Comparison between short or long exposure to 5-fluorouracil in human gastric and colon cancer cell lines: biochemical mechanism of resistance.

摘要: Recent preclinical and clinical data indicate that the main mechanisms of 5-fluorouracil (5-FU) cytotoxicity depend on mode administration. To gather further insight into major causes acquired 5-FU resistance, drug-sensitive human gastric (M2), colon (HT29) breast (MCF7) cancer cell lines were repeatedly exposed to a fixed concentration given either for 1 or 24 h. Although equieffective doses (IC50) used, resistance h exposure developed faster in all models than exposure. Cell with application only partly cross-resistant exposure, whereas protracted displayed significant cross-resistance schedule. Resistance methotrexate was seen 5-FU. All 5-FU-resistant showed reduced incorporation cellular RNA. Furthermore, elevations thymidylate synthase but also one line bolus No alterations folylpolyglutamate resistant lines. These support concept application. Incorporation fluorouridine triphosphate RNA appears be most important mechanism action schedules, inhibition becomes more as infusion time is prolonged. could have implications interaction at different schedules various other cytostatic agents.