DNA methylation by dimethyl sulfoxide and methionine sulfoxide triggered by hydroxyl radical and implications for epigenetic modifications.
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.
Kawai
Kazuaki
K
Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Li
Yun-Shan
YS
Song
Ming-Fen
MF
Kasai
Hiroshi
H
D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D044127:Epigenesis, Genetic; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D017665:Hydroxyl Radical / Q000737:chemistry*; D007501:Iron / Q000737:chemistry; D008715:Methionine / Q000031:analogs & derivatives* / Q000737:chemistry; D053719:Tandem Mass Spectrometry
C045076:Fenton's reagent; D017665:Hydroxyl Radical; D004247:DNA; D008715:Methionine; D006861:Hydrogen Peroxide; D007501:Iron; C013111:methionine sulfoxide; D004121:Dimethyl Sulfoxide