1-5-formyltetrahydrofolate and 1-5-methyltetrahydrofolate rescue in L-1210 leukemia treated with high methotrexate doses

Highly purified 5-l-methyltetrahydrofolate (m-THF) and 5-l-formyl-THF (f- THF) preparations were compared for rescuing from methotrexate (MTX) toxicity in DBA2 mice transplanted with L1210 leukemia. Mice received two doses of reduced folates (2 mg/kg, s.c.) 16 and 24 h after a single s.c. MTX dose. f- THF was 1.8 time more effective than m-THF in protecting tumor cells from MTX (800 mg/kg). This MTX dose caused a 57% fall in circulating polymorphonucleates, which was prevented by both reduced folates. Treatment with 800 mg/kg of MTX plus m-THF was 1.5 fold more effective than the same MTX dose plus f-THF in increasing survival time of tumor-bearing mice. These data suggest a higher selectivity and efficacy of l-m-THF with respect to l- f-THF in rescuing from MTX toxicity.