Regulation of Thymidylate Synthase in Human Colon Cancer Cells Treated with 5-Fluorouracil and Interferon-Gamma

  • Edward Chu
  • Carmen J. Allegra
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 339)


5-Fluorouracil (5-FU) remains, at present, the single most active agent for the treatment of human colorectal cancer. When used as a single agent against advanced disease, it is associated with an overall response rate of only 15–20%, and therapy with 5-FU is unable to prolong the survival of treated patients [1–3]. Since few other agents have been identified for the treatment of human colorectal cancer, considerable attention has focused on elucidating the basic mechanisms of 5-FU action. The cytotoxic effects of 5-FU have been traditionally ascribed either to inhibition of the critical target enzyme thymidylate synthase (TS) by the 5-FU metabolite 5-fluoro-2′-deoxyuridine-5′-monophosphate (FdUMP) with subsequent inhibition of thymidylate and DNA biosynthesis, to incorporation of the 5-FU metabolite 5-fluorouridine-5′-triphosphate (FUTP) into RNA with resultant inhibition of RNA synthesis and function, or to incorporation of the 5-FU metabolite 5-fluoro-2′-deoxyuridine-5′-triphosphate (FdUTP) into DNA with resultant inhibition of DNA synthesis and function [1–11]. The relative contribution of each of these metabolic processes remains unclear at this time.


H630 Cell Human Colorectal Cancer Dialyze Fetal Bovine Serum Fluorinated Pyrimidine Human Ovarian Cancer Line 
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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Edward Chu
    • 1
  • Carmen J. Allegra
    • 1
  1. 1.NCI-Navy Medical Oncology BranchNational Cancer Institute,NIHNMOB 8/5101-Naval HospitalBethesdaUSA

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