Reaction of 2-nitroimidazole metabolites with guanine and possible biological consequences

Nitroimidazoles, under hypoxic conditions, undergo reduction reactions producing a variety of reactive species; at the same time, they exert a variety of biological effects. The purpose of the present study was to investigate the reduction chemistry of 2-nitroimidazoles, the reaction of the reduced metabolites with nucleic acid constituents and the possible biological significance of these reactions. Earlier studies had demonstrated that, following reduction, 2-nitroimidazoles react with guanine derivatives to produce identical to that seen on reaction of glyoxal with the same guanine derivatives. We report here the identification of this product in the nucleic acid of cells exposed to 2-nitroimidazoles under hypoxic conditions. Using glyoxal as a model compound, we also demonstrate that cellular formation of such a product could account for a number of the biological properties of 2-nitroimidazoles under hypoxic conditions.