Turriziani Ombretta, Scagnolari Carolina, Bambacioni Federica, Bellomi Francesca, Focher Federico, Gentile Massimo, Antonelli Guido
Antivir Ther. 2002 Jun;7(2):105-11.
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.
已证明,用核苷类似物如3'-叠氮-3'-脱氧胸苷(齐多夫定)、2',3'-双脱氧胞苷(扎西他滨)和9-(2-膦酰甲氧基乙基)腺嘌呤(PMEA)进行长期治疗,可能会导致对其抗HIV活性产生抗性的细胞被选择出来。由于长期治疗,已产生了一种对2',3'-二脱氢-3'-脱氧胸苷(司他夫定)的抗病毒和细胞毒性活性具有抗性的人T淋巴母细胞系。这些细胞称为CEM司他夫定细胞,对齐多夫定也较不敏感。CEM司他夫定细胞获得的细胞/药理学抗性相对较低,并且似乎与胸苷激酶(TK)活性的降低相关,而不是与TK mRNA表达的降低相关。