Publication Date:
2001-06-16
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, S H -- Oe, T -- Blair, I A -- CA16520/CA/NCI NIH HHS/ -- CA65878/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2001 Jun 15;292(5524):2083-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Cancer Pharmacology, University of Pennsylvania, 1254 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11408659" target="_blank"〉PubMed〈/a〉
Keywords:
Aldehydes/chemistry/metabolism
;
Antioxidants/chemistry
;
Ascorbic Acid/adverse effects/chemistry/metabolism/*pharmacology
;
Buffers
;
Copper/pharmacology
;
Cyclooxygenase 1
;
Cyclooxygenase 2
;
DNA Adducts/chemistry/metabolism
;
DNA Damage
;
Epoxy Compounds/chemistry/metabolism
;
Ferrous Compounds/pharmacology
;
Humans
;
Isoenzymes/metabolism
;
Linoleic Acids/*chemistry/metabolism
;
Lipid Peroxides/*chemistry/metabolism
;
Membrane Proteins
;
Metals/pharmacology
;
Mutagens/*chemistry/metabolism
;
Oxidants/adverse effects/chemistry/metabolism/pharmacology
;
Oxidation-Reduction
;
Prostaglandin-Endoperoxide Synthases/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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