Cytotoxic effect of sodium nitroprusside on PC12 cells

To investigate the biochemical mechanism responsible for NO-induced neurotoxicity, the effect of sodium nitroprusside(SNP), a NO-generating agent, on PC12 cells was studied. The cell density was dose-dependently inhibited by SNP. Neuronally differentiated PC12 cells showed a higher resistance to SNP than the undifferentiated cells. The inhibitory effect was enhanced by 8-Br-cGMP, and reduced by methylene blue. However, 8-Br-cGMP alone had no significant cytotoxicity. SNP also inhibited [3H]-thymidine incorporation into the cells in a dose-dependent manner. The dose response curves for reducing cell density and for inhibiting thymidine incorporation; were found to be virtually superimposable. These results suggested that cytotoxieity elicited by NO seemed to be due to inhibition of DNA synthesis in PC12 cells.