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

Abstract

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.