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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
Abstract 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.