Inhibition of nucleic acid synthesis by the DI-n-butyl ester of methotrexate

Abstract The effects of dibutyl methotrexate (DBMTX) on the incorporation into DNA of labelled deoxynucleosides have been studied in a variety of cultured cell lines. In serum-free conditions DBMTX consistently inhibited thymidine and deoxyuridine incorporation. Prior incubation of DBMTX in 10% mouse serum abolished the inhibition of thymidine incorporation but did not influence the inhibition of deoxyuridine incorporation. Identical results were observed in cell lines resistant to methotrexate because of increased levels of dihydrofolate reductase or altered drug transport characteristics. Citrovorum factor prevented only partially the effects of DBMTX in serum-free cultures.