Enhancement of fluorinated pyrimidine‐induced cytotoxicity by leucovorin in human lung cancer cell lines

Reduced folates have been shown to increase the cytotoxicity of 5‐fluorouracil (FUra) by stabilizing the fluorodeoxyuridine monophosphate: thymidylate synthase complex, thus increasing the block in the DNA synthetic pathway. Using an in vitro tetrazolium colorimetric (MTT) cytotoxic assay, we tested the effects of FUra and 5‐fluorodeoxyuridine (FUdR) with and without leucovorin (LV) on a panel of 7 human lung cancer cell lines. LV at a concentration of 20 μM enhanced the cytotoxicity of FUra and of FUdR in all of the cell lines. Quantitatively, LV had a higher degree of enhancement on FUdR than on FUra cytotoxicity in 6 cell lines. There was equivalent enhancement in the only remaining line. The differential effects of LV on the cytotoxicity of FUra vs. FUdR in these lung carcinoma lines contrasts with a quantitatively similar enhancement of cytotoxicity between FUra and FUdR in colon cancer lines previously reported from our laboratory. This suggests that the metabolism of FUra may be different in these lung cancer cell lines.