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.6’7 KeywordsThymidine KinaseColon AdenocarcinomaHuman Colon AdenocarcinomaHuman Colon Cancer Cell LineThymidylate SynthetaseThese 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.