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Acute high dose X-irradiation-induced genomic changes in a lung tumor cell line

ABSTRACT: Accidents with ionizing radiation (IR) often involve acute high dose exposures that can lead to acute radiation syndrome and late effects. IR can induce genomic lesions, cell death or carcinogenesis. Here, we investigated acute IR-induced cellular genomic signatures at the genome wide level. After exposing the adenocarcinoma cell line A549 to an acute 6 Gy 240 kV X-Ray dose, four surviving clonogenic cells were recovered by minimal dilution and further expanded and analyzed by cytogenetics, chromosome painting and tiling-path array CGH, with the non-irradiated clone0 serving as control. It was found that acute X-ray exposure induced changes in modal chromosome number and specific translocations in the four irradiation surviving clones. Furthermore, clone4 displayed an increased radiosensitivity at D > 5 Gy. Array CGH disclosed unique and recurrent genomic changes, predominantly gains, and disclosed fragile sites FRA3B and FRA16D as preferential regions of genomic alterations in all irradiated clones, which likely relates to irradiation-induced genomic stress. Gene expression analysis revealed a specific profile of 364 genes in clone4, of which p53 pathway genes may contribute to its increased radiosensitivity. IR-induced genomic changes AND fragile site expression highlight the capacity of a single acute radiation exposure to resculpture the genome of tumor cells by inflicting genomic stress. Gene expression in A549 cell line was analysed after exposure to 6Gy X-rays at a dose rate of 1Gy/min.

ORGANISM(S): Homo sapiens

SUBMITTER: Artur Muradyan

PROVIDER: E-GEOD-24876 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Acute high dose X-irradiation-induced genomic changes in a lung tumor cell line

Project description:Accidents with ionizing radiation (IR) often involve acute high dose exposures that can lead to acute radiation syndrome and late effects. IR can induce genomic lesions, cell death or carcinogenesis. Here, we investigated acute IR-induced cellular genomic signatures at the genome wide level. After exposing the adenocarcinoma cell line A549 to an acute 6 Gy 240 kV X-Ray dose, four surviving clonogenic cells were recovered by minimal dilution and further expanded and analyzed by cytogenetics, chromosome painting and tiling-path array CGH, with the non-irradiated clone0 serving as control. It was found that acute X-ray exposure induced changes in modal chromosome number and specific translocations in the four irradiation surviving clones. Furthermore, clone4 displayed an increased radiosensitivity at D > 5 Gy. Array CGH disclosed unique and recurrent genomic changes, predominantly gains, and disclosed fragile sites FRA3B and FRA16D as preferential regions of genomic alterations in all irradiated clones, which likely relates to irradiation-induced genomic stress. Gene expression analysis revealed a specific profile of 364 genes in clone4, of which p53 pathway genes may contribute to its increased radiosensitivity. IR-induced genomic changes AND fragile site expression highlight the capacity of a single acute radiation exposure to resculpture the genome of tumor cells by inflicting genomic stress.

2011-02-04 | GSE24876 | GEO

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Expression data from 5 human cell lines exposed to IR (5 Gy)

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2011-07-31 | E-GEOD-30240 | biostudies-arrayexpress

p97/VCP inhibition radiosensitises cancer cells through excessive MRE11-dependent DNA end resection

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Coordinated regulation of MAPK signaling pathway and microRNA in response to ionizing radiation in lung cancer cells

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2012-01-28 | E-GEOD-35372 | biostudies-arrayexpress

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Project description:Humans are exposed to ionizing radiation (IR) from background radiation, medical treatments, occupational and accidental exposures. IR causes profound changes in transcription. Transcription is a primary process where protein amount and function can be regulated. One aspect of the transcriptional IR response that little is known about on a whole genome basis is alternative transcription. These investigations focus on the response to IR at the exon level in human cells but also at the whole gene level. Whole genome exon arrays were utilized to comprehensively characterize radiation-induced transcriptional expression products in two human cell types, namely EBV-transformed lymphoblast and primary fibroblast cell lines. 12 human primary fibroblast cell lines and 12 primary lymphoblast cell line samples were used for two doses (0 and 10 Gy) and two time points (0 and 4hr). Additional doses ( 1 Gy, 2 Gy, 5 Gy, and 20 Gy) and time points ( 1hr, 2hr, 8hr, 24hr and 48hr) were assessed in four lymphoblast cell lines and four primary fibroblasts.

2011-05-02 | E-GEOD-26841 | biostudies-arrayexpress

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