Analyses of 8-Methyldeoxyadenosine and 8-Methyldeoxyguanosine as Markers of Free Radical-mediated DNA Methylation in Mouse

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  • Kasai Hiroshi
    Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health
  • Kawai Kazuaki
    Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health
  • Song Ming-Fen
    Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health
  • Li Yun-Shan
    Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health
  • Hattori Tomomi
    Research Center for Environmental Quality Management, Kyoto University
  • Matsuda Tomonari
    Research Center for Environmental Quality Management, Kyoto University

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説明

To examine whether methyl radical-induced DNA damage occurs in vivo, cumene hydroperoxide (CuOOH) and methionine sulfoxide (MetO) were administered to mice as methyl radical generators, and 8-methyldeoxyadenosine (m8dA) and 8-methyldeoxyguanosine (m8dG) in the tissue DNA were analyzed by the LC/MS/MS method. After mouse skin was treated with CuOOH and Fe2+, both m8dA and m8dG were detected in the epidermal DNA. m8dA formation was also detected in the liver DNA from MetO-treated, non-alcoholic steatohepatitis (NASH) mice. Since 5-methyldeoxycytidine, m8dA, and m8dG are formed in DNA by methyl radicals, these results support our hypothesis that de novo DNA methylation at the cytosine C-5 position is triggered by a free radical mechanism and may initiate epigenetic changes.<br>

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