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Departments of Microbiology [S. G.] and Biochemistry [G. M. C., S. G.] and Program in Cellular and Molecular Biology [G. M. C., S. G.], University of Miami, Coral Gables, Florida 33146
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.
1 This study was aided by funds from the American Cancer Society (Florida Division) and from Grant IN-51 I from the American Cancer Society, Inc.
2 Predoctoral trainee supported by USPHS Training Grant HE-05463 from the National Heart and Lung Institute.
Received 3/18/70. Accepted 9/ 2/70.
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