Vitamin C-induced decomposition of lipid hydroperoxides to endogenous genotoxins

Epidemiological data suggest that dietary antioxidants play a protective ro le against cancer. This has led to the proposal that dietary supplementatio n with antioxidants such as vitamin C (vit C) may be useful in disease prev ention. However, vit C has proved to be ineffective in cancer chemopreventi on studies. In addition, concerns have been raised over potentially deleter ious transition metal ion-mediated pro-oxidant effects. We have now determi ned that vit C induces lipid hydroperoxide decomposition to the DNA-reactiv e bifunctional electrophiles 4-oxo-2-nonenal, 4,5-epoxy-2(E)-decenal, and 4 -hydroxy-2-non-enal, The compound 4,5-Epoxy-2(E)-decenal is a precursor of etheno-2'-deoxyadenosine, a highly mutagenic lesion found in human DNA. Vit amin C-mediated formation of genotoxins from lipid hydroperoxides in the ab sence of transition metal ions could help explain its lack of efficacy as a cancer chemoprevention agent.