AZT-induced hypermethylation of human thymidine kinase gene in the absence of total DNA hypermethylation.
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.
Lucarelli
M
M
Department of Human Biopathology, University of Rome La Sapienza, Italy.
Palitti
F
F
Carotti
D
D
Cianfriglia
M
M
Signoretti
C
C
Bozzi
A
A
Strom
R
R
D044503:5-Methylcytosine; D000998:Antiviral Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003596:Cytosine / Q000031:analogs & derivatives / Q000032:analysis; D019175:DNA Methylation / Q000187:drug effects*; D019003:Deoxyribonuclease HpaII; D004351:Drug Resistance; D005091:Exons; D006801:Humans; D016133:Polymerase Chain Reaction; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism; D015215:Zidovudine / Q000494:pharmacology*
D000998:Antiviral Agents; D015215:Zidovudine; D044503:5-Methylcytosine; D003596:Cytosine; D013937:Thymidine Kinase; D019003:Deoxyribonuclease HpaII