Korean J Parasitol.  1990 Jun;28(2):79-84. 10.3347/kjp.1990.28.2.79.

Effects of pyrimidine salvage inhibitors on uracil incorporation of Toxoplasma gondii

• Youn JH
• Nam HW
• Kim DJ
• Choi WY

• KMID: 1043393
• DOI: http://doi.org/10.3347/kjp.1990.28.2.79

Abstract

Metabolic inhibitors which act in the process of pyrimidine salvage influenced on the uracil incorporation into nucleic acids of Toxoplasma. Inhibitors of dihydrofolate reductase, pyrimethamine and methotrexate, and inhibitors of thymidylate synthase, fluoro-uridine, fluoro-dUMP and fluoro-uracil, diminished isotopic uracil uptake in dose-dependent manners. Azauridine which suppresses de novo pyrimidine biosynthesis did not affect the salvage even in a relatively high dose. These results suggested that the activation of uracil salvage should be closely related with the function of TMP biosynthetic enzymes. The pattern of thymidine uptake had no differences between control HL-60 cells and Toxoplasma infected cells, which did not reflect the specific proliferation of Toxoplasma. It can be exploited to characterize the effects of various compounds related with the proliferation of Toxoplasma, especially its DNA synthesis.

MeSH Terms

DNA-biosynthesis
Tetrahydrofolate-Dehydrogenase-antagonists-and-inhibitors
Thymidylate-Synthetase-antagonists-and-inhibitors
Toxoplasma-growth-and-development
Uridine-pharmacology
*Methotrexate-pharmacology
*Pyrimethamine-pharmacology
*Toxoplasma-metabolism
*Uracil-metabolism
*Uridine-analogs-and-derivatives
Tetrahydrofolate-Dehydrogenase
Thymidylate-Synthetase
5-fluorouridine; Pyrimethamine
Uridine
Methotrexate
Uracil
DNA