It has been suggested that the carcinogenicity of asbestos may be due to production of peroxynitrite. This potent oxidant is formed from the reaction between superoxide and nitric oxide and is very reactive, with a half-life of approximately 1 second under physiological conditions. Upon endocytosis into A549 cells, nitric oxide is known to be formed from the induction of the inducible form of nitric oxide synthase and superoxide is produced from the redox cycling of the iron mobilized from the surface of the asbestos fiber. Peroxynitrite production is therefore a likely occurrence in this case and may lead to oxidation of DNA, which can cause mutations and, subsequently, tumor formation.;The objective of this research was to determine whether peroxynitrite was capable of oxidizing DNA in human lung epithelial (A549) cells. The results combined to suggest that peroxynitrite did oxidize DNA in A549 cells and this oxidation was rapidly repaired. |