The role of nitric oxide (NO.) in the carcinogenic process.

The inflammatory process has long been known to be a risk factor for human cancers, particularly of the lung, bladder, colon, stomach, and female breast. Earlier hypothesis cited production of oxygen radicals, release of cytokines, and synthesis of prostaglandins and leukotrienes as biochemical modulators of the carcinogenic process. The discovery of NO. as a product of cells in the immune system has implicated this chemical in the mechanism of carcinogenesis, particularly when NO. is overproduced over a long period of time. After briefly reviewing the important chemical reactions of NO. under physiological conditions, we examine how the chemistry of its key reactants toward biologically important molecules relate to DNA damage and cytotoxicity. In these two processes, NO may play an important role in currently accepted models of multistage carcinogenesis.