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

[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.

[学科分类] 生物化学/生物物理

[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