Binding of nitroreduction products of misonidazole to nucleic acids and protein.

[14C]Misonidazole was reduced with zinc dust in aqueous solution in the presence of ammonium chloride. When the reduction mixture was allowed to react with calf thymus DNA and the reaction mixture was dialyzed, radioactivity was detected in the DNA fraction. Bovine albumin, after reaction with the reduction mixture and subsequent Bio-Gel P-2 column chromatography, was also found to be radioactive. The hydroxylamine derivative of misonidazole was detected in the reduction mixture. It is postulated that binding of nitroreduction products of misonidazole to cellular macromolecules is a probable mechanism for the cytotoxicity of misonidazole.