Induction of differentiation and inhibition of DNA methylation in HL-60 myeloid leukemic cells by 5-AZA-2'-deoxycytidine. 1985

R L Momparler, and J Bouchard, and J Samson

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.

UI MeSH Term Description Entries
D008745 Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed) Methylations
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004121 Dimethyl Sulfoxide A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during CRYOPRESERVATION. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation. DMSO,Dimethyl Sulphoxide,Dimethylsulfoxide,Dimethylsulphinyl,Dimethylsulphoxide,Dimexide,Rheumabene,Rimso,Rimso 100,Rimso-50,Sclerosol,Sulfinylbis(methane),Rimso 50,Rimso50,Sulfoxide, Dimethyl,Sulphoxide, Dimethyl
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077209 Decitabine An azacitidine derivative and antineoplastic antimetabolite. It inhibits DNA methyltransferase to re-activate silent genes, limiting METASTASIS and NEOPLASM DRUG RESISTANCE. Decitabine is used in the treatment of MYELODISPLASTIC SYNDROMES, and ACUTE MYELOID LEUKEMIA. 2'-Deoxy-5-azacytidine,5-Aza-2'-deoxycytidine,5-AzadC,5-Azadeoxycytidine,5-Deoxyazacytidine,5AzadC,AzadC Compound,Dacogen,Decitabine Mesylate,NSC 127716,NSC-127716,2' Deoxy 5 azacytidine,5 Aza 2' deoxycytidine,5 Azadeoxycytidine,5 Deoxyazacytidine,Compound, AzadC,Mesylate, Decitabine,NSC127716
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D001374 Azacitidine A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent. Azacytidine,5-Azacytidine,NSC-102816,Vidaza,5 Azacytidine,NSC 102816,NSC102816

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