Microarray analysis of lymphocytes isolated from healthy donors ex-vivo exposed to alpha particle radiation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE80547 | GEO | 2016/04/22
SECONDARY ACCESSION(S): PRJNA319249
REPOSITORIES: GEO
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Project description:Four human-derived cell types: transformed monocytes (THP-1), transformed lung epithelial cells (A549), normal human pulmonary endothelial cells (HPEAC) and normal lung fibroblasts (HFL-1) Cell types were independently exposed to alpha particle radiation using Americium-241 discs (0.9Gy/hr) at a dose range from 0-1.5 Gy. Twenty-four hours post-exposure cells were harvested and RNA was extracted and subjected to microarray analysis.
2016-05-04 | GSE81067 | GEO
Project description:The bystander effect from ionizing radiation consists of cellular responses generated from unirradiated cells to the irradiation of their neighbors. The bystander effect can lead to DNA damage and genomic instability in the affected cells. This non-targeted effect of radiation has received attention due to its potential implications for cancer therapy and radiation protection. Although studied extensively, a complete understanding of its molecular mechanism is the subject of ongoing research. While many studies have targeted specific factors which are suggested to be involved in the bystander effect, few have looked at whole genome gene expression in bystander cells. Furthermore, even fewer studies have looked at the expression in noncancerous human cell lines. In this study we have used a genome-wide microarray approach to investigate transcriptional responses in irradiated and bystander immortalized human fibroblasts following 0.1 Gy α-particle irradiation.
2011-09-14 | GSE32091 | GEO
Project description:The bystander effect from ionizing radiation consists of cellular responses generated from unirradiated cells to the irradiation of their neighbors. The bystander effect can lead to DNA damage and genomic instability in the affected cells. This non-targeted effect of radiation has received attention due to its potential implications for cancer therapy and radiation protection. Although studied extensively, a complete understanding of its molecular mechanism is the subject of ongoing research. While many studies have targeted specific factors which are suggested to be involved in the bystander effect, few have looked at whole genome gene expression in bystander cells. Furthermore, even fewer studies have looked at the expression in noncancerous human cell lines. In this study we have used a genome-wide microarray approach to investigate transcriptional responses in irradiated and bystander immortalized human fibroblasts following 0.1 Gy ?-particle irradiation. Total RNA was isolated from F11hTERT fibroblasts irradiated with 0.1 Gy ?-particles and bystander fibroblasts receiving medium from control (sham irradiated) and irradiated cells (0.1 Gy). RNA was isolated 4, 8 and 26 h after irradiation.
2011-09-13 | E-GEOD-32091 | biostudies-arrayexpress
Project description:Space particle radiation is a major environmental factor in spaceflight, and it is known to cause body damage and even trigger cancer, but with unknown molecular etiologies. To examine these causes, we developed a systems biology analytical approach that included co-expression network analysis of transcriptomics profiles obtained using different α-particle radiation exposures of BEAS-2B human bronchial epithelial cells. These exposures employed either single high-dose irradiation of 0.5 Gy one time, or, multiple low-dose irradiations consisting of 25 exposures to 0.02 Gy once every three days. These exposures were then followed by differential network comparative analysis through the multiscale interactomes. Overall pathway analysis based on the global network and the core modules showed that genes in the multiple low-dose irradiation groups had higher significant enrichment for the extracellular matrix (ECM)-receptor interaction pathway. Then, collagen gene COL1A1 was screened as an important ECM-related gene in the multiple low-dose irradiation group assessed by network robustness parameters, and an expression study of lung adenocarcinoma samples from The Cancer Genome Atlas (TCGA) database and additional biological experiments was performed. COL1A1 was found to promote the emergence of the neoplastic characteristics of BEAS-2B cells by both in vitro experimental analyses and in vivo immunohistochemical staining. These findings suggested that the degree of malignant transformation of cells exposed to multiple low-dose irradiations was greater than that of a single high-dose irradiation, which may be caused by the dysregulation of the ECM-receptor pathway. This study provides information on the molecular mechanisms underlying multiple low-dose irradiations used to mimic spaceflight, with a combination of high-throughput RNA-seq-based transcriptomics and systems biology approaches.
