Irreversible Inhibition of Dehalogenation of 5-Iodouracil by 5-Diazouracil and Reversible Inhibition by 5-Cyanouracil

The dehalogenation of 5-iodouracil was studied in vitro, and two inhibitors of the reaction were found. One of these, 5-cyanouracil, previously reported to inhibit dihydrouracil dehydrogenase, was shown in this study to inhibit dehalogenation. The second inhibitor, 5-diazouracil, was shown to be an irreversible inhibitor of dehalogenation, which appears to act at the substrate binding site. Diazouracil was shown to be an effective inhibitor in vivo and may be of value in enhancing tumor therapy, including radiosensitization, with halogenated pyrimidines.