Predictive model of the regulation of TS status
by balancing the
accumulation of the inactive FdUMP-TS form and the storage of the
active free-TS form in the 5-FU-resistant HCT116RF10 cells
and parental HCT116 cells. We show that the trapping of FdUMP by TS
enzyme is more effective in 5-FU-resistant HCT116RF10 cells
than in parental HCT116 cells. In addition, we predict that the regulation
of the balance between the storage of the active TS form and the accumulation
of FdUMP-TS is responsible for direct resistance to 5-FU. 5-FU, 5-fluorouracil;
FUdR, 5-fluorodeoxyuridine; FdUMP, 5-fluorodeoxyuridine monophosphate;
TS, thymidylate synthase.