Human tissues degrade uridine much less than thymidine. Possible consequence for 5-fluorouracil therapy

In view of clinical trials to improve FUra chemotherapy of cancer by combined application with Urd and dThd, we investigated the capacity of human tissues to split these nucleosides. All human normal and neoplastic tissues gave a uridine-splitting activity which can be inhibited by beta-L-pTdR and behaves in this respect as uridine-deoxyuridine phosphorylase (EC 2.4.2.3). dThd splitting, however, which is 2-9-fold higher than that of Urd, is insensitive towards beta-L-pTdR, confirming earlier results that it is due to thymidine phosphorylase (EC 2.4.2.4). On the other hand, tissues, e.g., spleen of rats and mice, in which dThd and Urd are split by uridine-deoxyuridine phosphorylase, degrade 2-5-fold more Urd than dThd. Thus, free pyrimidine base competing with FUra for degradation and thus prolonging the life time of the drug in the body, will be formed mainly from dThd in the human body but more so from Urd in the rat or mouse.