The antimitotic drug 4,6-dimethyl-2-amino-3,4,5- trimethoxyphenyl-pyrimidine inhibits the nucleoside transport system of cells from various animal species.
4,6-dimethyl-2-amino-3,4,5-trimethoxyphenyl-pyrimidine (B-31) is a pyrimidine derivative previously reported to arrest the mitotic cycle of mammalian cells in metaphase. In the present study it is shown that B-31 also acts as a specific inhibitor of the cellular uptake of nucleosides. The uptake of purinic and pyrimidinic nucleosides is inhibited by 80-90% at concentrations in the range 5-20 micrograms/ml, whereas those of nucleobases, leucine, choline and glucose are unaltered at the maximum nontoxic dose of B-31 (25 micrograms/ml). Various mammalian (human, monkey and murine) and avian cell are equally sensitive to the inhibition of nucleoside transport. The antimitotic effect of B-31, by contrast, is species-specific: human cells are the most sensitive whereas monkey and chicken fibroblasts appear resistant to this effect. Both effects can be reversed by removal of B-31 from the medium; inhibition of nucleoside transport can also be reversed by high doses of the nucleosides themselves.
Pani
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Obino
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Guarracino
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La Colla
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D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D003839:Deoxyadenosines / Q000494:pharmacology; D003849:Deoxyguanosine / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D009705:Nucleosides / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*; D013045:Species Specificity; D027981:Symporters; D014529:Uridine / Q000378:metabolism / Q000494:pharmacology; D014709:Vero Cells
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D003839:Deoxyadenosines; D009705:Nucleosides; D011743:Pyrimidines; D027981:Symporters; C073034:sodium-nucleoside cotransporter; C012626:B 31; D003849:Deoxyguanosine; D014529:Uridine