation. We also performed microarray analysis to identify the key genes that are differentially regulated in different mouse strains after C-ion irradiation and to determine the mechanism of strain-dependent pulmonary damage after high-LET C-ion irradiation.

ORGANISM(S): Mus musculus

PROVIDER: GSE20959 | GEO | 2014/02/26

SECONDARY ACCESSION(S): PRJNA124519

REPOSITORIES: GEO

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Gene expression profiles of irradiated lung tissue in three mouse strains

Project description:The aim of our research is to clarify the mechanisms generating heterogeneity in response to C-ion irradiation that arise from individual genetic variations in humans. In this study, we performed whole lung C-ion irradiation using three different strains of mice to examine whether strain-dependent differences in radiation effects occur in high-LET C-ion thoracic irradiation. Murine strain-variance was evaluated by histopathological examination of intra-alveolar hemorrhage that is likely to occur during the early phase after irradiation, and of lung fibrosis during the late phase, occurring more than three months after irradiation. We also performed microarray analysis to identify the key genes that are differentially regulated in different mouse strains after C-ion irradiation and to determine the mechanism of strain-dependent pulmonary damage after high-LET C-ion irradiation. Eight-week old female inbred C3H/He Slc, C57BL/6J Jms Slc and A/J Jms Slc mice (3 kinds of mice) were used. The whole thorax of three mice was locally irradiated at 10 Gy with C-ion beams, with a reference beam, 137Cs gamma-rays (2 kinds of beam). Three mice of each strain (3 mice) were sacrificed, and immediately dissected for lung extraction at 6 h (6h sample). Lungs for three mice of each strain without irradiation were extracted at the same time as control samples (control sample). Hybridization to microarrays (Whole Mouse Genome 4x44K OligoMicroarray Kit, single color, Cyamine 3-CTP) consisting of 44,000 total spots was conducted using an Agilent Gene Expression hybridization kit. The arrays from three independent replicates for each sample (3 arrays) were scanned on an Agilent dual-laser Microarray Scanner (all from Agilent Technologies) following the manufacturer's instructions. A total of 108 samples were analyzed. 3 replicate arrays x 3 mice x 3 strains x 2 timing for sampling x 2 kinds of beam.

2014-02-26 | E-GEOD-20959 | biostudies-arrayexpress

Effects of irradiation on mouse lung

Project description:Total lung RNA from 3 mouse strains after 18Gy thoracic irradiation. Thoracic cavity radiotherapy is limited by the development of alveolitis and fibrosis in susceptible patients. To define the response to 18 Gy pulmonary irradiation in mice, at the expression level, and to identify pathways which may influence the alveolitis and fibrosis phenotypes expression profiling was completed. Male mice of three strains, A/J (late alveolitis response), C3H/HeJ (C3H, early alveolitis response) and C57BL/6J (B6, fibrosis response) were exposed to thoracic radiation, euthanised when moribund and lung tissue gene expression was assessed with microarrays. treated vs. control in 3 strains

2009-09-11 | E-GEOD-2250 | biostudies-arrayexpress

Effects of irradiation on mouse lung

2009-09-11 | GSE2250 | GEO

RNA sequencing analysis of lung samples of control and irradiated animals

Project description:Purpose: Radiation-induced lung injury (RILI) is a progressive condition, with an early phase, radiation pneumonitis (RP), and a late phase, lung fibrosis (LF). RILI may occur after partial body ionizing radiation exposures or by internal radioisotope exposure, with wide individual variability in timing and extent of lung injury. This study aims to provide new insights into the pathogenesis and progression of RILI in the non-human primate (NHP) rhesus macaque model. Methods:We used an integrative approach to understand RILI and its evolution at clinical and molecular levels in seventeen NHPs exposed to10 Gy of whole thorax irradiation in comparison to three sham-irradiated control NHPs. Lung samples were collected at necropsy for molecular and histopathological analyses using RNA sequencing and immunohistochemistry Results: Our data enhances understanding of RILI in non-survivors and survivors in a NHP model. RNA sequencing highlighted the role of SERPINA3, ATP12A, GJB2, CLDN10, TOX3, LPA as possible biomarkers and potential therapeutic targets of RILI. Their differential expression in nonsurvivors and survivors correlated with the severity of the disease.

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Gene expression profiles of primary tumors with radiotherapy and lung metastases in mouse squamous cell carcinoma model.

