PMID- 16885361
OWN - NLM
STAT- MEDLINE
DCOM- 20060928
LR  - 20150123
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 66
IP  - 15
DP  - 2006 Aug 1
TI  - Mutation of succinate dehydrogenase subunit C results in increased O2.-, 
      oxidative stress, and genomic instability.
PG  - 7615-20
AB  - 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.
FAU - Slane, Benjamin G
AU  - Slane BG
AD  - 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, USA.
FAU - Aykin-Burns, Nukhet
AU  - Aykin-Burns N
FAU - Smith, Brian J
AU  - Smith BJ
FAU - Kalen, Amanda L
AU  - Kalen AL
FAU - Goswami, Prabhat C
AU  - Goswami PC
FAU - Domann, Frederick E
AU  - Domann FE
FAU - Spitz, Douglas R
AU  - Spitz DR
LA  - eng
GR  - F32 CA 110611/CA/NCI NIH HHS/United States
GR  - P01 CA 66081/CA/NCI NIH HHS/United States
GR  - P30 CA 086862/CA/NCI NIH HHS/United States
GR  - R01 CA 100045/CA/NCI NIH HHS/United States
GR  - R01 CA 111365/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Membrane Proteins)
RN  - 0 (SDHC protein, human)
RN  - 11062-77-4 (Superoxides)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - Cricetinae
MH  - Cricetulus
MH  - Fibroblasts/enzymology/metabolism
MH  - Genomic Instability/*physiology
MH  - Humans
MH  - Lung/cytology
MH  - Membrane Proteins/*genetics/metabolism
MH  - Molecular Sequence Data
MH  - Oxidative Stress
MH  - Superoxides/*metabolism
MH  - Transfection
EDAT- 2006/08/04 09:00
MHDA- 2006/09/29 09:00
CRDT- 2006/08/04 09:00
PHST- 2006/08/04 09:00 [pubmed]
PHST- 2006/09/29 09:00 [medline]
PHST- 2006/08/04 09:00 [entrez]
AID - 66/15/7615 [pii]
AID - 10.1158/0008-5472.CAN-06-0833 [doi]
PST - ppublish
SO  - Cancer Res. 2006 Aug 1;66(15):7615-20. doi: 10.1158/0008-5472.CAN-06-0833.