Dideoxycytidine, an anti-HIV drug, selectively inhibits growth but not phosphatidylcholine metabolism in neuroblastoma and glioma cells.
Dideoxycytidine (ddCyd), an inhibitor of AIDS-related HIV, has been examined for effects on cell proliferation and phosphatidylcholine synthesis in tumor lines of nervous system origin. Uptake and metabolism of [3H]ddCyd, observed in all cells, was greatest in one human neuroblastoma line, HTB-10. Growth of the HTB-10 line was markedly inhibited by 40 microM ddCyd, whereas growth of C6 glioma and N1E-115 or HTB-11 neuroblastoma cells was unaltered. Phosphatidylcholine synthesis in the presence or absence of stimulation by phorbol ester was not specifically altered by ddCyd. Thus, ddCyd was incorporated and inhibited growth in a cell-specific manner but had little effect on cytidine-dependent phospholipid synthesis. This suggests that some cells derived from the nervous system may be more susceptible than others with respect to the positive and negative effects of ddCyd as a potential antiviral drug.
Cook
H W
HW
Atlantic Research Centre for Mental Retardation, Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
Spence
M W
MW
D002455:Cell Division / Q000187:drug effects; D015224:Dideoxynucleosides / Q000494:pharmacology*; D005910:Glioma; D006801:Humans; D009447:Neuroblastoma; D010713:Phosphatidylcholines / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism*; D016047:Zalcitabine
D015224:Dideoxynucleosides; D010713:Phosphatidylcholines; D016047:Zalcitabine