8-hydroxy-2--deoxyguanosine and 3-deoxyglucosone

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.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Copper; Deoxyglucose; Deoxyguanosine; Diabetes Complications; DNA Damage; Drug Synergism; Glyceraldehyde; HL-60 Cells; Humans; Hydrogen Peroxide; Hyperglycemia; Neoplasms; Oxidation-Reduction