Metabolism of adenosine analogues by Schistosoma mansoni and the effect of nucleoside transport inhibitors.

Schistosoma mansoni incorporated tubercidin, nebularine, 9-deazaadenosine, 5'-deoxy-5'-iodo-2-fluoroadenosine, 7,9-dideaza-7-thiaadenosine and toyocamycin but not sangivamycin, 3'-deoxy-sangivamycin, or 1-methylformycin into their nucleotide pool after a 4-hr incubation in vitro. In contrast to mammalian systems, addition of nucleoside transport inhibitors nitrobenzylthioinosine 5'-monophosphate (NBMPR-P), dilazep, or benzylacyclouridine had no significant effect on the pattern of incorporation of these adenosine analogues. Dipyridamole, on the other hand, reduced, but did not prevent, the incorporation of these analogues into the nucleoside 5'-triphosphate pool. These results suggest that the transport of purine nucleosides in schistosomes is different from that of their mammalian hosts. Therefore, coadministration of a specific nucleoside transport inhibitor with tubercidin, nebularine, 9-deazaadenosine, 5'-deoxy-5'-iodo-2-fluoroadenosine, toyocamycin, or 7,9-dideaza-7-thiaadenosine may result in high selective toxicity against schistosomes, as was the case with the combination of tubercidin plus NBMPR-P [el Kouni et al., Proc. natn. Acad. Sci. U.S.A. 80, 6667 (1983); el Kouni et al., Biochem. Pharmac. 34, 3921 (1985)], by protecting the host but not the parasite from the toxicity of these analogues.