6533b838fe1ef96bd12a4879
RESEARCH PRODUCT
The DNA methylation inhibitor 5-azacytidine modulates 6-thioguanine toxicity in mammalian cells
Giusi BarbataFabio CaradonnaGiulia Sciandrellosubject
Antimetabolites AntineoplasticHypoxanthine Phosphoribosyltransferasemedicine.drug_classCell SurvivalCellHamsterToxicologyAntimetaboliteChinese hamster6-thioguanineCricetulus5-azacytidineCricetinaeAntineoplastic Combined Chemotherapy ProtocolsmedicineAnimalsThioguanineCells CulturedbiologyCell growthtoxicityDrug SynergismGeneral MedicineDNAProdrugDNA Methylationbiology.organism_classificationMolecular biologySettore BIO/18 - Geneticamedicine.anatomical_structureBiochemistryCell cultureToxicityAzacitidineSister Chromatid ExchangeCell Divisiondescription
In order to assess the effects of combining two antimetabolites used separately to treat human leukemias, we carried out an experimental study by exposing V79 Chinese hamster cells, a 6-thioguanine (6-tG)-sensitive cell line, to sequential and concurrent treatments with 5-azacytidine (5-azaC) and 6-tG. In this paper, we demonstrate that there is a clear dependency for the way in which this combination was tested. Pre-treatment with 5-azaC made V79 cells more resistant to 6-tG by a substantial reduction in 6-tG incorporation into DNA; this effect could still be detected for several cell divisions after the removal of 5-azaC, and was achieved neither by reduced cell growth nor by the induction of hypoxanthine-guanine-phosphoribosyltransferase (HGPRT(-)) mutants. The reverse order of treatment produced a higher toxic effect than exposure to each prodrug alone. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2003-04-30 |