Document Detail

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.
MedLine Citation:
PMID:  21268708     Owner:  NLM     Status:  MEDLINE    
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.
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:
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:
Title:  Radiation research     Volume:  175     ISSN:  1938-5404     ISO Abbreviation:  Radiat. Res.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-27     Completed Date:  2011-03-03     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  0401245     Medline TA:  Radiat Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  150-8     Citation Subset:  IM; S    
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MeSH Terms
Apoptosis / radiation effects
Cells, Cultured
DNA Damage
Linear Energy Transfer*
Membrane Proteins / genetics,  physiology*
Mitochondria / metabolism*
Radiation Tolerance*
Reactive Oxygen Species / metabolism*
Grant Support
P30 CA086862/CA/NCI NIH HHS; P30 CA086862-01/CA/NCI NIH HHS; P30-CA086862/CA/NCI NIH HHS; R01 CA115438/CA/NCI NIH HHS; R01 CA115438-02/CA/NCI NIH HHS; R01-CA115438/CA/NCI NIH HHS; T32 CA078586/CA/NCI NIH HHS; T32 CA078586-09/CA/NCI NIH HHS; T32-CA078586/CA/NCI NIH HHS
Reg. No./Substance:
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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