Genotoxicity of nitric oxide produced from sodium nitroprusside

Induction of mutation and micronucleus (MN) formation by nitric oxide (NO) was investigated in mammalian cells using sodium nitroprusside (SNP) as a drug donor of NO. Results showed that the concentration of NO2- in the tested solution rose according to time- and concentration-exposure to SNP. The treatment of SNP (0.5-8 micromol/ml with S9 or 2-8 micromol/ml without S9) induced a concentration-dependent increase in the mutation frequency at the gpt gene locus in g12 cells and caused a 13- (-S9) to 25- (+S9) fold increase above the background level at the highest concentration. A statistically significant increase in the number of micronucleated binucleated cells (MNBN) was also observed in treated groups. MNBN per thousand, MN per thousand and the proportion of the multiple micronuleated cells increased in a concentration-dependent manner in the concentration range of SNP (0.5-4 micromol/ml with S9 or 2-8 micromol/ml without S9). Our results indicate that SNP, an NO releasing drug, is genotoxic in g12 cells.