INTERACTIVE EFFECTS OF NITRIC-OXIDE AND THE P53 TUMOR-SUPPRESSOR GENEIN CARCINOGENESIS AND TUMOR PROGRESSION

The tumor suppressor gene product p53 plays an important role in the c ellular response to DNA damage, DNA damage can lead to p53-mediated gr owth arrest and apoptosis, High concentrations of nitric oxide (NO) an d NO metabolites such as peroxynitrite and NO2 cause DNA damage and ha ve been shown to be mutagenic. Furthermore, NO induces p53 accumulatio n and, as part of a feedback loop, p53 mediates transcriptional transr epression of inducible nitric oxide synthase. Recent studies have show n increased expression and activity of nitric oxide synthase isoforms in human cancer. NO has both genotoxic and angiogenic properties, so t hat increased NO production may select mutant p53 cells and contribute to human carcinogenesis and tumor progression.