Selection of a T-cell line resistant to stavudine and zidovudine by prolonged treatment with stavudine.
It has been demonstrated that prolonged treatment with nucleoside analogues, such as 3'-azido-3'-deoxythymidine (zidovudine), 2',3'-dideoxycytidine (zalcitabine) and 9-(2-phosphonylmethoxyethyl) adenine (PMEA), may cause selection of cells that are resistant to their anti-HIV activity. A human T-lymphoblastoid cell line that is resistant to the antiviral and cytotoxic activity of 2',3'-didehydro-3'-deoxythymidine (stavudine) has developed as a result of prolonged treatment. These cells, called CEMstavudine, are also less sensitive to zidovudine. The cellular/pharmacological resistance acquired by the CEMstavudine cells is relatively low and appears to correlate with a reduction in thymidine kinase (TK) activity, rather than with a decreased expression of TK mRNA.
Turriziani
Ombretta
O
Scagnolari
Carolina
C
Bambacioni
Federica
F
Bellomi
Francesca
F
Focher
Federico
F
Gentile
Massimo
M
Antonelli
Guido
G
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D024882:Drug Resistance, Viral; D006678:HIV / Q000187:drug effects / Q000502:physiology; D006801:Humans; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D018119:Stavudine / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000821:virology; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors / Q000235:genetics; D013997:Time Factors; D015215:Zidovudine / Q000494:pharmacology*
D019380:Anti-HIV Agents; D012333:RNA, Messenger; D015215:Zidovudine; D018119:Stavudine; D013937:Thymidine Kinase