Document Detail

A mutation in the SDHC gene of complex II increases oxidative stress, resulting in apoptosis and tumorigenesis.
MedLine Citation:
PMID:  15665296     Owner:  NLM     Status:  MEDLINE    
Intracellular oxidative stress from mitochondria is thought to be important in carcinogenesis and tumorigenesis, but direct experimental proof is limited. In this study, a transgenic mouse cell line (SDHC E69) with a mutated SDHC gene (a subunit of complex II in the electron transport chain) was constructed to test this question. The SDHC E69 cells overproduced superoxide anion (O(2)(-)) from mitochondria, had elevated cytoplasmic carbonyl proteins and 8-OH-deoxyguanine in their DNA as well as significantly higher mutation frequencies than wild type. There were many apoptotic cells in this cell line, as predicted by the observed increase in caspase 3 activity, decrease in mitochondrial membrane potential, and structural changes in their mitochondria. In addition, some cells that escaped from apoptosis underwent transformation, as evidenced by the fact that SDHC E69 cells caused benign tumors when injected under the epithelium of nude mice. These results underscore the notion that mitochondrially generated oxidative stress can contribute to nuclear DNA damage, mutagenesis, and ultimately, tumorigenesis.
Takamasa Ishii; Kayo Yasuda; Akira Akatsuka; Okio Hino; Philip S Hartman; Naoaki Ishii
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  65     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2005-01-24     Completed Date:  2005-03-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  203-9     Citation Subset:  IM    
Department of Molecular Life Science, Tokai University School of Medicine, Kanagawa, Japan.
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MeSH Terms
Amino Acid Sequence
Apoptosis / genetics*
Bacterial Proteins / genetics
Base Sequence
Caspase 3
Caspases / metabolism
Cloning, Molecular
DNA Primers
Deoxyguanosine / analogs & derivatives*,  analysis
Gene Frequency
Membrane Proteins / genetics*
Mice, Transgenic
Molecular Sequence Data
Neoplasms / enzymology,  genetics*
Oxidative Stress / physiology*
Polymerase Chain Reaction
Sequence Alignment
Sequence Homology, Amino Acid
Succinate Dehydrogenase / genetics
Superoxides / metabolism
Reg. No./Substance:
0/8-hydroxy-2'-deoxyguanosine; 0/Bacterial Proteins; 0/DNA Primers; 0/Membrane Proteins; 0/SDHC protein, human; 0/SdhC protein, bacteria; 11062-77-4/Superoxides; 961-07-9/Deoxyguanosine; EC Dehydrogenase; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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