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  Acute high-dose X-radiation-induced genomic changes in A549 cells

Muradyan, A., Gilbertz, K., Stabentheiner, S., Klause, S., Madle, H., Meineke, V., et al. (2011). Acute high-dose X-radiation-induced genomic changes in A549 cells. Radiat Res, 175(6), 700-7. Retrieved from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21361782 http://www.bioone.org/doi/pdf/10.1667/RR2341.1.

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 Creators:
Muradyan, A.1, Author           
Gilbertz, K., Author
Stabentheiner, S., Author
Klause, S., Author
Madle, H., Author
Meineke, V., Author
Ullmann, R.2, Author           
Scherthan, H.3, Author           
Affiliations:
1Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              
2Molecular Cytogenetics (Reinhard Ullmann), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479645              
3Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              

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Free keywords: Cell Cycle/radiation effects; Cell Line, Tumor; Cell Survival/radiation effects; *Chromosome Aberrations; Comparative Genomic Hybridization; Gene Dosage/*radiation effects; Gene Expression/radiation effects; Genome, Human/*radiation effects; Genomic Instability/radiation effects; Humans; Radiation Tolerance; X-Rays
 Abstract: Accidents with ionizing radiation often involve single, acute high-dose exposures that can lead to acute radiation syndrome and late effects such as carcinogenesis. To study such effects at the cellular level, we investigated acute ionizing radiation-induced chromosomal aberrations in A549 adenocarcinoma cells at the genome-wide level by exposing the cells to an acute dose of 6 Gy 240 kV X rays. One sham-irradiated clone and four surviving irradiated clones were recovered by minimal dilution and further expanded and analyzed by chromosome painting and tiling-path array CGH, with the nonirradiated clone 0 serving as the control. Acute X-ray exposure induced specific translocations and changes in modal chromosome number in the four irradiated clones. Array CGH disclosed unique and recurrent genomic changes, predominantly losses, and revealed that the fragile sites FRA3B and FRA16D were preferential regions of genomic alterations in all irradiated clones, which is likely related to radioresistant S-phase progression and genomic stress. Furthermore, clone 4 displayed an increased radiosensitivity at doses >5 Gy. Pairwise comparisons of the gene expression patterns of all irradiated clones to the sham-irradiated clone 0 revealed an enrichment of the Gene Ontology term "M Phase" (P = 6.2 x 10(-7)) in the set of differentially expressed genes of clone 4 but not in those of clones 1-3. Ionizing radiation-induced genomic changes and fragile site expression highlight the capacity of a single acute radiation exposure to affect the genome of exposed cells by inflicting genomic stress.

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 Dates: 2011
 Publication Status: Published in print
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Title: Radiat Res
Source Genre: Journal
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Pages: - Volume / Issue: 175 (6) Sequence Number: - Start / End Page: 700 - 7 Identifier: ISSN: 1938-5404 (Electronic) 0033-7587 (Linking)