Document Detail


UV-irradiation induces oxidative damage to mitochondrial DNA primarily through hydrogen peroxide: analysis of 8-oxodGuo by HPLC.
MedLine Citation:
PMID:  17050167     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Roles of reactive oxygen species (ROS) in damage to mitochondrial DNA (mtDNA) following ultraviolet (UV)-irradiation were investigated in the human hepatoma cell line SK-HEP-1. We altered the intracellular status of ROS by the overexpression of manganese superoxide dismutase (MnSOD) and/or catalase. Using HPLC, we analyzed 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), known as a marker of damage to DNA molecules. UV-irradiation resulted in the accumulation of 8-oxodGuo in these cells. The overexpression of MnSOD enhanced the accumulation of 8-oxodGuo by UV. The co-overexpression of catalase inhibited the accumulation of 8-oxodGuo by UV in MnSOD-transfectants. The overexpression of MnSOD reduced the colony forming capacity in SK-HEP-1 cells and the co-overexpression of catalase with MnSOD stimulated the capacity compared to control. UV-irradiation inhibited the colony forming capacity in these cells; no difference was observed among the capacities of control, MnSOD- and catalase-transfectants. However, the overexpression of MnSOD/catalase significantly rescued the reduction of colony forming capacity by UV-irradiation. Our results suggest that the accumulation of hydrogen peroxide plays a key role in the oxidative damage to mtDNA of UV-irradiated cells, and also that the overexpression of both MnSOD and catalase reduces the mtDNA damage and blocks the growth inhibition by UV. Our results also indicate that the increased activity of MnSOD may lead to a toxic effect on mtDNA by UV-irradiation.
Authors:
Daisaku Takai; Sang-Hee Park; Yasunari Takada; Shizuko Ichinose; Masanobu Kitagawa; Makoto Akashi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Free radical research     Volume:  40     ISSN:  1071-5762     ISO Abbreviation:  Free Radic. Res.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-10-19     Completed Date:  2007-02-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9423872     Medline TA:  Free Radic Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  1138-48     Citation Subset:  IM    
Affiliation:
Department of Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba, Japan.
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MeSH Terms
Descriptor/Qualifier:
Antioxidants / pharmacology
Carcinoma, Hepatocellular / metabolism
Catalysis
Cell Line, Tumor
Chelating Agents / pharmacology
Chromatography, High Pressure Liquid / methods*
DNA Damage
DNA, Mitochondrial / chemistry*
Deoxyguanosine / analogs & derivatives*,  analysis,  chemistry
Humans
Hydrogen Peroxide / pharmacology
Microscopy, Electron, Transmission
Microscopy, Immunoelectron
Oxidative Stress
Ultraviolet Rays
Chemical
Reg. No./Substance:
0/8-hydroxy-2'-deoxyguanosine; 0/Antioxidants; 0/Chelating Agents; 0/DNA, Mitochondrial; 7722-84-1/Hydrogen Peroxide; 961-07-9/Deoxyguanosine

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