Cytotoxic versus genotoxic effects of nitric oxide (NO)

The pathobiochemistry of endogenous reactive nitrogen species includes functions in inflammation and carcinogenesis. Genotoxicity has been suggested to play a major role. Two donor compounds, spermine NONOate, which can release authentic nitric oxide (NO), and 3-Morpholino-sydnonimine hydrochloride (SIN-1), which generates NO together with superoxide, possibly yielding peroxynitrite (ONOO-), were investigated in L5178Y mouse lymphoma cells for cytotoxic and genotoxic effects. As demonstrated by cell growth, 'micronucleus' and 'comet' assays NO, with and without concomitant superoxide formation, did not induce significant genotoxicity at concentrations with low cytotoxicity. Therefore, at least for the three tested parameters and the chosen time window, the pronounced cytotoxicity exhibited by NO and its oxidative metabolites most likely outweighs any genotoxic potential.