2'-deoxy-5,6-dihydro-5-azacytidine-a less toxic alternative of 2'-deoxy-5-azacytidine. A comparative study of hypomethylating potential

0360024 - ÚOCHB 2012 RIV US eng J - Journal Article
Matoušová, Marika - Votruba, Ivan - Otmar, Miroslav - Tloušťová, Eva - Günterová, Jana - Mertlíková-Kaiserová, Helena
2'-deoxy-5,6-dihydro-5-azacytidine-a less toxic alternative of 2'-deoxy-5-azacytidine. A comparative study of hypomethylating potential.
Epigenetics. Roč. 6, č. 6 (2011), s. 769-776. ISSN 1559-2294. E-ISSN 1559-2308
R&D Projects: GA MŠMT 1M0508
Institutional research plan: CEZ:AV0Z40550506
Keywords : epigenetic therapy * nucleoside analogs * DNA methylation * 2'-deoxy-5-azacytidine * 2'-deoxy-5,6-dihydro-5-azacytidine
Subject RIV: CE - Biochemistry
Impact factor: 4.318, year: 2011

A comparative study of hypomethylating activities of a series of 5-azacytidine nucleosides: 5-azacytidine, 2´-deoxy-5-azacytidine and its alpha-anomer, 5,6-dihydro-5-azacytidine, 2´-deoxy-5,6-dihydro-5-azacytidine and its α-anomer, and of a 2-pyrimidone ribonucleoside (zebularine) was conducted. Methylation-specific PCR was employed to detect the efficiency of individual agents on cyclin-dependent kinase inhibitor 2B and thrombospondin-1 hypermethylated gene loci. Overall changes in DNA methylation level were quantified by direct estimation of 5-methyl-2´-deoxycytidine 5´-monophosphate by HPLC using digested genomic DNA. Flow cytometric analysis of cell cycle progression and apoptotic markers was used to determine cytotoxicity of the compounds. mRNA expression was measured using qRT-PCR. 2´-Deoxy-5,6-dihydro-5-azacytidine was found to be less cytotoxic and more stable than 2´-deoxy-5-azacytidine at the doses that induce comparable DNA hypomethylation and gene reactivation.
Permanent Link: http://hdl.handle.net/11104/0197675