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Korean J Parasitol > Volume 28(2):1990 > Article

Original Article
Korean J Parasitol. 1990 Jun;28(2):79-84. English.
Published online Mar 20, 1994.  http://dx.doi.org/10.3347/kjp.1990.28.2.79
Copyright © 1990 by The Korean Society for Parasitology
Effects of pyrimidine salvage inhibitors on uracil incorporation of Toxoplasma gondii
J H Youn,H W Nam,D J Kim and W Y Choi
Department of Parasitology, Catholic University Medical College, Seoul 131-701, Korea.
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.

Figures


Fig. 1
Inhibition of uracil incorporation by dihydrofolate reductase inhibitors in Toxoplasma gondii. Various concentrations of inhibitors, pyrimethamine (▪) and methotrexate (□ during the time of co-culture were treated. Effects of inhibitors were described as a percent ratio of isotopic uracil uptake to control which was not treated.


Fig. 2
Effects of pyrimethamine (•,◦) and methotrexate (▪,▫) on thymidine incorporation in Toxoplasma-infected HL-60 cells (-) and HL-60 cells alone (…).


Fig. 3
Inhibition of uracil incorporation by thymidylate synthase inhibitors in Toxoplasma gondii. Various concentrations of inhibitors, fluoro-uridine (-▪-), fluoro-dUMP (-▫-) and fluorouracil (-◦-) were treated. Effects of inhibitors were described as a percent ratio of isotopic uracil uptake to control which was not treated.


Fig. 4
Effects of azauridine on uracil incorporation of Toxoplasma gondii (-•-) and HL-60 cells (-▪-).

Tables


Table 1
Acute effects of inhibitors with the concentration which diminish the uracil incorporation to 50% of control group

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