Abstract
SCHISTOSOMES seem to depend primarily if not exclusively on the anabolism of preformed purines for their total purine nucleotide requirements (ref. 1 and our own unpublished observations). Among various purine analogues we tested against Schistosoma mansoni in vitro, tubercidin (7-deazaadeno-sine)2 was the most active, causing early separation of paired adults, alterations of the muscular activity pattern, and inhibition of egg laying in the medium when present in a concentration as low as 10−7 M. When administered to S. mansoni-infested mice either intraperitoneally or orally, tubercidin in effective dose regimens invariably caused 20–30% mortality. In an attempt to increase the margin of safety of this potentially useful antischistosomal agent, we considered the following facts in planning a new strategy of treatment. Schistosomes feed on blood cells, beginning about 2 weeks after cercarial penetration of the host3. Tubercidin is rapidly absorbed into red cells in vitro and is sequestered intracellularly in a phosphorylated form4. From 0.2–0.4 mg of tubercidin/ml. of whole blood can be so sequestered, and the longevity of tubercidin-containing red cells is unaffected4. We have investigated whether host red cells could deliver tubercidin to haematophagous forms of schistosomes, thereby increasing the selective toxicity of this antibiotic.
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JAFFE, J., MEYMARIAN, E. & DOREMUS, H. Antischistosomal Action of Tubercidin administered after Absorption into Red Cells. Nature 230, 408–409 (1971). https://doi.org/10.1038/230408a0
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DOI: https://doi.org/10.1038/230408a0
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