Gene expression profiling of peripheral blood mononuclear cells (PBMCs) 8 hours after exposure to 1 Gy of carbon or iron ions
Ontology highlight
ABSTRACT: Under certain circumstances, humans can be exposed to ionizing radiation from heavy ions. Examples are cancer patients undergoing particle therapy (e.g. carbon ions) or astronauts in deep Space missions (iron ions which contribute for a large fraction to the possible health effects of cosmic radiation because of their high ionisation power). Understanding the differences in the cellular response to low- and high-LET radiation is important in order to adequately model risk estimates based on extrapolations from low-LET exposures. To address this need, we compared the transcriptional profiles of freshly isolated peripheral blood mononuclear cells after exposure to 1 Gy of X-rays, iron ions or carbon ions. Data of X-ray exposure have been submitted in E-MTAB-3463: https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-3463/.
Project description:In recent years there is a growing epidemiological indication of excess risk of cardiovascular disease at low doses of ionizing radiation without a clear-cut threshold. It is proposed that damage to the vascular endothelium is critical in radiation-related cardiovascular diseases. In order to identify and better understand the underlying molecular mechanisms of high LET (Fe ions) and low LET (X-ray) radiation on endothelial cells, we performed a microarray analysis on immortalized human coronary artery endothelial cells irradiated with 2.00 Gy and compared them with sham-irradiated samples. RNA was extracted at different time points after irradiation (1 day, 7 days).
Project description:Normal lung tissue tolerance constitutes a limiting factor in delivering the required dose of radiotherapy to cure thoracic and chest wall malignancies. Patient genetic predisposition, the volume of irradiated lung and combination regimens consisting of concurrent chemotherapy are correlated with increased risk of radiation induced toxicity in lung. The main purpose of this study is to investigate dose-response regulations of mouse lung irradiation based on a comprehensive dose-escalation program, for a better understanding of molecular mechanism governing radiation induced lung fibrosis by high-LET carbon-ions versus conventional low-LET X-ray.
Project description:The time factor in the development of radiation induced lung fibrosis is important but not well characterized so far. This study was to investigate the time series of acute-, subacute-, early and late- timepoints after exposure with low-LET photons versus proton versus and high-LET carbon-ions. The role of CTGF inhibitor in modulating inflammation related signaling pathways were also studied at the acute timepoints. The potential mechanisms underlining the time-dependent progression of inflammatory and fibrotic response is to be illustrated in the present study.
Project description:Endostatin is a naturally occurring 183-amino acid proteolytic fragment of collagen XVIII that localizes in the basement membrane around blood vessels. The anti-tumor properties of this protein have been extensively described, demarcating endostatin as an endogenous inhibitor of angiogenesis. Further, it supresses many signaling cascades such as pro-inflammatory NF-κB, coagulation and adhesion cascades. Yamaguchi et al. reported that endostatin via its C-terminal domain (E4 peptide) has elicit anti-fibrosis effects. However, the zinc binding domain has been previously confined to the N terminus (endostatin mP1 peptide) and was critical to numerous functions of the molecule. The present study aimed to better understand the impact of oligomerization (Fc-Endostatin) as well as N- vs. C-terminal fragments of endostatin (mP1, CE4) on modulating radiation-induced lung fibrosis. Mice were treated with Fc-endostatin (Fc-Endo), N-terminus endostatin peptide (mP1) or C-terminus endostatin E4 peptide (CE4) combined with photon 20 Gy or carbon-ions 12.5 Gy whole thoracic irradiation
Project description:This SuperSeries is composed of the following subset Series: GSE16518: Response of human lymphoblastoid cells to HZE (iron ions) or gamma-rays GSE16519: Response of human lymphoblastoid cells to activated medium Refer to individual Series
Project description:Transcriptional profiling of human lymphoblastoid TK6 cells comparing mock irradiated cells with cells exposed 24 hours previously to 1.67 Gy HZE (1 GeV/amu iron ions accelerated at the NASA Space Research Laboratory (NSRL) of Brookhaven National Laboratory) or 2.5 Gy 137Cs gamma rays. TK6 cells were mock irradiated or exposed to HZE or gamma-rays, and RNA was harvested 24 hours later. 3 biological replicates were independently grown and harvested during three different runs at the NSRL. One replicate per array.
Project description:Transcriptional profiling of human lymphoblastoid TK6 cells comparing mock irradiaed cells resuspended in fresh untreated RPMI 1640 medium with cells resuspended in medium activated by exposure to 2.5 Gy HZE (1 GeV/amu iron ions accelerated at the NASA Space Research Laboratory (NSRL) of Brookhaven National Laboratory). Two-condition experiment, mock irradiated vs. cells exposed to activated medium. 3 biological replicates were independently grown and harvested during three different runs at the NSRL. One replicate per array.
Project description:The potential mechanisms of DNA-PKcs and its related signaling pathways in radiation-induced pulmonary toxicity is unclear. The current study utilized genetic engineering DNA-PKcs knockout mouse model, to investigate the molecular mechanisms after dose-response exposure of of the fractionated low-LET photon and high-LET carbon-ion exposure to the whole thorax.
Project description:The environment outside the Earth’s protective magnetosphere is a much more threatening and complex space environment. The dominant causes for radiation exposure, solar particle events and galactic cosmic rays, contain high-energy protons. In space, astronauts need healthy and highly functioning cognitive abilities, of which the hippocampus plays a key role. Therefore, understanding the effects of 1H exposure on hippocampal-dependent cognition is vital for de-veloping mitigative strategies and protective countermeasures for future missions. To investi-gate these effects, we subjected 6-month-old female CD1 mice to 0.75 Gy fractionated 1H (250 MeV) whole-body irradiation at the NASA Space Radiation Laboratory. The cognitive perfor-mance of the mice was tested 3 months after irradiation using Y-maze and morris water maze tests. Both sham-irradiated and 1H-irradiated mice significantly preferred exploration of the novel arm compared to the familiar and start arms, indicating intact spatial and short-term memory. Both groups statistically spent more time in the target quadrant, indicating spatial memory retention. There were no significant differences in neurogenic and gliogenic cell counts after irradiation. In addition, proteomic analysis revealed no significant upregulation or down-regulation of proteins related to behavior, neurological disease, or neural morphology. Our data suggests 1H exposure does not impair hippocampal-dependent spatial or short-term memory in female mice.
Project description:The aim of our study is to investigate and compare the effects of carbon and photon irradiation on microvascular endothelial cells. Therefore we irradiated human pulmonary microvascular endothelial cells (HPMEC) with either 2Gy Carbon or 6Gy Photon (bioequivalent doses) and performed microarray analysis both 2 hours (short-term effect) and 6 days (long-term effects) after irradiation. All experiments were performed in 3 biological replicates.