Cytotoxic versus genotoxic effects of nitric oxide (NO)

Toxicol Lett. 1999 May 20;106(1):59-67. doi: 10.1016/s0378-4274(99)00019-3.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects
  • DNA Damage
  • Dose-Response Relationship, Drug
  • Mice
  • Micronucleus Tests
  • Molsidomine / analogs & derivatives
  • Molsidomine / toxicity
  • Mutagens / toxicity*
  • Nitric Oxide / toxicity*
  • Tumor Cells, Cultured

Substances

  • Mutagens
  • Nitric Oxide
  • linsidomine
  • Molsidomine