Oxidative DNA damage by hyperglycemia‐related aldehydes and its marked enhancement by hydrogen peroxide

FEBS Letters

Mizutani, Mika¹  Oikawa, Shinji¹  Kawanishi, Shosuke¹  Murata, Mariko¹  Hiraku, Yusuke¹ 

[1] Department of Environmental and Molecular Medicine, Mie University School of Medicine, 2-174, Edobashi, Tsu, Mie 514-8507, Japan

关键词: Diabetes mellitus;    Hyperglycemia;    Oxidative DNA damage;    Glyceraldehyde;    3-Deoxyglucosone;    3-DG;    3-deoxyglucosone;    GA;    glyceraldehyde;    GA3P;    glyceraldehyde 3-phosphate;    MG;    methylglyoxal;    AGE;    advanced glycated end-product;    8-oxodG;    8-oxo-7;    8-dihydro-2′-deoxyguanosine (also known as 8-hydroxy-2′-deoxyguanosine);    DTPA;    diethylenetriamine-N;    N;    N′;    N″;    N″-pentaacetic acid;    HPLC-ECD;    high performance liquid chromatography coupled with an electrochemical detector;    SOD;    superoxide dismutase;   

DOI  :  10.1016/S0014-5793(03)01129-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Increased risks of cancers and oxidative DNA damage have been observed in diabetic patients. Many endogenous aldehydes such as 3-deoxyglucosone and glyceraldehyde (GA) increase under hyperglycemic conditions. We showed that these aldehydes induced Cu(II)-mediated DNA damage, including 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) formation. GA had the strongest ability to damage DNA, and addition of low concentrations of H₂O₂ markedly enhanced the DNA damage. GA significantly increased 8-oxodG formation in human cultured cells (HL-60), and H₂O₂ enhanced it. We conclude that oxidative DNA damage by hyperglycemia-related aldehydes, especially GA, and marked enhancement of DNA damage by H₂O₂ may participate in diabetes-associated carcinogenesis.

【 授权许可】

Unknown