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Schedule dependent inhibition of thymidylate synthase and tumor growth by 5‐fluorouracil in yoshida sarcoma bearing rats
Author(s) -
Tsujinaka Md Toshimasa,
Kido Yoshihiro,
Shiozaki Hitoshi,
Mori Takesada,
Karakousis Constantine P.
Publication year - 1992
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.2930500313
Subject(s) - thymidylate synthase , fluorouracil , medicine , schedule , sarcoma , cancer research , oncology , growth inhibition , chemotherapy , pharmacology , biochemistry , cell growth , pathology , biology , computer science , operating system
Schedule dependent inhibition of thymidylate synthase (TS) and tumor growth by 5‐fluorouracil (FUra) was examined in Yoshida sarcoma (YS) bearing Donryu rats. After implantation of YS cells (1 × 10 4 ), FUra (20 mg/kg/day) was continuously (group C) or daily bolus injection (group B) administered for 6 days. On day 7, tumor weight was 1.57 ± 0.58 g in group C and 0.45 ± 0.10 g in group B ( P < 0.01), free TS was 2.23 ± 83 fmol/mg protein in group B and 96 ± 55 fmol/mg protein in group C ( P < 0.05), and inhibition rate of TS was 88.3 ± 5.3% in group C and 94.7 ± 3.0% in group B ( P < 0.05). A significant correlationship was found between free TS and tumor weight ( P < 0.05). As the next step, continuous infusion (group C) or daily bolus injection (group B) for 6 days was started on day 5 after implantation of YS cells. The relative increase of tumor on day 9 was 256 ± 111% in group C and 112 ± 22.1% in group B ( P < 0.05). On day 11, total TS of the resected tumor was 650 ± 153 fmol/mg protein in group C and 391 ± 124 fmol/mg protein in group B ( P < 0.05), and inhibition rate of TS was 78.8 ± 12.4% in group C and 84.4 ± 8.6% in group B. Daily bolus injection of FUra causes a superior antitumor and antimetabolic effect. The schedule dependent cytotoxicity of FUra should be taken into account when a chemotherapeutic protocol is designed. © 1992 Wiley‐Liss, Inc.