| Sensitivity to low-dose/low-LET ionizing radiation in mammalian cells harboring mutations in succinate dehydrogenase subunit C is governed by mitochondria-derived reactive oxygen species. | |
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MedLine Citation:
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PMID: 21268708 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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It has been hypothesized that ionizing radiation-induced disruptions in mitochondrial O₂ metabolism lead to persistent heritable increases in steady-state levels of intracellular superoxide (O₂(•U+2212)) and hydrogen peroxide (H₂O₂) that contribute to the biological effects of radiation. Hamster fibroblasts (B9 cells) expressing a mutation in the gene coding for the mitochondrial electron transport chain protein succinate dehydrogenase subunit C (SDHC) demonstrate increases in steady-state levels of O₂•- and H₂O₂. When B9 cells were exposed to low-dose/low-LET radiation (5-50 cGy), they displayed significantly increased clonogenic cell killing compared with parental cells. Clones derived from B9 cells overexpressing a wild-type human SDHC (T4, T8) demonstrated significantly increased surviving fractions after exposure to 5-50 cGy relative to B9 vector controls. In addition, pretreatment with polyethylene glycol-conjugated CuZn superoxide dismutase and catalase as well as adenoviral-mediated overexpression of MnSOD and/or mitochondria-targeted catalase resulted in significantly increased survival of B9 cells exposed to 10 cGy ionizing radiation relative to vector controls. Adenoviral-mediated overexpression of either MnSOD or mitochondria-targeted catalase alone was equally as effective as when both were combined. These results show that mammalian cells over expressing mutations in SDHC demonstrate low-dose/low-LET radiation sensitization that is mediated by increased levels of O₂•- and H₂O₂. These results also support the hypothesis that mitochondrial O₂•- and H₂O₂ originating from SDH are capable of playing a role in low-dose ionizing radiation-induced biological responses. |
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Authors:
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Nukhet Aykin-Burns; Benjamin G Slane; Annie T Y Liu; Kjerstin M Owens; Malinda S O'Malley; Brian J Smith; Frederick E Domann; Douglas R Spitz |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-11-17 |
Journal Detail:
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Title: Radiation research Volume: 175 ISSN: 1938-5404 ISO Abbreviation: Radiat. Res. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-27 Completed Date: 2011-03-03 Revised Date: 2012-10-09 |
Medline Journal Info:
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Nlm Unique ID: 0401245 Medline TA: Radiat Res Country: United States |
Other Details:
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Languages: eng Pagination: 150-8 Citation Subset: IM; S |
Affiliation:
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Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA. nukhet-aykin-burns@uiowa.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / radiation effects Cells, Cultured Cricetinae Cricetulus DNA Damage Linear Energy Transfer* Membrane Proteins / genetics, physiology* Mitochondria / metabolism* Mutation* Radiation Tolerance* Reactive Oxygen Species / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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P30 CA086862/CA/NCI NIH HHS; P30 CA086862-01/CA/NCI NIH HHS; P30-CA086862/CA/NCI NIH HHS; R01 CA115438-02/CA/NCI NIH HHS; R01-CA115438/CA/NCI NIH HHS; T32 CA078586-09/CA/NCI NIH HHS; T32-CA078586/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Membrane Proteins; 0/Reactive Oxygen Species; 0/SDHC protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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