Mechanism of action of 5-AZA-dC: induced DNA hypomethylation does not lead to aberrant gene expression in human leukemic CEM cells.
To understand the mechanism of action of 5-AZA-2'-deoxycytidine, a potent antineoplastic agent, we studied its effect in CEM cells on DNA methylation while monitoring coinciding changes in DNA, RNA and protein synthesis. At concentrations near the inhibitory concentration, the drug induced a profound reduction of DNA methylation. Effects on DNA and RNA synthesis were also noted at 24 and 48 h of treatment. However, at all concentrations assayed, no change in polypeptide composition as monitored by 2-D gel electrophoresis, were observed. That the cytotoxic effect of 5-AZA-deoxycytidine is due to changes in gene expression induced by DNA methylation reduction is not supported.
Bouchard
J
J
Institut national de la recherche scientifique-Santé, Pointe-Claire, Qc, Canada.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001374:Azacitidine / Q000494:pharmacology; D002460:Cell Line; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D000077209:Decitabine; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008745:Methylation; D009363:Neoplasm Proteins / Q000096:biosynthesis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D000077209:Decitabine; D001374:Azacitidine