Vitamin C-Induced Decomposition of Lipid Hydroperoxides to Endogenous Genotoxins

作者：Seon Hwa Lee, Tomoyuki Oe, Ian A. Blair · 发表于：Science · 年份：2001 · DOI：10.1126/science.1059501 · 被引用次数：419 · 研究领域：Antioxidant Activity and Oxidative Stress、Vitamin C and Antioxidants Research、Free Radicals and Antioxidants

Epidemiological data suggest that dietary antioxidants play a protective role against cancer. This has led to the proposal that dietary supplementation with antioxidants such as vitamin C (vit C) may be useful in disease prevention. However, vit C has proved to be ineffective in cancer chemoprevention studies. In addition, concerns have been raised over potentially deleterious transition metal ion-mediated pro-oxidant effects. We have now determined that vit C induces lipid hydroperoxide decomposition to the DNA-reactive bifunctional electrophiles 4-oxo-2-nonenal, 4,5-epoxy-2(E)-decenal, and 4-hydroxy-2-nonenal. The compound 4,5-Epoxy-2(E)-decenal is a precursor of etheno-2'-deoxyadenosine, a highly mutagenic lesion found in human DNA. Vitamin C-mediated formation of genotoxins from lipid hydroperoxides in the absence of transition metal ions could help explain its lack of efficacy as a cancer chemoprevention agent.