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.

authors

Rosemond-Hornbeak H,Nair MG

doi

10.1128/aac.15.5.730

subject

Has Abstract

pub_date

1979-05-01 00:00:00

pages

730-4

issue

5

eissn

0066-4804

issn

1098-6596

journal_volume

15

pub_type

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