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 res istance. We used a CD4 T-lymphoblastoid CEM line and its AZT-resistant MT500 variant with reduced thymidine kinase activity, Evaluation of t otal 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 th e three HpaII sites present in exon 1 of the human thymidine kinase ge ne, These results suggest that AZT treatment can induce site-specific hypermethylation, even in the absence of a more general DNA hypermethy lating effect.