An apparent relationship between responsiveness to folinic acid protection from methotrexate cytotoxicity and uptake of 5-methyltetrahydrofolate in a series of murine cell lines.

The ability of CF to protect cells from methotrexate toxicity was measured in a series of murine lymphoma cells of varying degrees of sensitivity to methotrexate. The cells that were the most resistant to methotrexate showed the least degree of protection from methotrexate cytotoxicity. The extent of protection afforded by CF was found to correlate with the capacity of the cells to take up C14-5-methyltetrahydrofolate. That is, the cells with the lowest extent of uptake of reduced folate were afforded the least degree of protection from methotrexate by CF.