Abstract
Incubation of phytohemagglutinin-stimulated normal human lymphocytes with diphenylhydantoin (DPH). 100 µg/ml (3.6 x 10-4 M), for one hour inhibited incorporation of six radioisotopic precursors of deoxyribonucleic acid, ribonucleic acid, protein. lipid and nucleotides. In all cases the inhibition was similar. Other anticonvulsants had lesser effects on uptake of thymidine and leucine into deoxyribonucleic acid and protein with the exception of 3-allyl-5-isobutyl-2-thiohydantoin (CO-ORD). Assay for folate antagonism using an estimate of thymidylate biosynthesis showed that DPH did not have an antifolate effect. Assay of adenosine triphosphatase showed that enzyme activity was inhibited by DPH, 100 µg/ml (3.6 x 10-4 M) but not by lower concentrations. We concluded that membrane transport may account for the effect of DPH at suprapharmacologic concentrations although the mechanism of its inhibition of thymidine incorporation at pharmacologic concentrations remains unknown.
Footnotes
- Received May 4, 1972.
- Accepted February 23, 1973.
- © 1972 by The Williams & Wilkins Co.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|