Induction of differentiation and inhibition of DNA methylation in HL-60 myeloid leukemic cells by 5-AZA-2′-deoxycytidine

Abstract

The effects of 5-AZA-2′-deoxycytidine (5-AZA-CdR) on the induction of morphological and biochemical differentiation and inhibition of DNA methylation of human HL-60 myeliod leukemic cells were investigated. 5-AZA-CdR at concentrations of 0.1–1 μg ml −1 for 48-h exposure produced significant morphological differentiation of HL-60 leukemic cells to a more mature phenotype, augmented the cell surface marker (OKMI) for mature granulocytes/monocytes and also increased the superoxide anion production. Under these same conditions 5-AZA-CdR inhibited the synthesis of 5-methylcytosine in DNA suggesting that there is a correlation between the induction of differentiation and inhibition of DNA methylation. At concentrations of 5-AZA-CdR that inhibit DNA methylation there was a marked decrease in colony-formation suggesting that the antileukemic action of this analog is related to the methylation of DNA.