Murine erythroleukemia cells resistant to periodate-oxidized adenosine have lowered levels of nucleoside transporter.
The results above show that mammalian cells, as exemplified by MELC, can be selected to be resistant to Adox, and that the resistant cells have greatly decreased nucleoside transport capacity. Since no mutagen was used prior to the selection process and Adox resistance was genetically stable, it appears that within a population of normal cells there is a genetically controlled range of expression of the nucleoside transporter. On the basis of the present data we cannot determine if the low level of nucleoside transporter in AR MELC is due to an altered form of the protein or a decreased amount of the normal protein. However the similarity of the Kd for NBTI in normal and AR MELC suggests that the latter is the case. Considerable indirect evidence is presented that Adox, with its ribose converted to an acyclic dialdehyde, is a substrate for the nucleoside transporter, adding a new type of compound to this list.
Hoffman
J
J
Department of Biochemistry, University of Louisville, KY 40292.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D004351:Drug Resistance / Q000502:physiology; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D007942:Leukemia, Experimental; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D033703:Nucleoside Transport Proteins; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D008565:Membrane Proteins; D033703:Nucleoside Transport Proteins; C027579:periodate-oxidized adenosine; D013868:Thioinosine; D012435:S-Adenosylhomocysteine; C001789:4-nitrobenzylthioinosine; D000241:Adenosine