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 (S NP) as a drug donor of NO. Results showed that the concentration of NO ; in the tested solution rose according to time- and concentration-exp osure to SNP. The treatment of SNP (0.5-8 mu mol/ml with S9 or 2-8 mu mol/ml without S9) induced a concentration-dependent increase in the m utation 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 hig hest concentration. A statistically significant increase in the number of micronucleated binucleated cells (MNBN) was also observed in treat ed groups. MNBN parts per thousand, MN parts per thousand and the prop ortion of the multiple micronuleated cells increased in a concentratio n-dependent manner in the concentration range of SNP (0.5-4 mu mol/ml with S9 or 2-8 mu mol/ml without S9). Our results indicate that SNP, a n NO releasing drug, is genotoxic in g12 cells. (C) 1998 Elsevier Scie nce B.V.