Detection of a Reactive Metabolite of Misonidazole in Hypoxic Mammalian Cells

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Abstract
A misonidazole metabolite capable of reacting with guanosine was detected in extracts of Chinese hamster ovary cells exposed to misonidazole under hypoxic conditions. A misonidazole metabolite with identical chromatographic properties and reactivity with guanosine was detected in earlier studies with misonidazole reduced to the hydroxylamine state by chemical, radiolytic or electrolytic means. The proposed structure of the guanosine product involves the addition of a 2-carbon fragment between the N1 and N2 positons of guanosine. Rearrangement of the N-hydroxy derivative of misonidazole to a C-hydroxy derivative is postulated as the initial step in the reaction scheme. [The use of misonidazole as a radiosensitizer in the treatment of human tumors is discussed.].