Enhanced Cytotoxicity of 5-Fluorouracil Combined with [6RS]Leucovorin and Recombinant Human Interferon-α2a in Colon Carcinoma Cells

  • Janet A. Houghton
  • David A. Adkins
  • Peter J. Houghton
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 339)


We had proposed previously that one mechanism of intrinsic resistance to 5-fluorouracil (FUra) in colon adenocarcinomas was suboptimal concentrations of intracellular 5,10-methylenetetrahydrofolate (CH2-H4PteGlun).1 Whereas the concentration of this reduced folate may not be rate limiting for thymidylate synthesis de novo, it may be suboptimal to allow maximal interaction between the FUra metabolite, 5-fluorodeoxyuridylate (FdUMP), and thymidylate synthase.1–5 Supplementation with a reduced folate, therefore, elevates intracellular levels of CH2-H4PteGlun and enhances the rate of formation or stabilization of the ternary complex. In human colon tumor xenografts, pools of CH2-H4PteGlun and H4PteGlun expanded by 2- to 5-fold in response to 24 hr infusions of [6RS]leucovorin ([6RS]LV), elevating species containing from 2 to 5 glutamate residues.67


Thymidine Kinase Colon Adenocarcinoma Human Colon Adenocarcinoma Human Colon Cancer Cell Line Thymidylate Synthetase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Janet A. Houghton
    • 1
  • David A. Adkins
    • 1
  • Peter J. Houghton
    • 1
  1. 1.Department of Biochemical and Clinical PharmacologySt. Jude Children’s Research HospitalMemphisUSA

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