Effects of methotrexate on folates in Krebs ascites and L1210 murine leukemia cells.
Changes in reduced folates upon exposure of Krebs ascites cells and L1210 murine leukemia cells to methotrexate (MTX) have been measured by stoichiometric entrapment of tissue methylenetetrahydrofolate into a stable ternary complex with thymidylate synthase and tritiated 5-fluoro-2'-deoxy-uridine-5'-monophosphate. Tetrahydrofolate and 5-methyltetrahydrofolate were determined after conversion to methylenetetrahydrofolate. In both tumor cell lines, treatment with methotrexate at levels which had little effect on methylenetetrahydrofolate and tetrahydrofolate concentrations resulted in nearly complete elimination of the methyltetrahydrofolate pool. Thus, an initial effect of methotrexate on folate metabolism appears to be on methyltetrahydrofolate.
D000818:Animals; D002287:Carcinoma, Krebs 2 / Q000378:metabolism*; D002478:Cells, Cultured; D005492:Folic Acid / Q000378:metabolism*; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000378:metabolism*; D008727:Methotrexate / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D013763:Tetrahydrofolates / Q000378:metabolism
D005493:Folic Acid Antagonists; D013763:Tetrahydrofolates; C030371:5,6,7,8-tetrahydrofolic acid; D005492:Folic Acid; C005984:5-methyltetrahydrofolate; D008727:Methotrexate