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维生素C导致的脂质过氧化物分解为内源性基因毒物 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. [引自Science 2001 Jun 15;292(5524):2083-6] |