ROLE OF NITRIC-OXIDE IN GENOTOXICITY - IMPLICATION FOR CARCINOGENESIS

Reactive oxygen species can initiate carcinogenesis by virtue of their capacity to react with DNA and cause mutations. Recently, it has been suggested that nitric oxide (NO) and its derivatives produced in infl amed tissues could contribute to the carcinogenesis process. Genotoxic ity of NO follows its reaction with oxygen and superoxide. It can be d ue either to direct DNA damage or indirect DNA damage. Direct damage i ncludes DNA base deamination, peroxynitrite-induced adducts formation and single strand breaks in the DNA. Indirect damage is due to the int eraction of NO reactive species with other molecules such as amines, t hiols and lipids. The efficiency of one pathway or another might depen d on the cellular antioxidant status or the presence of free metals.