ArticleBMC pharmacology & toxicology2013
3-D DNA methylation phenotypes correlate with cytotoxicity levels in prostate and liver cancer cell models.
Article in BMC pharmacology & toxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Incorporating DNA Methyltransferase Inhibitors (DNMTis) in the Treatment of Genitourinary Malignancies: A Systematic Review.Targeted oncology · 2018Pooled it
- Highly sensitive noninvasive early lung cancer detection using DNA methylation topology in sputum-derived epithelial cells.JTCVS open · 2023Article
- Efficient automatic 3D segmentation of cell nuclei for high-content screening.BMC bioinformatics · 2022Article
- DNA methylation topology differentiates between normal and malignant in cell models, resected human tissues, and exfoliated sputum cells of lung epithelium.Frontiers in oncology · 2022Article
- CXCR4 Regulates Temporal Differentiation via PRC1 Complex in Organogenesis of Epithelial Glands.International journal of molecular sciences · 2021Article
- A Tox21 Approach to Altered Epigenetic Landscapes: Assessing Epigenetic Toxicity Pathways Leading to Altered Gene Expression and Oncogenic Transformation In Vitro.International journal of molecular sciences · 2017Review
- Rapid 3-D delineation of cell nuclei for high-content screening platforms.Computers in biology and medicine · 2016Article
- Dynamic heterogeneity of DNA methylation and hydroxymethylation in embryonic stem cell populations captured by single-cell 3D high-content analysis.Experimental cell research · 2015Article
- Critical role of lysine 134 methylation on histone H2AX for γ-H2AX production and DNA repair.Nature communications · 2014Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe spatial organization of the genome is being evaluated as a novel indicator of toxicity in conjunction with drug-induced global DNA hypomethylation and concurrent chromatin reorganization. 3D quantitative DNA methylation imaging (3D-qDMI) was applied as a cell-by-cell high-throughput approach to investigate this matter by assessing genome topology through represented immunofluorescent nuclear distribution patterns of 5-methylcytosine (MeC) and global DNA (4,6-diamidino-2-phenylindole = DAPI) in labeled nuclei.
methodsDifferential progression of global DNA hypomethylation was studied by comparatively dosing zebularine (ZEB) and 5-azacytidine (AZA). Treated and untreated (control) human prostate and liver cancer cells were subjected to confocal scanning microscopy and dedicated 3D image analysis for the following features: differential nuclear MeC/DAPI load and codistribution patterns, cell similarity based on these patterns, and corresponding differences in the topology of low-intensity MeC (LIM) and low in intensity DAPI (LID) sites.
resultsBoth agents generated a high fraction of similar MeC phenotypes across applied concentrations. ZEB exerted similar effects at 10-100-fold higher drug concentrations than its AZA analogue: concentration-dependent progression of global cytosine demethylation, validated by measuring differential MeC levels in repeat sequences using MethyLight, and the concurrent increase in nuclear LIM densities correlated with cellular growth reduction and cytotoxicity.
conclusions3D-qDMI demonstrated the capability of quantitating dose-dependent drug-induced spatial progression of DNA demethylation in cell nuclei, independent from interphase cell-cycle stages and in conjunction with cytotoxicity. The results support the notion of DNA methylation topology being considered as a potential indicator of causal impacts on chromatin distribution with a conceivable application in epigenetic drug toxicology.
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