Cytotoxic versus genotoxic effects of nitric oxide (NO)

The pathobiochemistry of endogenous reactive nitrogen species includes func tions in inflammation and carcinogenesis. Genotoxicity has been suggested t o play a major role. Two donor compounds, spermine NONOate, which can relea se authentic nitric oxide (NO), and 3-Morpholino-sydnonimine hydrochloride (SIN-I), which generates NO together with superoxide, possibly yielding per oxynitrite (ONOO-), were investigated in L5178Y mouse lymphoma cells for cy totoxic and genotoxic effects. As demonstrated by cell growth, 'micronucleu s' and 'comet' assays NO, with and without concomitant superoxide formation , did not induce significant genotoxicity at concentrations with low cytoto xicity. 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. (C) 1999 Elsevie r Science Ireland Ltd. All rights reserved.