Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aldehydes / chemistry
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Aldehydes / metabolism
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Antioxidants / chemistry
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Ascorbic Acid / adverse effects
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Ascorbic Acid / chemistry
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Ascorbic Acid / metabolism
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Ascorbic Acid / pharmacology*
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Buffers
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Copper / pharmacology
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Cyclooxygenase 1
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Cyclooxygenase 2
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DNA Adducts / chemistry
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DNA Adducts / metabolism
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DNA Damage
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Epoxy Compounds / chemistry
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Epoxy Compounds / metabolism
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Ferrous Compounds / pharmacology
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Humans
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Isoenzymes / metabolism
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Linoleic Acids / chemistry*
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Linoleic Acids / metabolism
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Lipid Peroxides / chemistry*
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Lipid Peroxides / metabolism
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Membrane Proteins
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Metals / pharmacology
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Mutagens / chemistry*
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Mutagens / metabolism
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Oxidants / adverse effects
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Oxidants / chemistry
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Oxidants / metabolism
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Oxidants / pharmacology
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Oxidation-Reduction
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Prostaglandin-Endoperoxide Synthases / metabolism
Substances
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4,5-epoxy-2-decenal
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4-oxo-2-nonenal
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Aldehydes
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Antioxidants
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Buffers
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DNA Adducts
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Epoxy Compounds
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Ferrous Compounds
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Isoenzymes
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Linoleic Acids
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Lipid Peroxides
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Membrane Proteins
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Metals
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Mutagens
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Oxidants
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13-hydroperoxy-9,11-octadecadienoic acid
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Copper
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Cyclooxygenase 1
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Cyclooxygenase 2
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PTGS1 protein, human
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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4-hydroxy-2-nonenal
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Ascorbic Acid