Oxidative DNA damage by hyperglycemia-related aldehydes and its marked enhancement by hydrogen peroxide |
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Authors: | Murata Mariko Mizutani Mika Oikawa Shinji Hiraku Yusuke Kawanishi Shosuke |
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Institution: | Department of Environmental and Molecular Medicine, Mie University School of Medicine, 2-174, Edobashi, Tsu, Mie 514-8507, Japan. |
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Abstract: | 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. |
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