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

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

doi:10.1667/RR2220.1

Back

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

Journal article

Open access

Peer reviewed

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

Nukhet Aykin-Burns, Benjamin G Slane, Annie T Y Liu, Kjerstin M Owens, Malinda S O'Malley, Brian J Smith, Frederick E Domann and Douglas R Spitz

Radiation research, Vol.175(2), pp.150-158

02/2011

DOI: 10.1667/RR2220.1

PMCID: PMC3080019

PMID: 21268708

Files and links (1)

url

https://www.ncbi.nlm.nih.gov/pmc/articles/3080019View

Open Access

Abstract

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.

Cricetinae

Reactive Oxygen Species - metabolism

Cricetulus

Apoptosis - radiation effects

Membrane Proteins - genetics

Radiation Tolerance

Cells, Cultured

Mitochondria - metabolism

Animals

Membrane Proteins - physiology

Linear Energy Transfer

DNA Damage

Mutation

Details

Title: Subtitle: 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
Creators: Nukhet Aykin-Burns - Free Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA. nukhet-aykin-burns@uiowa.edu
Benjamin G Slane
Annie T Y Liu
Kjerstin M Owens
Malinda S O'Malley
Brian J Smith
Frederick E Domann
Douglas R Spitz
Resource Type: Journal article
Publication Details: Radiation research, Vol.175(2), pp.150-158
DOI: 10.1667/RR2220.1
PMID: 21268708
PMCID: PMC3080019
NLM abbreviation: Radiat Res
ISSN: 0033-7587
eISSN: 1938-5404
Publisher: United States
Grant note: P30 CA086862-01 / NCI NIH HHS T32 CA078586 / NCI NIH HHS R01-CA115438 / NCI NIH HHS T32-CA078586 / NCI NIH HHS R01 CA115438-02 / NCI NIH HHS T32 CA078586-09 / NCI NIH HHS R01 CA115438 / NCI NIH HHS P30-CA086862 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 02/2011
Academic Unit: Pathology; Biostatistics; Surgery; Radiation Oncology; Holden Comprehensive Cancer Center
Record Identifier: 9983997479302771

Metrics

16 Record Views

28 Times Cited - Web of Science