New approach to antifolate treatment of certain cancers as demonstrated in tissue culture.
The selective toxicity of antifolates for a variety of cancers can be improved, as illustrated by the combined administration of N5-methyltetrahydrofolate and methotrexate in tissue culture. When a variety of neoplastic cell types characterized by a deficiency of vitamin B12-dependent N5-methyltetrahydrofolate methyltransferase (5-methyltetrahydropteroyl-L-glutamate:L-homocysteine S-methyltransferase, EC 2.1.1.13) and normal adult cells are grown in media containing methotrexate and either N5-methyltetrahydrofolate or N5-formyltetrahydrofolate, not only is the selective toxicity of methotrexate demonstrated, but the advantage of using N5-methyltetrahydrofolate in place of N5-formyltetrahydrofolate is also revealed. The implications and applications of this particular combination in the treatment of human cancer are discussed.
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects; D008727:Methotrexate / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D051381:Rats; D013763:Tetrahydrofolates / Q000494:pharmacology / Q000627:therapeutic use*
D013763:Tetrahydrofolates; D002955:Leucovorin; D008727:Methotrexate