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The FASEB Journal, Vol 11, 443-448, Copyright © 1997 by The Federation of American Societies for Experimental Biology
REVIEWS |
S Ambs, SP Hussain and CC Harris
Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-4255, USA.
The tumor suppressor gene product p53 plays an important role in the cellular response to DNA damage. DNA damage can lead to p53-mediated growth arrest and apoptosis. High concentrations of nitric oxide (NO) and NO metabolites such as peroxynitrite and NO2 cause DNA damage and have been shown to be mutagenic. Furthermore, NO induces p53 accumulation and, as part of a feedback loop, p53 mediates transcriptional transrepression of inducible nitric oxide synthase. Recent studies have shown increased expression and activity of nitric oxide synthase isoforms in human cancer. NO has both genotoxic and angiogenic properties, so that increased NO production may select mutant p53 cells and contribute to human carcinogenesis and tumor progression.
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