DNA methylation by dimethyl sulfoxide and methionine sulfoxide triggered by hydroxyl radical and implications for epigenetic modifications.

Abstract

In this Letter, we demonstrate the formation of m(5)dC from dC or in DNA by dimethylsulfoxide (DMSO) and methionine sulfoxide (MetO), under physiological conditions in the presence of the Fenton reagent in vitro. DMSO reportedly affects the cellular epigenetic profile, and enhances the metastatic potential of cultured epithelial cells. The methionine sulfoxide reductase (Msr) gene was suggested to be a metastatis suppressor gene, and the accumulation of MetO in proteins may induce metastatic cancer. Our findings are compatible with these biological data and support the hypothesis that chemical cytosine methylation via methyl radicals is one of the mechanisms of DNA hypermethylation during carcinogenesis. In addition to m(5)dC, the formation of 8-methyldeoxyguanosine (m(8)dG) was also detected in DNA under the same reaction conditions. The m(8)dG level in human DNA may be a useful indicator of DNA methylation by radical mechanisms.

• Authors: Kazuaki Kawai, Yun-Shan Li, Ming-Fen Song, Hiroshi Kasai
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 20 Issue 1 Pg. 260-5 (Jan 01 2010) ISSN: 1464-3405 [Electronic] England
• PMID: 19914833 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Elsevier Ltd. All rights reserved.

Chemical References

• Fenton's reagent
• Hydroxyl Radical
• DNA
• Methionine
• Hydrogen Peroxide
• Iron
• methionine sulfoxide
• Dimethyl Sulfoxide

Topics

• Chromatography, High Pressure Liquid
• DNA (genetics, metabolism)
• DNA Methylation
• Dimethyl Sulfoxide (chemistry)
• Epigenesis, Genetic
• Humans
• Hydrogen Peroxide (chemistry)
• Hydroxyl Radical (chemistry)
• Iron (chemistry)
• Methionine (analogs & derivatives, chemistry)
• Tandem Mass Spectrometry