ArticleNucleic acids research2014
Quantitative determination of decitabine incorporation into DNA and its effect on mutation rates in human cancer cells.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- RRM1 inhibition sensitizes lung adenocarcinoma to decitabine treatment.Cell death & disease · 2026Article
- The type of DNA damage response after decitabine treatment depends on the level of DNMT activity.Life science alliance · 2024Article
- DNA methyltransferase inhibitor exposure-response: Challenges and opportunities.Clinical and translational science · 2023Review
- Venetoclax with decitabine or azacitidine in the first-line treatment of acute myeloid leukemia.EJHaem · 2023Article
- Mechanisms of myeloid leukemogenesis: Current perspectives and therapeutic objectives.Blood reviews · 2023Review
- Pharmacologic Induction of BRCAness inCancers · 2022Review
- Orthotopic Transplantation of Human Paediatric High-Grade Glioma in Zebrafish Larvae.Brain sciences · 2022Article
- Epigenetic Anti-Cancer Treatment With a Stabilized Carbocyclic Decitabine Analogue.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Hairpin-bisulfite sequencing of cells exposed to decitabine documents the process of DNA demethylation.Epigenetics · 2021Article
- Small Molecule Treatments Improve Differentiation Potential of Human Amniotic Fluid Stem Cells.Frontiers in bioengineering and biotechnology · 2021Article
- Lineage tracing of acute myeloid leukemia reveals the impact of hypomethylating agents on chemoresistance selection.Nature communications · 2019Article
- Tracking Decitabine Incorporation into Malignant Myeloid Cell DNA in vitro and in vivo by LC-MS/MS with Enzymatic Digestion.Scientific reports · 2019Article
- Intermediate-term memory inLearning & memory (Cold Spring Harbor, N.Y.) · 2018Article
- AZA-MS: a novel multiparameter mass spectrometry method to determine the intracellular dynamics of azacitidine therapy in vivo.Leukemia · 2018Article
- Enhancing the Cytotoxic Effects of PARP Inhibitors with DNA Demethylating Agents - A Potential Therapy for Cancer.Cancer cell · 2016Article
- 5-Azacytidine suppresses EC9706 cell proliferation and metastasis by upregulating the expression of SOX17 and CDH1.International journal of molecular medicine · 2016Article
- Simultaneous quantitative determination of 5-aza-2'-deoxycytidine genomic incorporation and DNA demethylation by liquid chromatography tandem mass spectrometry as exposure-response measures of nucleoside analog DNA methyltransferase inhibitors.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2016Article
- Lack of mutational hot spots during decitabine-mediated HIV-1 mutagenesis.Antimicrobial agents and chemotherapy · 2015Article
- The hypomethylating agent Decitabine causes a paradoxical increase in 5-hydroxymethylcytosine in human leukemia cells.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Decitabine (5-aza-2'-deoxycytidine) is a DNA methyltransferase inhibitor and an archetypal epigenetic drug for the therapy of myeloid leukemias. The mode of action of decitabine strictly depends on the incorporation of the drug into DNA. However, DNA incorporation and ensuing genotoxic effects of decitabine have not yet been investigated in human cancer cell lines or in models related to the approved indication of the drug. Here we describe a robust assay for the quantitative determination of decitabine incorporation rates into DNA from human cancer cells. Using a panel of human myeloid leukemia cell lines we show appreciable amounts of decitabine incorporation that closely correlated with cellular drug uptake. Decitabine incorporation was also detectable in primary cells from myeloid leukemia patients, indicating that the assay is suitable for biomarker analyses to predict drug responses in patients. Finally, we also used next-generation sequencing to comprehensively analyze the effects of decitabine incorporation on the DNA sequence level. Interestingly, this approach failed to reveal significant changes in the rates of point mutations and genome rearrangements in myeloid leukemia cell lines. These results indicate that standard rates of decitabine incorporation are not genotoxic in myeloid leukemia cells.
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