Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Time-varying expression data from WI38 cell lines that were exposed to a challenge dose with or without a priming dose

ABSTRACT: The purpose of this experiment is to elucidate temporal activities and biological processes that can be inferred in response to a 200cGy challenging dose with or without a 10 cGy priming dose in embryonic human fibroblasts The experiment is designed around the human diploid embryonic lung fibroblast cell line WI38 (TP53 proficient), which was grown as a monolayer (2D) under physiological cell culture conditions (3% O2; 10% CO2). Cells are exposed to 2Gy (e.g., the challenge dose) of ionizing radiation (160 kV X-rays) with or without a priming dose of 10cGy (e.g., the adaptive dose) 4 hours prior to the challenge dose. Three biological replicates for each treatment group (e.g., with and without the priming dose) were collected 1, 2, 4 and 8 hours after the challenge dose. The time course was selected on the basis of our prior research on early response to ionizing radiation [1,2]. Purified total cellular RNA was extracted using an RNeasy Mini Kit (Qiagen) and quantified for Affymetrix microarray analysis using Human Gene 1.0 ST Array. Robust multi-array analysis (RMA) was performed to normalize data collected from the different samples. Samples were examined for quality control using the NUSE protocol. Reference [1] Groesser T. et al., Int J of Radiation Research, 2011. 87(7): p. 696-710. Reference [2] Han J. et al., Microscopy, 2010. 241(3): p. 315-326

ORGANISM(S): Homo sapiens

SUBMITTER: Bahram Parvin

PROVIDER: E-GEOD-37668 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The growing number of particle treatment facilities worldwide and patients treated with particles instead of X-rays marks the upcoming rearrangement of modern radiotherapy. Especially for tumors being difficult to access and for tumors that are resistant to conventional X-ray treatment particle radiotherapy is a beneficial technology. At the Heidelberg Ion Beam Therapy Center (HIT) patients are treated with this technology since 2009 as it offers clear benefits. Contrary to X-rays, which show an exponential dose decrease (after reaching electron equilibrium) with increasing tissue depth, charged particles deposit most of their energy to a small region within the tissue with a sharp dose fall-off after the so-called Bragg peak. This precise dose localization enables further dose escalation within the tumor while sparing healthy tissue. Besides physical advantages, particle radiotherapy offers additional biological advantages. In radiobiology, the term relative-biological effectiveness (RBE) is defined as the ratio of X-rays dose to an alternative irradiation modality dose which produce the same biological effect (e.g. survival or number of DSBs). While protons have a relative biological effectiveness (RBE) comparable to X-rays, carbon ions are more effective in inducing DNA damage(1, 2) and are therefore especially useful for radioresistant tumors. This is due to the fact, that carbon ions induce clustered and direct DNA damage, which is considered to be less dependent on cell cycle stage, oxygen level, genetic background and hinders DNA repair mechanisms(3–6). Nevertheless, their exact mode of action and cellular mechanisms are largely unknown. We show the first comprehensive proteomic and phosphoproteomic study elucidating the cellular response to treatment with protons, carbon ions and X-rays. We found that 2h after treatment with these radiations negligible regulation occurred at protein expression level. But 181 phosphorylation sites were deregulated by ionizing radiation contributing mainly to DNA damage response functionalities. Interestingly we found 55 phosphorylation sites being differentially regulated between the radiations. Here, we observed protons and carbon ions producing equal cellular response whereas X-rays show altered regulation for certain phosphorylation sites. A subset of 28 phosphorylation sites being involved in the DNA damage response or differentially regulated between the ionizing radiations was selected for result confirmation.

Project description:Measuring global gene expression using cDNA or oligonucleotide microarrays is an effective approach to understanding the complex mechanisms of the effects of radiation. However, few studies have been carried out that investigate gene expression in vivo after prolonged exposure to low-dose-rate radiation. In this study, C57BL/6J mice were continuously irradiated with ?-rays for 485 days at dose-rates of 0.032 – 13 ?Gy/min. Gene expression profiles in the kidney and testis from irradiated and unirradiated mice were analyzed, and differentially expressed genes were identified. A combination of pathway analysis and hierarchical clustering of differentially expressed genes revealed that expression of genes involved in mitochondrial oxidative phosphorylation was elevated in the kidney after irradiation at the dose-rates of 0.65 ?Gy/min and 13 ?Gy/min. Expression of cell cycle-associated genes was not profoundly modulated in the kidney, in contrast to the response to acute irradiation, suggesting a threshold in the dose-rate for modulation of the expression of cell cycle-related genes in vivo following exposure to radiation. We demonstrated that changes to the gene expression profile in the testis were largely different from those in the kidney. The Gene Ontology categories “DNA metabolism”, “response to DNA damage” and “DNA replication” overlapped significantly with the clusters of genes whose expression decreased with an increase in the dose-rate to the testis. These observations provide a fundamental insight into the organ-specific responses to low-dose-rate radiation. Key Words: kidney, low-dose-rate, radiation, microarray, mitochondrial oxidative phosphorylation, testis 3 biological replicates for each experimental group were analysed. GSE14290_Kidney_raw_data.csv contains the raw data for GSM357146, GSM357425, GSM357426, GSM357452 to GSM357460. GSE14290_Testis_raw_data.csv contains the raw data for GSM357471 to GSM357482. In these files, the sample identifiers are included in the column headers.

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Time-varying expression data from WI38 cell lines that were exposed to a challenge dose with or without a priming dose

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