Metabolism of 1-nitropyrene and formation of DNA adducts in Salmonella typhimurium

Abstract

1-Nitropyrene is slowly reduced by intact cells of Salmonella typhimurium to yield 1-aminopyrene and N-acetyl-1-aminopyrene plus six unidentified minor products. When the bacteria are exposed to tritiated 1-nitropyrene, increasing amounts of radioactivity become bound to DNA as the nitropyrene is metabolized. Enzymatic hydrolysis of the labelled DNA yields low molecular weight labelled compounds which probably represent nucleoside adducts formed by the reaction of nitropyrene metabolites with DNA. Results with appropriate mutant strains indicate that bacterial nitroreductases are involved in activating nitropyrene to a reactive intermediate that binds to DNA and that nitropyrene adducts in DNA are subject to excision repair.