Abstract
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 μg/ml, whereas those of nucleobases, leucine, choline and glucose are unaltered at the maximum nontoxic dose of B-31 (25 μg/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.
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Abbreviations
- BVDU:
-
5-bromovinyl-2′-deoxyuridine
- HSV-1:
-
herpes simplex virus type 1
- HIV-1:
-
human immunodeficiency virus type 1
- NBMPR:
-
nitrobenzythioinosine, 6-[(4-nitrobenzyl)thio]-9-8-D-ribofurannosylpurine
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Pani, A., Obino, P., Guarracino, P. et al. The antimitotic drug 4,6-dimethyl-2-amino-3,4,5-trimethoxyphenyl-pyrimidine inhibits the nucleoside transport system of cells from various animal species. Experientia 50 (Suppl 1), 29–33 (1994). https://doi.org/10.1007/BF01992045
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DOI: https://doi.org/10.1007/BF01992045