Accumulation and metabolism of adenallene by murine leukemia L1210 cells.
Accumulation of the anti-HIV agent adenallene was examined in murine leukemia L1210 cells. Initial studies indicated an unusual result: accumulation of labeled adenallene was enhanced by decreasing the temperature of incubation, and (at 37 degrees C) by extracellular adenine, but not adenosine, cytosine, or thymine. We found that these phenomena resulted from the rapid deamination of intracellular adenallene to hypoxallene. Exodus of the latter was impaired at low temperatures and antagonized by hypoxanthine, the deamination product of adenine. In the presence of a deaminase inhibitor, adenallene transport was temperature-insensitive and nonsaturable and not affected by nucleoside transport inhibitors (dilazep, nitrobenzylthioinosine, and dipyridamole). These results support the view that adenallene enters cells by diffusion and is deaminated to hypoxallene, whose exodus occurs via a temperature-sensitive process exhibiting some structural specificity. We found no evidence of adenallene phosphorylation in L1210 cells.
Kessel
D
D
Department of Pharmacology and Medicine, Wayne State University, Detroit, Michigan 48201.
Zemlicka
J
J
D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D001711:Biotransformation; D003596:Cytosine / Q000494:pharmacology; D007700:Kinetics; D007939:Leukemia L1210 / Q000378:metabolism*; D051379:Mice; D013696:Temperature; D013941:Thymine / Q000494:pharmacology; D014316:Tritium; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D014316:Tritium; C056909:adenallene; C010192:9-(2-hydroxy-3-nonyl)adenine; D003596:Cytosine; D000225:Adenine; D000241:Adenosine; D013941:Thymine