Metabolism of fluoropyrimidines in cancer patients (Part II).

概要

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Following studies on the fluoropyrimidine metabolism in patients with advancedgastric cancer, which showed increased activities of both uridine and thymidinephosphorylase in gastric cancer tissues, we examined in this study uridine andthymidine kinase, and orotate phosphoribosyltransferase, all of which were concernedin the further activation of fluoropyrimidines. Moreover, dihydrouracil dehydrogenaseactivity, a rate-lemiting factor of fluorouracil degradation, was also determined invarious tissues. As a result, it was demonstrated that kinases are more active in cancertissues than in those of other normal organs. On the other hand, dihydrouracildehydrogenase activity was not changed in cancer or noncancer tissues, except for agreater increase (7-fold) in the liver. It was also noted that the dihydrouracildehydrogenase activity was inhibited by uracil, resulting an elevated concentration offluorouracil in the tissues as described previously.<BR>Thus, it is suggested that fluoropyrimidines essentially have tumor-selective toxicityin patients with gastric cancer, and uracil coadministration would enhance the activityof fluoropyrimidines.