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Science 15 June 2001:
Vol. 292. no. 5524, pp. 2083 - 2086
DOI: 10.1126/science.1059501
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Reports

Vitamin C-Induced Decomposition of Lipid Hydroperoxides to Endogenous Genotoxins

Seon Hwa Lee, Tomoyuki Oe, Ian A. Blair*

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.

Center for Cancer Pharmacology, University of Pennsylvania, 1254 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USA.
*   To whom correspondence should be addressed. E-mail: ian{at}spirit.gcrc.upenn.edu

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N-Acetylcysteine and Celecoxib Lessen Cadmium Cytotoxicity Which Is Associated with Cyclooxygenase-2 Up-regulation in Mouse Neuronal Cells.
M. E. Figueiredo-Pereira, Z. Li, M. Jansen, and P. Rockwell (2002)
J. Biol. Chem. 277, 25283-25289
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Vitamin C Prevents DNA Mutation Induced by Oxidative Stress.
E. A. Lutsenko, J. M. Carcamo, and D. W. Golde (2002)
J. Biol. Chem. 277, 16895-16899
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2001 W.O. Atwater Memorial Lecture and the 2001 ASNS President's Lecture: Human Nutrient Requirements: The Challenge of the Post-Genome Era.
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J. Nutr. 132, 621-629
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Science. ISSN 0036-8075 (print), 1095-9203 (online)