Rescue effect of exogenous reduced folates on methotrexate polyglutamylation and dihydrofolate reductase activity in L1210 cells.
L1210 can be rescued from exposure to an inhibitory effect of methotrexate (MTX) by subsequent addition of 5-formyltetrahydrofolate, 5-methyltetrahydrofolate or dihydrofolate. All folates listed caused marked reduction of long-chain MTX polyglutamates content and increased the activity of dihydrofolate reductase. This indicates that the rescue is a result of interaction of the reduced folates with two processes-polyglutamylation of MTX and generation of dihydrofolate.
Balińska
M
M
Department of Cellular Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences.
D000818:Animals; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005575:Formyltetrahydrofolates / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000378:metabolism / Q000473:pathology; D008727:Methotrexate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D010455:Peptides / Q000378:metabolism*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000378:metabolism*; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism*; D013763:Tetrahydrofolates / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D005575:Formyltetrahydrofolates; D010455:Peptides; D013763:Tetrahydrofolates; D011099:Polyglutamic Acid; C010920:dihydrofolate; C014085:methotrexate polyglutamate; D005492:Folic Acid; D013762:Tetrahydrofolate Dehydrogenase; C005984:5-methyltetrahydrofolate; D008727:Methotrexate