Arabinosyl Nucleosides Inhibit Toxoplasma gondii and Allow the Selection of Resistant Mutants

Abstract

Adenine arabinoside which inhibits the synthesis of DNA by intracellular T. gondii, is more inhibitory to the parasite than it is to cultured human fibroblast host cells. A single-step mutant of T. gondii that is 50-fold more resistant to adenine arabinoside was isolated after mutagenesis with N-methyl-N''-nitro-N-nitrosoguanidine. Cytosine arabinoside is notably more inhibitory to cultured human cells than it is to T. gondii. In infected cells treated with cytosine arabinoside and labeled with 3H-deoxyuridine nearly all of the label is specifically incorporated into the intracellular T. gondii.