l-5-formyltetrahydrofolate and l-5-methyltetrahydrofolate rescue in L1210 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.
Simile
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MM
Istituto di Patologia Generale, Università di Sassari, Italy.
DeMiglio
M R
MR
Nufris
A
A
Pascale
R M
RM
Muroni
M R
MR
Feo
F
F
D000818:Animals; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use*; D007939:Leukemia L1210 / Q000188:drug therapy*; D008727:Methotrexate / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D013763:Tetrahydrofolates / Q000008:administration & dosage / Q000627:therapeutic use*
D013763:Tetrahydrofolates; D002955:Leucovorin; C005984:5-methyltetrahydrofolate; D008727:Methotrexate