Vitamin C-Induced Decomposition of Lipid Hydroperoxides to Endogenous Genotoxins
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- 15 June 2001
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 292 (5524) , 2083-2086
- https://doi.org/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.Keywords
This publication has 28 references indexed in Scilit:
- The Reactive Oxygen Species- and Michael Acceptor-inducible Human Aldo-Keto Reductase AKR1C1 Reduces the α,β-Unsaturated Aldehyde 4-Hydroxy-2-nonenal to 1,4-Dihydroxy-2-noneneJournal of Biological Chemistry, 2001
- Potential Problems of Ascorbate and Iron Supplementation: Pro-Oxidant Effect in Vivo?Biochemical and Biophysical Research Communications, 2000
- 4-Hydroxy-2-nonenal, the End Product of Lipid Peroxidation, Is a Specific Inducer of Cyclooxygenase-2 Gene ExpressionBiochemical and Biophysical Research Communications, 2000
- Oxyradicals and DNA damageCarcinogenesis: Integrative Cancer Research, 2000
- Soybean Lipoxygenase-1 Oxidizes 3Z-NonenalPlant Physiology, 1998
- Dna Damage by Iron and Hydrogen Peroxide in Vitro and in VivoDrug Metabolism Reviews, 1998
- Lipid peroxidation as a potential endogenous source for the formation of exocyclic DNA adductsCarcinogenesis: Integrative Cancer Research, 1996
- Fatty Acid Substrate Specificities of Human Prostaglandin-endoperoxide H Synthase-1 and −2Journal of Biological Chemistry, 1995
- Detection of Endogenous Malondialdehyde-Deoxyguanosine Adducts in Human LiverScience, 1994
- Suggested mechanisms for the production of 4-hydroxy-2-nonenal from the autoxidation of polyunsaturated fatty acidsFree Radical Biology & Medicine, 1990