Abstract 4422: Methylcytosine topology: potential of a DNA landmark in pre-clinical epigenetic drug toxicology
Abstract Cellular reprogramming through drug-based epigenetic intervention has become a novel approach in the treatment of complex diseases and in regenerative medicine towards reconstitution of normal cell, tissue and organ function. Within this context, non-specific and off-target global DNA demet...
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| Published in | Cancer research (Chicago, Ill.) Vol. 73; no. 8_Supplement; p. 4422 |
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| Main Author | |
| Format | Journal Article |
| Language | English |
| Published |
15.04.2013
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| Online Access | Get full text |
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| Summary: | Abstract
Cellular reprogramming through drug-based epigenetic intervention has become a novel approach in the treatment of complex diseases and in regenerative medicine towards reconstitution of normal cell, tissue and organ function. Within this context, non-specific and off-target global DNA demethylation — either directly induced by DNA demethylating drugs or indirectly caused by histone modifiers or any other agent with epigenetic consequences — could impact the cells’ DNA methylation pattern and lead to unwanted cryptic DNA methylation toxicity and carcinogenesis: by influencing chromatin conformation, genome organization, and cellular gene expression programs. The Translational Cytomics Group at the Cedars-Sinai Medical Center (Los Angeles) has developed 3D quantitative DNA Methylation Imaging (3D-qDMI), a non-disruptive image-cytometrical method that measures the differential load and spatial distribution of methylated cytosine (MeC) within individual nuclei of thousands of cells in a cell-by-cell fashion. Thus the technology has the additional capability of capturing cellular heterogeneity regarding global DNA methylation properties in response to drug exposure. Utilizing 3D-qDMI we are currently evaluating these topological parameters, which translate to differential DNA methylation phenotypes (MeC phenotypes), as potential chromatin signatures (textures) to be utilized in the characterization of cells during reprogramming, and for genotoxicity assessment of drugs.
Citation Format: Jian Tajbakhsh. Methylcytosine topology: potential of a DNA landmark in pre-clinical epigenetic drug toxicology. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4422. doi:10.1158/1538-7445.AM2013-4422 |
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| ISSN: | 0008-5472 1538-7445 |
| DOI: | 10.1158/1538-7445.AM2013-4422 |