AZT‐induced hypermethylation of human thymidine kinase gene in the absence of total DNA hypermethylation

FEBS Letters

Cianfriglia, Maurizio³  Lucarelli, Marco⁴  Signoretti, Claudia³  Bozzi, Argante²  Carotti, Daniela¹  Strom, Roberto⁴  Palitti, Franco¹ 

[1] Department of Biochemical Sciences ‘A.Rossi Fanelli’, University of Rome ‘La Sapienza’, Rome, Italy;Department of Biomedical Sciences and Technology, University of L'Aquila, L'Aquila, Italy;Immunology Laboratory, Istituto Superiore di Sanità, Rome, Italy;Department of Human Biopathology, University of Rome ‘La Sapienza’, Rome, Italy

关键词: 3′-Azido-3′-deoxythymidine;    Drug resistance;    DNA methylation;    Thymidine kinase gene;    HpaII/PCR assay;    AZT;    3′-azido-3′-deoxythymidine;    TK;    thymidine kinase;    RT;    reverse transcriptase;    AZT-MP;    AZT monophosphate;    AZT-TP;    AZT triphosphate;    FCS;    fetal calf serum;    MTT;    3-(4;    5-dimethylthiazol-2-yl)-2;    5-diphenyltetrazolium bromide;   

DOI  :  10.1016/0014-5793(96)01124-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Genome-wide DNA hypermethylation induced by 3′-azido-3′-deoxythymidine (AZT) has been suggested to be involved in the development of AZT resistance. We used a CD4 T-lymphoblastoid CEM line and its AZT-resistant MT500 variant with reduced thymidine kinase activity. Evaluation of total DNA methylation, after AZT treatment, failed to show an increase in the 5-methylcytosine level in both parental and AZT-resistant cells. The effect was instead observed at a more specific gene level, on the three HpaII sites present in exon 1 of the human thymidine kinase gene. These results suggest that AZT treatment can induce site-specific hypermethylation, even in the absence of a more general DNA hypermethylating effect.

【 授权许可】

Unknown