Vitamin C-induced Decomposition of Lipid Hydroperoxides to Endogenous Genotoxins

Science. 2001 Jun 15;292(5524):2083-6. doi: 10.1126/science.1059501.

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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aldehydes / chemistry
  • Aldehydes / metabolism
  • Antioxidants / chemistry
  • Ascorbic Acid / adverse effects
  • Ascorbic Acid / chemistry
  • Ascorbic Acid / metabolism
  • Ascorbic Acid / pharmacology*
  • Buffers
  • Copper / pharmacology
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • DNA Adducts / chemistry
  • DNA Adducts / metabolism
  • DNA Damage
  • Epoxy Compounds / chemistry
  • Epoxy Compounds / metabolism
  • Ferrous Compounds / pharmacology
  • Humans
  • Isoenzymes / metabolism
  • Linoleic Acids / chemistry*
  • Linoleic Acids / metabolism
  • Lipid Peroxides / chemistry*
  • Lipid Peroxides / metabolism
  • Membrane Proteins
  • Metals / pharmacology
  • Mutagens / chemistry*
  • Mutagens / metabolism
  • Oxidants / adverse effects
  • Oxidants / chemistry
  • Oxidants / metabolism
  • Oxidants / pharmacology
  • Oxidation-Reduction
  • Prostaglandin-Endoperoxide Synthases / metabolism

Substances

  • 4,5-epoxy-2-decenal
  • 4-oxo-2-nonenal
  • Aldehydes
  • Antioxidants
  • Buffers
  • DNA Adducts
  • Epoxy Compounds
  • Ferrous Compounds
  • Isoenzymes
  • Linoleic Acids
  • Lipid Peroxides
  • Membrane Proteins
  • Metals
  • Mutagens
  • Oxidants
  • 13-hydroperoxy-9,11-octadecadienoic acid
  • Copper
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • 4-hydroxy-2-nonenal
  • Ascorbic Acid