[Innate resistance to thymidylate synthase inhibition after 5-fluorouracil treatment--a rationale of combined use of cisplatin and its optimal administration dose].
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.
Omura
K
K
Dept. of Surgery 1, Kanazawa University School of Medicine.
Hashimoto
T
T
Kawakami
K
K
Kanehira
E
E
Watanabe
T
T
Hirano
K
K
Watanabe
S
S
Watanabe
Y
Y
Shirasaka
T
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051381:Rats; D012517:Sarcoma, Yoshida / Q000188:drug therapy / Q000201:enzymology*; D005641:Tegafur / Q000008:administration & dosage / Q000494:pharmacology; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014498:Uracil / Q000008:administration & dosage / Q000494:pharmacology
D005641:Tegafur; D014498:Uracil; D013940:Thymidylate Synthase; D002945:Cisplatin; D005472:Fluorouracil