Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Bioorg Med Chem Lett. 2010 Jan 1;20(1):260-5. doi: 10.1016/j.bmcl.2009.10.124. Epub 2009 Oct 30.
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.
在这封信件中，我们证明了在生理条件下，二甲基亚砜（DMSO）和甲硫氨酸亚砜（MetO）在 Fenton 试剂存在下，可将 dC 或在 DNA 中形成 m(5)dC。据报道，DMSO 会影响细胞的表观遗传特征，并增强培养上皮细胞的转移潜能。甲硫氨酸亚砜还原酶（Msr）基因被认为是一个转移抑制基因，蛋白质中 MetO 的积累可能会引发转移性癌症。我们的发现与这些生物学数据一致，并支持这样一种假设，即通过甲基自由基进行的化学胞嘧啶甲基化是致癌过程中 DNA 过度甲基化的机制之一。除了 m(5)dC，在相同的反应条件下，我们还在 DNA 中检测到了 8-甲基脱氧鸟苷（m(8)dG）的形成。人类 DNA 中的 m(8)dG 水平可能是自由基机制导致的 DNA 甲基化的有用指标。
