Upregulation of Enzymes Metabolizing 5-Fluorouracil in Colorectal Cancer

BACKGROUND: The purpose of this study was to compare the activities of various enzymes, participating in the metabolism of 5-fluorouracil, between colorectal cancer and nontumor tissues and to investigate the association of the enzyme activities with clinicopathological backgrounds. METHODS: Activities of seven enzymes involved in nucleic acid metabolism--orotate phosphoribosyltransferase (OPRT), ribonucleotide reductase (RNR), thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, uridine phosphorylase and thymidine kinase (TK)--were measured in tumor and nontumor tissues from 28 patients who were operated on for colorectal cancers. RESULTS: OPRT, thymidylate synthase, RNR, thymidine phosphorylase, uridine phosphorylase and thymidine kinase activities were significantly higher in tumor areas than in nontumor areas. OPRT showed the highest T/N ratio (the ratio of each enzyme activity in tumor areas to that in nontumor areas). The T/N ratio of RNR activity showed a tendency to be associated with lymph node metastasis and Dukes classification. CONCLUSION: The results suggest that OPRT is a main enzyme participating in the phosphorylation of 5-fluorouracil and has an important role in tumor growth. The T/N ratio of RNR may be predictive of tumor progression.