title: Degree of methylation burden is determined by the exposure period to carcinogenic factors.
abstract: Aberrant DNA methylation accumulated in normal tissues, namely methylation burden, is associated with risk of carcinogenesis. The levels of methylation burden are known to be influenced by multiple factors, such as genetic factors and strengths of carcinogenic factors. However, the impact of the degree of exposure to a carcinogenic factor is still unclear. Here, using a Mongolian gerbil model of Helicobacter pylori (H. pylori)-induced gastritis, we aimed to clarify the impact of the degree of exposure on methylation burden in normal gastric tissues. DNA methylation levels of four CpG islands, HE6, SA9, SB5, and SD2, increased by H. pylori infection, depending upon the infection period. After eradication of H. pylori, DNA methylation levels decreased, but tended to be higher in gastric mucosae with a longer infection period. DNA molecules with dense methylation, but not those with sparse methylation, increased depending upon the infection period. DNA methylation levels of one of the four CpG islands, SA9, tended to be higher in gastric mucosae of gerbils infected with H. pylori, even 50 weeks after eradication than in those of non-infected gerbils. These results showed for the first time that the levels of methylation burden in normal tissues are influenced by the degree of exposure to a carcinogenic factor.
authors.affiliation: Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takeshima
authors.affiliation: Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Niwa
authors.affiliation: Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Toyoda
authors.affiliation: Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Wakabayashi
authors.affiliation: Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamashita
authors.affiliation: Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ushijima
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D002273:Carcinogens / Q000633:toxicity; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000166:cytology / Q000382:microbiology / Q000473:pathology*; D005756:Gastritis / Q000382:microbiology*; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000235:genetics* / Q000382:microbiology / Q000473:pathology*; D016480:Helicobacter pylori
chemical_list: D002273:Carcinogens
keywords: Aberrant DNA methylation; carcinogenic factor; chronic inflammation; eradication; methylation burden