Mutagenesis induced by the nitric oxide donor sodium nitroprusside in mouse cells.
Nitric oxide (NO) is an important bioactive molecule derived from endogenous or exogenous sources. NO can exhibit genotoxicity through the formation of reactive nitrogen species. Nitric oxide releasing compounds, such as sodium nitroprusside, are widely used for the therapy of hypertension and other disorders. Here we have characterized the mutagenicity of sodium nitroprusside in mouse embryo fibroblasts carrying the cII mutation reporter gene. Sodium nitroprusside dose-dependently increased the cII mutant frequency to levels approximately 5-fold above background. The mutational spectrum induced by sodium nitroprusside was characterized by an increase in the fraction of G-->T transversion mutations (P < 0.003) but the proportion of transition mutations was not increased. We discuss the potential origin of the G-->T mutations induced by this compound in mammalian cells.
Lee
Dong-Hyun
DH
Division of Biology, Beckman Research Institute of the City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
Pfeifer
Gerd P
GP
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000187:drug effects*; D020030:Nitric Oxide Donors / Q000633:toxicity*; D009573:Nitrites / Q000378:metabolism; D009599:Nitroprusside / Q000633:toxicity*; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics; D019076:Transgenes / Q000187:drug effects; D014764:Viral Proteins / Q000187:drug effects / Q000235:genetics
D020030:Nitric Oxide Donors; D009573:Nitrites; D014157:Transcription Factors; D014764:Viral Proteins; C039000:cII protein, bacteriophage lambda; D009599:Nitroprusside