Given that wild-type P53 negatively regulates NOS2 [18], and the oncogenic actions of mutant P53 are comparable to mechanisms of NOS2 identified during breast cancer disease progression [7,8,9,12,19,20], this study investigates potential NO-induced P53 mutations and subsequent transcriptional and phenotypic changes associated with chronic exposure of breast epithelial cells to the exogenous NO donor DETANO. The gene discussed is NOS2; the disease is breast cancer.