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Project description:IMR90 bystander experiment 0.5 Gy alpha particle
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Project description:Alpha-particle emitters have recently been explored as valuable therapeutic radionuclides. Yet, toxicity to healthy organs and cancer radioresistance limit the efficacy of targeted alpha-particle therapy (TAT). Identification of the radiation-activated mechanisms, which drive cancer cell survival, provides opportunities to develop new points for therapeutic interference to improve the efficacy and safety of TAT. Quantitative phosphoproteomics and matching proteomics followed were employed to identify alterations in the signaling networks in response to TAT with actinium-225 labeled minigastrin analogue 225Ac-PP-F11N in A431 cells, which overexpress cholecystokinin B receptor (CCKBR).
2023-06-02 | PXD039033 | Pride
Project description:Exposure to low dose irradiation causes transiently elevated expression of a long ncRNA PARTICLE (Gene PARTICL- 'Promoter of MAT2A-Antisense RadiaTion Induced Circulating LncRNA). PARTICLE affords both a cytosolic scaffold for the tumor suppressor methionine adenosyltransferase (MAT2A) and a nuclear genetic platform for transcriptional repression. In situ hybridisation discloses that PARTICLE-MAT2A associate together following irradiation. Bromouridine tracing and presence in exosomes indicate intercellular transport, and this is supported by ex-vivo data from radiotherapy-treated patients. Surface plasmon resonance indicates that PARTICLE forms a DNA-lncRNA triplex upstream of a MAT2A promoter CpG island. We show that PARTICLE represses MAT2A via methylation and demonstrate that the radiation-induced PARTICLE lncRNA interacts with the transcription repressive complex proteins G9a and SUZ12 (subunit of PRC2). The interplay of PARTICLE with MAT2A, implicates this lncRNA in intercellular communication as well as a recruitment platform for gene silencing machineries through triplex formation in response to irradiation.
2015-03-19 | GSE67008 | GEO
Project description:The yeast E. dermatitidis is highly resistant to ionizing particle irradiation, and exposure to this stress elicits a transcriptomic response that is distinct from that induced by photonic irradiation. Melanin, in this organism, does not exhibit substantial control over this transcriptomic response, nor does it protect the cells from radiation-induced death under the conditions we tested. However, the strong response we observed here at the gene expression level inprovides insights into the unique types of damage that particle irradiation causes to fungal cells, allowing for future dissection of radiation source-specific resistance mechanisms.
2020-06-10 | GSE152116 | GEO
Project description:Human skin fibroblast mitochondrial depletion, 0.5 Gy alpha-particle
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Project description:The existence of a radiation bystander effect, in which non-irradiated cells respond to signals from irradiated cells, is well established. It raises concerns for the interpretation of risks from exposure to low doses of ionizing radiation. Sparse data exists about the bystander signaling mechanisms and the ability to transmit damaging effects both spatially and temporally. To understand early signaling and cellular changes in bystanders, we have measured global gene expression 30 minutes after direct and bystander exposure to alpha particle in primary human lung fibroblasts. Gene ontology and pathway analyses suggested that the earliest measured changes at 30 minutes after treatment are in cell structure, motility and adhesion categories and a significant number of genes belong to the category of inflammation and cell-to-cell communication. We investigated time course gene expression profiles of matrix metalloproteinases 1 and 3 (MMP1 and MMP3), chemokine ligands 2, 3 and 5 (CXCL2, CXCL3 and CXCL5), interleukins 1a, 1b, 6 and 33 (IL1A, IL1B, IL6 and IL33) growth differentiation factor 15 (GDF15) and superoxide dismutase2 (SOD2) by real time quantitative PCR. These encode proteins involved in cellular signaling via the NFkappaB pathway and time course of mRNA levels revealed an increased response at 30 minutes after irradiation followed by another wave at 4 to 6 hours. We also investigated protein modifications in the AKT-GSK-3 signaling pathway and found that in irradiated cells AKT and GSK3beta are hyper-phosphorylated at 30 minutes and this effect is maintained until 4 hours after exposure. In bystanders there is a similar response with a delay of 30 minutes. In irradiated cells, inactivated GSK3beta led to decreased phosphorylation of beta-catenin. Our results are the first to show that the radiation induced bystander signal can induce a widespread gene expression response as early as 30 minutes after exposure and that these changes are accompanied by protein modification of signaling modules such as AKT and GSK3beta. There are 12 total samples, 4 corresponding biological replicates of IMR90 cells that were not irradiated (control=C), irradiated (alpha=A) and bystander (B), cells were harvested 0.5 hr after treatment
2010-07-21 | E-GEOD-18760 | biostudies-arrayexpress