Comparative reduction of 1-nitro-3-nitrosopyrene and 1-nitro-6-nitrosopyrene: implications for the tumorigenicity of dinitropyrenes.
Dinitropyrenes are mutagenic environmental pollutants. Of these compounds, 1,6-dinitropyrene is a potent tumorigen while 1,3-dinitropyrene appears to be weakly or non-tumorigenic. Two-electron reduction of dinitropyrenes yields nitro-nitrosopyrenes, which have been shown previously to be the major aerobic metabolites of these compounds in vitro. Further reduction of nitrosopyrenes is required for their activation to a DNA-reactive N-hydroxylamines. In this work, 1-nitro-3-nitrosopyrene was synthesized and the electrochemical and enzyme-catalyzed reduction of 1-nitro-3-nitrosopyrene has been compared with that of 1-nitro-6-nitrosopyrene. As determined by cyclic voltammetry, the reduction potentials of 1-nitro-3-nitrosopyrene, 1-nitro-6-nitrosopyrene and their parent dinitropyrenes were similar, although 1-nitro-3-nitrosopyrene did have a slightly more negative cathodic peak potential than the other three compounds. The NADPH-mediated reduction of 1-nitro-6-nitrosopyrene to intermediates which reduce succinoylated cytochrome c was faster than that of 1-nitro-3-nitrosopyrene. In the presence of rat liver microsomes or cytosol, the reduction of 1-nitro-6-nitrosopyrene was faster than that of 1-nitro-3-nitrosopyrene. These differences in the rates of nitro-nitrosopyrene reduction may be one factor contributing to the lower tumorigenic potential of 1,3-dinitropyrene relative to 1,6-dinitropyrene.
Djuric
Z
Z
Department of Internal Medicine, Wayne State University, Detroit, MI 48201.
D000818:Animals; D002273:Carcinogens / Q000737:chemistry* / Q000633:toxicity; D004563:Electrochemistry; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009603:Nitroso Compounds / Q000737:chemistry* / Q000633:toxicity; D010084:Oxidation-Reduction; D011721:Pyrenes / Q000737:chemistry* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D009603:Nitroso Compounds; D011721:Pyrenes; C047860:1-nitro-6-nitrosopyrene; C076369:1-nitro-3-nitrosopyrene