Failure of 5-fluorouracil and methotrexate to destroy the reproductive integrity of a human breast cancer cell line (MCF-7) growing in vitro

Human breast cancer cell (MCF-7) in continuous culture were exposed to clinically achievable extra-cellular concentrations of methotrexate and 5-fluorouracil. A 24-hr treatment with 5-fluorouracil (up to 7.7 × 10^-6 M) or methotrexate (up to 10^-5 M) failed to reduce the colony-forming ability of MCF-7 cells, although marked dose-dependent effects on the incorporation of [³H]-deoxyuridine into DNA were observed immediately after treatment. These effects correlated with a dose-dependent delay in cell population growth rate. However, following treatment with concentrations of the anti-metabolites which failed to reduce colony-forming ability, control cell population growth rate ultimately resumed. Increasing the dose of methotrexate to 10^-4 M resulted in a reduction in MCF-7 cell colony-forming ability, inhibition of [³H]-thymidine incorporation into DNA and a fall in cell number within three days of treatment. Thymidine failed to modulate the growth inhibitory effects of the two antimetabolites. It is concluded that methotrexate and 5-fluorouracil appear to exert a cytostatic rather than a cytotoxic effect on MCF-7 cells.