title: Antifolate activity of isoaminopterin in HeLa cells.
abstract: The antifolate activity and the transport characteristics of isoaminopterin (IA) in HeLa cells were studied and compared with those of methotrexate (MTX). Both IA and MTX inhibited the incorporation of [2-(14)C]deoxyuridine into HeLa cell DNA by 50% at a concentration of 0.09 muM by 8 h postaddition of the compounds. Unlike MTX, the inhibition of DNA synthesis by IA was time dependent and reached a maximum at 24 h. IA-induced inhibition was due to interference with folate metabolism, since it could be completely reversed with N(5)-formyl-tetrahydrofolate. Competitive transport experiments between IA and either radiolabeled MTX or radiolabeled folate showed that IA preferentially uses the reduced folate/MTX transport system. IA inhibited MTX uptake by 50% at a concentration of 6.8 muM but had a negligible effect on folate transport.
mesh_terms: D000630:Aminopterin / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D005492:Folic Acid / Q000378:metabolism; D005493:Folic Acid Antagonists; D006367:HeLa Cells; D006801:Humans; D008727:Methotrexate / Q000378:metabolism; D013997:Time Factors
chemical_list: D005493:Folic Acid Antagonists; D004247:DNA; D005492:Folic Acid; D000630:Aminopterin; D008727:Methotrexate