A basis for fluoropyrimidine-induced antagonism to methotrexate in Ehrlich ascites tumor cells in vitro.
The inhibitory effect of methotrexate on [3H]deoxyuridine incorporation into DNA is reduced as the basal rate of this reaction is inhibited by pretreatment of Ehrlich ascites tumor cells with fluoropyrimidines. This observation is a basis for fluoropyrimidine-methotrexate antagonism in anticancer regimens and supports the concept that the sensitivity of thymidylate synthesis in tumor cells to methotrexate is related, in part, to the basal rate of thymidylate synthesis from deoxyuridylate.
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D003857:Deoxyuridine / Q000378:metabolism; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000494:pharmacology; D066298:In Vitro Techniques; D008727:Methotrexate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051379:Mice; D011743:Pyrimidines / Q000494:pharmacology*; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D013763:Tetrahydrofolates / Q000378:metabolism; D013938:Thymidine Monophosphate / Q000096:biosynthesis
D004273:DNA, Neoplasm; D011743:Pyrimidines; D013763:Tetrahydrofolates; D013938:Thymidine Monophosphate; D013762:Tetrahydrofolate Dehydrogenase; D005472:Fluorouracil; D003857:Deoxyuridine; D008727:Methotrexate