Flow cytometric analysis of cell-killing actions of 5-fluorouracil in human colorectal cancer cells.

To confirm our previous kinetic analysis of the mode of cell-killing action of 5-fluorouracil (5-FU), we carried out a flow cytometric analysis with human colorectal cancer DLD-1 cells. Cells were treated with each cytotoxic concentration of 5-FU for 1 or 72 h, and the periodic changes in flow cytometric pattern were compared with those of 5-fluorouridine (FUrd) and 5-fluoro-2'-deoxyuridine (FdUrd). When cells were cultured with 5-FU for 72 h, most of them accumulated in S phase and remained there. This pattern was the same as that seen in cells that were continuously exposed to FdUrd. In contrast, when cells were exposed to 5-FU for 1 h and cultured in drug-free medium, they ended the cell-cycle traverse in either G2/M or G1 phase after an immediate but transient accumulation in S phase. Results were identical to those observed with cells similarly treated with FUrd. These results demonstrated a good accordance with those of our kinetic analysis, and strongly suggested that the mode of cell-killing exhibited by 5-FU differs with exposure time: 5-FU acts like FUrd in short exposure conditions, and it acts similarly to FdUrd in continuous exposure conditions.