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  • Title: [Innate resistance to thymidylate synthase inhibition after 5-fluorouracil treatment--a rationale of combined use of cisplatin and its optimal administration dose].
    Author: Omura K, Hashimoto T, Kawakami K, Kanehira E, Watanabe T, Hirano K, Watanabe S, Watanabe Y, Shirasaka T.
    Journal: Gan To Kagaku Ryoho; 1994 Sep; 21(12):2007-11. PubMed ID: 8085851.
    Abstract:
    We examined the changes of the number of FdU MP binding sites of thymidylate thynthase (TS-BS) in Yoshida sarcoma after administration of 5-FU to the tumor bearing rats. We also investigated the optimal dose of CDDP for the increase of intracellular folate level. In the group received consecutive 7-days administration of UFT (U-7 group), total TS-BS was significantly increased compared with non-treatment group and the group received only UFT (U-1 group). For free TS-BS, however, there was no difference despite of UFT administration. Thymidylate synthase inhibition rate (TSIR) was, therefore, significantly high in U-7 group compared with U-1 group. It seemed necessary to take some counter measure for the induction of TS in the tumor tissue when 5-FU chemotherapy was performed. The optimal dose of CDDP as a modulator of 5-FU was 1 mg/kg in rat when it was estimated from the changes of intracellular folate levels after administration, which was less than the dose to reveal its own anticancer effect.
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