A constellation of reactive electrophiles and free radicals capable of damaging cellular constituents is generated during normal physiological and pathophysiological processes. It is well documented that reactive species of oxygen have a high capacity to react with DNA and can cause mutations in genomic DNA and so potentially initiate carcinogenesis. Recently, it has been shown that nitric oxide (NO) and its reactive derivatives produced in inflamed tissues could also contribute to the carcinogenic process. Nitrogen oxides generated by the oxidation of NO with oxygen or superoxide, act as genotoxic agents via direct damage or indirect damage mechanisms. Direct damage of reactive nitrogen oxides includes DNA base deamination, adduct formation on DNA and DNA strand breaks. However, indirect damage of DNA is due to the interaction of reactive nitrogen oxides with other molecules that may result in increased secondary radical generation, alteration in the regulation of gene expression and signal transduction.