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  • Title: Effects of 5-fluorouracil derivative UFT on thymidylate synthetase and thymidine kinase in rat colorectal tumors.
    Author: Sakamoto S, Kawachi Y, Iwama T, Kuwa K, Suzuki T, Mitamura T, Kudo H, Sassa S, Yoshimura S, Maemura T, Nakayama T, Ohsawa M, Hara Y.
    Journal: Anticancer Res; 1999; 19(1A):245-50. PubMed ID: 10226549.
    Abstract:
    BACKGROUND: Thymidylate synthetase and thymidine kinase are key enzymes involved in de novo and salvage pathways for pyrimidine nucleotide synthesis, respectively. MATERIALS AND METHODS: Weekly injections of 1,2-dimethyl-hydrazine induced high incidence of colorectal adenocarcinomas in rats. RESULTS: An increased activity of thymidylate synthetase was found in the poorly differentiated adenocarcinomas of the chemically induced rat colorectal tumors. Six-week oral administration of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil (UFT) reduced the total number of colorectal tumors, with the reduction of thymidylate synthetase activity in the poorly-differentiated type, though the mRNA expression of thymidylate synthetase and thymidine kinase differed little between the groups with or without UFT treatment. CONCLUSIONS: These results indicate that the long-term oral administration using UFT suppresses colorectal carcinogenesis and the growth of the poorly-differentiated type tumors.
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