Induction of differentiation and inhibition of DNA methylation in HL-60 myeloid leukemic cells by 5-AZA-2'-deoxycytidine.
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 myeloid leukemic cells were investigated. 5-AZA-CdR at concentrations of 0.1-1 microgram 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.
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Momparler
J
J
Bouchard
J
J
Samson
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D000077209:Decitabine; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D008745:Methylation; D013481:Superoxides / Q000378:metabolism
D000970:Antineoplastic Agents; D013481:Superoxides; D000077209:Decitabine; D004247:DNA; D001374:Azacitidine; D004121:Dimethyl Sulfoxide