Protection of mice against lethal dosages of nebularine by nitrobenzylthioinosine, an inhibitor of nucleoside transport.
In the presence of nitrobenzylthioinosine (NBMPR) a potent inhibitor of nucleoside transport, Roswell Park Memorial Institute 6410 cells proliferating in culture were protected from otherwise inhibitory concentrations of 9-beta-D-ribofuranosylpurine (nebularine); cellular uptake of nebularine was greatly reduced under these circumstances. Initial rates of nebularine uptake by Roswell Park Memorial Institute 6410 cells were inhibited by NBMPR, indicating that the latter interfered with nebularine transport. NBMPR protected mice against potentially lethal treatment regimens with nebularine, 4-amino-7-(beta-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine (tubercidin) or 4-amino-5-cyano-7-(beta-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine (toyocamycin); protection resulted when NBMPR was administered i.p. in advance of or simultaneously with nebularine, but not when NBMPR followed nebularine by 1 hr. Both NBMPR and its 5'-monophosphate protected mice against nebularine lethality when administered s.c.
D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D005260:Female; D007288:Inosine / Q000031:analogs & derivatives*; D051379:Mice; D008815:Mice, Inbred Strains; D009705:Nucleosides / Q000378:metabolism; D011684:Purine Nucleosides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D012263:Ribonucleosides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D009705:Nucleosides; D011684:Purine Nucleosides; D012263:Ribonucleosides; D013868:Thioinosine; D007288:Inosine; C005248:nebularine; C001789:4-nitrobenzylthioinosine