Enzymic reduction of carcinogenic aromatic nitro compounds by rat and mouse liver fractions

Abstract

The enzymatic reduction of 2-nitroaphthalene and similar aromatic nitro compounds by rat liver extracts was investigated. The incubation of 2-nitronaphthalene with the post-mitochondrial fraction of rat and mouse liver led to the slow formation of 2-naphthylamine and to the disappearance of 2-nitronaphthalene; the reaction also occurred with the cytoplasmic and microsomal fractions of rat liver and was generally accelerated by NADPH and FMN. No 2-naphthylhydroxylamine could be observed at any time during the reduction, even using a gas-liquid chromatographic system capable of detecting 5 μg of 2-naphthylhydroxylamine added to the incubation mixture. The similar incubation of 4-nitrobiphenyl and 1-nitronaphthalene also led to the slow formation of the corresponding arylamine, with no evidence of hydroxylamine accumulation. 2-Naphthylamine was also produced both chemically and enzymatically by incubating 2-naphthylhydroxylamine with rat liver post-mitochondrial supernatant. In contrast to 2-nitronaphthalene, 4-nitroquinoline- N-oxide was rapidly reduced by rat liver post-mitochondrial fraction to yield high levels of the 4-hydroxylamine derivative, as well as small but significant quantities of the corresponding amine.