Incubation in vitro of recombinant wild-type murine p53 protein with S-nitroso-N-acetyl-dl-penicillamine [a nitric oxide (NO)-releasing compound] has resulted in a change of p53 conformation and also in a significant decrease of its specific DNA binding activity. Similarly, upon treatment with S-nitroso-N-acetyl-dl-penicillamine (2–5 mm) or S-nitrosoglutathione (1–2 mm), human breast cancer cells (MCF-7), which express wild-type p53, rapidly accumulated p53 protein in the nuclei. This p53 protein, however, possessed a significantly decreased activity of specific DNA binding. On the other hand, lower concentrations of NO donors (0.25–0.5 mm) stimulated p53 accumulation as well as its DNA binding activity. These results suggest that excess NO produced in inflamed tissues could play a role in carcinogenesis by impairing the tumor suppressor function of p53.