Back to Search
Start Over
Heavy Metals Induce Decline of Derivatives of 5-Methycytosine in Both DNA and RNA of Stem Cells
- Source :
- ACS chemical biology. 12(6)
- Publication Year :
- 2017
-
Abstract
- Toxic heavy metals have been considered to be harmful environmental contaminations. The molecular mechanisms of heavy-metals-induced cytotoxicity and carcinogenicity are still not well elucidated. Previous reports showed exposures to toxic heavy metals can cause a change of DNA cytosine methylation (5-methylcytosine, 5-mC). However, it is still not clear whether heavy metals have effects on the recently identified new epigenetic marks in both DNA and RNA, i.e., 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and 5-carboxylcytosine (5-caC). Here, we established a chemical labeling strategy in combination with liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS) analysis for highly sensitive detection of eight modified cytidines in DNA and RNA. The developed method allowed simultaneous detection of all eight modified cytidines with improved detection sensitivities of 128-443-fold. Using this method, we demonstrated that the levels of 5-hmC, 5-foC, and 5-caC significantly decreased in both the DNA and RNA of mouse embryonic stem (ES) cells while exposed to arsenic (As), cadmium (Cd), chromium (Cr), and antimony (Sb). In addition, we found that treatments by heavy metals induced a decrease of the activities of 10-11 translocation (Tet) proteins. Furthermore, we revealed that a content change of metabolites occurring in the tricarboxylic acid cycle may be responsible for the decline of the derivatives of 5-mC. Our study shed light on the epigenetic effects of heavy metals, especially for the induced decline of the derivatives of 5-mC in both DNA and RNA.
- Subjects :
- 0301 basic medicine
Biology
Tandem mass spectrometry
01 natural sciences
Biochemistry
Epigenesis, Genetic
03 medical and health sciences
chemistry.chemical_compound
Cytosine
Mice
Tandem Mass Spectrometry
Metals, Heavy
Animals
Epigenetics
Cytotoxicity
Carcinogen
Cells, Cultured
Stem Cells
010401 analytical chemistry
RNA
General Medicine
DNA
DNA Methylation
Molecular biology
0104 chemical sciences
030104 developmental biology
chemistry
DNA methylation
5-Methylcytosine
Molecular Medicine
Stem cell
Subjects
Details
- ISSN :
- 15548937
- Volume :
- 12
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- ACS chemical biology
- Accession number :
- edsair.doi.dedup.....55754d203a425f5e9cda3b3bbaf02c23