To aid in the clinical evaluation of zebularine, a potential oral antitumor agent, we initiated studies on the metabolism of zebularine in liver cytosol from humans and other mammals. Metabolism by aldehyde oxidase (AO, EC 1.2. 3.1) was the major catabolic route, yielding uridine as the primary metabolite, which was metabolized further to uracil by uridine phosphorylase. The inhibition of zebularine metabolism was studied using raloxifene, a ...