l-5-formyltetrahydrofolate and l-5-methyltetrahydrofolate rescue in L1210 leukemia treated with high methotrexate doses.

Abstract

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.

• Authors: M M Simile, M R DeMiglio, A Nufris, R M Pascale, M R Muroni, F Feo
• Journal: Research communications in chemical pathology and pharmacology (Res Commun Chem Pathol Pharmacol) Vol. 81 Issue 2 Pg. 251-4 (Aug 1993) ISSN: 0034-5164 [Print] United States
• PMID: 8210704 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tetrahydrofolates
• Leucovorin
• 5-methyltetrahydrofolate
• Methotrexate

Topics

• Animals
• Leucovorin (administration & dosage, therapeutic use)
• Leukemia L1210 (drug therapy)
• Methotrexate (administration & dosage, toxicity)
• Mice
• Mice, Inbred DBA
• Neoplasm Transplantation
• Tetrahydrofolates (administration & dosage, therapeutic use)