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Gene expression variation in lymphocyte subpopulations in response to low dose of ionizing radiations

ABSTRACT: Lymphocytes are the standard cell of a majority of biodosimetry approaches because of their availability and radiosensitivity. But progresses remain to be performed to bring down the minimum threshold of dose sensitivity. To find a lymphocyte subtype able to respond to low doses of ionizing radiation, we examined gene expression variations in different lymphocyte subpopulations using the microarray technology. Blood samples were independently exposed to 0, 0.05 and 0.5 Gray of ionizing radiations. Three and 24 hours after exposure, CD56+, CD4+ and CD8+ cells were negatively isolated. RNA from each condition was competitively hybridized on oligonucleotide microarrays. Keywords: Dose response, stress response, cell type comparison

ORGANISM(S): Homo sapiens

PROVIDER: GSE6978 | GEO | 2008/02/01

SECONDARY ACCESSION(S): PRJNA99285

REPOSITORIES: GEO

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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.

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Gene expression variation in lymphocyte subpopulations in response to low dose of ionizing radiations

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