DUAL EFFECTS OF FOLINIC ACID IN 5-FLUOROURACIL INDUCED KILLING OF HUMAN TUMOR-CELL LINES IN-VITRO

Folinic acid (leucovorin) is frequently used to augment and modulate t he clinical activity of 5-fluorouracil (5-FU) in patients with advance d gastrointestinal (Gl) cancer. However, there are conflicting opinion s concerning the optimal doses for these patients, and whether folinic acid modulates the clinical activity of 5-FU in patients with non-Gl cancer. To elucidate these questions, model experiments have been perf ormed on human tumor cell lines in vitro to determine the modulatory a ctivity of various concentrations of folinic acid on 5-FU mediated cyt otoxicity using a clonogenic assay. Three cell lines of colon cancer a nd 3 of glioblastoma origin were exposed to 5-FU alone or with folinic acid for 24 hours. It was observed that relatively low concentrations of folinic acid enhanced the cytotoxicity of 5-FU against the colon c ancer lines whereas higher concentrations were less effective. Folinic acid did not enhance the 5-FU mediated killing of the glioma cell lin es at any concentration (0.01-100 mu g/ml). On the contrary, folinic a cid seemed to counteract the cytotoxic effect of 5-FU in a reasonably dose-dependent fashion. These results may suggest that the value of fo linic acid in the treatment of non-Gl cancer with 5-FU should be evalu ated within the framework of controlled clinical trials, and that high doses of folinic acid may not necessarily be more effective than low.