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.