Journal article
Mutation of succinate dehydrogenase subunit C results in increased O2.-, oxidative stress, and genomic instability
Cancer research (Chicago, Ill.), Vol.66(15), pp.7615-7620
08/01/2006
DOI: 10.1158/0008-5472.CAN-06-0833
PMID: 16885361
Abstract
Mutations in genes coding for succinate dehydrogenase (SDH) subunits are believed to contribute to cancer and aging, but the mechanism for this is unclear. Hamster fibroblasts expressing a mutation in SDH subunit C (SDHC; B9) showed 3-fold increases in dihydroethidine and dichlorodihydrofluorescein (CDCFH(2)) oxidation indicative of increased steady-state levels of O2(.-) and H2O2, increases in glutathione/glutathione disulfide (indicative of oxidative stress), as well as increases in superoxide dismutase activity, relative to parental B1 cells. B9 cells also showed characteristics associated with cancer cells, including aneuploidy, increases in glucose consumption, and sensitivity to glucose deprivation-induced cytotoxicity. Expression of wild-type (WT) human SDHC in B9 cells caused prooxidant production, glucose consumption, sensitivity to glucose deprivation-induced cytotoxicity, and aneuploidy to revert to the WT phenotype. These data show that SDHC mutations cause increased O2(.-) production, metabolic oxidative stress, and genomic instability and that mutations in genes coding for mitochondrial electron transport chain proteins can contribute to phenotypic changes associated with cancer cells. These results also allow for the speculation that DNA damage to genes coding for electron transport chain proteins could result in a "mutator phenotype" by increasing steady-state levels of O2(.-) and H2O2.
Details
- Title: Subtitle
- Mutation of succinate dehydrogenase subunit C results in increased O2.-, oxidative stress, and genomic instability
- Creators
- Benjamin G Slane - Free Radical and Radiation Biology Program, B180 Medical Laboratories, Department of Radiation Oncology, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USANùkhet Aykin-BurnsBrian J SmithAmanda L KalenPrabhat C GoswamiFrederick E DomannDouglas R Spitz
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.66(15), pp.7615-7620
- Publisher
- United States
- DOI
- 10.1158/0008-5472.CAN-06-0833
- PMID
- 16885361
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Grant note
- P30 CA 086862 / NCI NIH HHS R01 CA 100045 / NCI NIH HHS F32 CA 110611 / NCI NIH HHS R01 CA 111365 / NCI NIH HHS P01 CA 66081 / NCI NIH HHS
- Language
- English
- Date published
- 08/01/2006
- Academic Unit
- Pathology; Biostatistics; Surgery; Radiation Oncology; Holden Comprehensive Cancer Center
- Record Identifier
- 9983997466402771
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