Oxidative DNA damage by hyperglycemia-related aldehydes and its marked enhancement by hydrogen peroxide.
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.
Department of Environmental and Molecular Medicine, Mie University School of Medicine, 2-174, Edobashi, Tsu, Mie 514-8507, Japan.
Mariko
M
Murata
Mika
M
Mizutani
Shinji
S
Oikawa
Yusuke
Y
Hiraku
Shosuke
S
Kawanishi
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000447:Aldehydes / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology; D004249:DNA Damage; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000494:pharmacology; D003849:Deoxyguanosine / Q000031:analogs & derivatives*; D048909:Diabetes Complications; D004357:Drug Synergism; D005985:Glyceraldehyde / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006943:Hyperglycemia / Q000378:metabolism*; D009369:Neoplasms / Q000209:etiology; D010084:Oxidation-Reduction
D000447:Aldehydes; D005985:Glyceraldehyde; D003300:Copper; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003847:Deoxyglucose; D006861:Hydrogen Peroxide; C016350:3-deoxyglucosone; D003849:Deoxyguanosine