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Enhancement of Xanthine Dehydrogenase Mediated Mitomycin C Metabolism by Dicumarol¹

Department of Nutrition and Cellular and Molecular Pharmacology and Physiology Program, University of Nevada, Reno, Nevada 89557-0132

² To whom requests for reprints should be addressed.

These studies examined the effect of dicumarol on xanthine dehydrogenase (XDH), an enzyme recently shown to bioreduce mitomycin C. Dicumarol, which has previously been shown to inhibit xanthine oxidase (XO), inhibited both XDH and XO mediated conversion of xanthine to uric acid but potentiated the metabolism of mitomycin C by XDH and XO. Formation of 2,7-diaminomitosene following mitomycin C bioactivation by XDH was increased 3-fold aerobically and 4-fold hypoxically when 20 µM dicumarol was included in the reaction mixture. XO mediated metabolism of mitomycin C hypoxically was increased approximately 50% by the inclusion of dicumarol.

¹ This work was supported by USPHS Grant CA-43660 from the National Cancer Institute and by the Reno Cancer Center.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 9/ 8/92. Accepted 10/26/92.

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