2009-04-23 | GSE9305 | GEO

Microarray analysis of rice plants irradiated with carbon ion beams (HIMAC)

Project description:In this study, carbon-ion beams generated via the heavy-ion medical accelerator in Chiba (HIMAC) were targeted to growing rice seedlings (7-days-old) to examine their effect on this genome model. Both physiological parameters, such as growth, and molecular events, specially the gene expression profiles were examined immediately after irradiation (at 270 Gy dose) by rice oligo (22K) DNA microarrays. Genome-wide transcriptional profiling of radiation-response genes in rice provides us with first report on how our radioactive environment affects a plant species. Keywords: Irradiation response

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Transcriptome of Irradiated Microglia

Project description:Whole brain irradiation remains important in the management of brain tumors. Although necessary for improving survival outcomes, cranial irradiation also results in cognitive decline in long-term survivors. A chronic inflammatory state characterized by microglial activation has been implicated in radiation-induced brain injury, and here we present a comprehensive transcriptional profile of irradiated microglia. Fluorescence-activated cell sorting (FACS) was used to isolate CD11b+ microglia from the hippocampi of C57BL/6 and Balb/c mice 1 month after 10Gy cranial irradiation. Affymetrix gene expression profiles were evaluated using linear modeling and rank product analyses. A conserved signature of irradiation was identified across strains, and gene set enrichment analysis was employed to functionally compare our signature to publically available mouse and human datasets.

2014-12-31 | GSE55968 | GEO

Gene expression data from the sham and irradiated lungs of three murine strains with well-characterized phenotypic variation in pulmonary radiation response.

Project description:Intrinsic variations in the development of lung injury among patients undergoing radiotherapy for tumors in the thoracic region suggest there are one or more genes that influence the development and severity of radiation pneumonitis and/or fibrosis. We hypothesized well-characterized murine strain differences in pulmonary response to radiation may offer a novel method to extract the specific genes and/or pathways participating in the development of pneumonitis and/or fibrosis.

2017-02-08 | GSE85359 | GEO

Gene expression profiles of primary tumors with radiotherapy and lung metastases in mouse squamous cell carcinoma model.

Project description:To examine whether the local carbon ion radiotherapy affects the characteristics of the metastatic tumors, the expression profiles of the primary tumors and the lung metastases were studied in a mouse squamous cell carcinoma model by applying local radiotherapy with no irradiation (negative control), gamma-ray irradiation (reference beam), and carbon-ion irradiation. Keywords: mouse, squamous cell carcinoma, primary tumor, lung metastases, radiotherapy, carbon ion, gamma ray A highly metastatic mouse squamous cell carcinoma NR-S1 was implanted into the hind leg of synergetic C3H/HeNrs mice and irradiated with 5 Gy of carbon ion beam. 8 Gy of gamma ray was used as a reference beam. At 2 weeks after the irradiation, the lung tissue was sampled. In order to collect samples of primary tumors, the tumors were implanted in other mice and irradiated in the same manner, and the primary tumors were collected at 1 week after the irradiation. The tumor cells of the primary and metastatic tumors were collected by laser microdissection, and oligonucleotide microarray analysis of the irradiated primary tumors and the metastatic tumors were all performed in comparison to the non-irradiated primary tumor by two-color methods.

2009-04-22 | E-GEOD-9305 | biostudies-arrayexpress

Single cell RNAseq analysis of mouse lung after irradiation

Project description:Thoracic radiation therapy is limited by the development of acute (i.e. pneumonitis) and late (i.e. pulmonary fibrosis) side-effects. The goal of this study is to analyze, at the single cell level, the molecular impact of two radiation treatments : a conventional/clinical (CONV) modality vs. FLASH, a new radiation method that spares healthy tissue from late radiation-induced toxicities (Science Translational Medicine 6: 245ra293, 2014). We analyzed by single cell RNA sequencing (scRNAseq) dissociated lung cells from a non-irradiated control mouse (NI), a mouse 4 days after CONV thoracic irradiation (CONV) and a mouse 4 days after FLASH irradiation (FLASH). We identify transcriptional alterations induced in the distinct lung cell types after irradiation and show that FLASH irradiated lung cells present a reduced pro-inflammatory phenotype as well as a diminished activation of epithelial lung progenitor cells. In line with previous report (Radiother Oncol 124: 365-9, 2017), this study indicates that FLASH radiation therapy limits inflammation and preserves the regenerative capcity of the lung.

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