RT Journal Article
SR Electronic
T1 Deoxyuridine Incorporation as a Useful Measure of Methotrexate and Metoprine Uptake and Metabolic Effectiveness
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 607
OP 613
VO 16
IS 2
A1 SEDWICK, W. DAVID
A1 FYFE, MARY JO
A1 BROWN, OLIVER E.
A1 FRAZER, THOMAS A.
A1 KUTLER, MARC
A1 LASZLO, JOHN
YR 1979
UL http://molpharm.aspetjournals.org/content/16/2/607.abstract
AB This paper contrasts the inhibition of deoxyuridine incorporation by the lipid-soluble antifolate, DDMP, and methotrexate in the human lymphoblastoid cell line, WIL-2. It shows how deoxyuridine incorporation can be used as an indirect tool for assay of drug uptake and facilitates interpretation of experiments with labeled drugs. Whereas 1 µM methotrexate takes 15-30 minutes to maximally inhibit deoxyuridine incorporation, DDMP maximally inhibits incorporation within five seconds of addition to the cell culture. These protocols expand the potential of deoxyuridine-based assays in analysis of antifolate action and may be useful for in vitro testing of potential tumor responses to antifolates.