Kinetic analysis of 5-fluorouracil action against various cancer cells

Abstract

Based on our recent kinetic analysis, which made it possible to distinguish between the cell-killing actions of cell cycle phase-specific and non-specific agents, we attempted to elucidate the actions of 5-fluorouracil (FUra) on three different cancer cell lines. By colony-forming assay, the concentrations of fluorouridine (FUrd), fluorodeoxyuridine (FdUrd) or FUra giving 90% cell kill (IC90) at various exposure times (texps) were obtained. With P388 cells, the curve of texps-IC90 for FUrd on a log-log scale was linear with a slope of -1, which is typical for cell cycle phase-nonspecific agents. In contrast, the curve for FdUrd showed a much steeper slope than -1, which is characteristic for cell cycle phase-specific agents. We found that the curve for FUra was exactly the same as that for FUrd, indicating that the mode of FUra action on P388 leukemia is analogous to that of FUrd. Similar results were observed with human colon and renal cancer cell lines, HT-29 and KU-2, although when the cells were exposed to relatively low concentrations of FUra for a long time, a cell cycle phase-specific action became evident.