{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:55:25Z","timestamp":1790488525382,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T00:00:00Z","timestamp":1491177600000},"content-version":"vor","delay-in-days":33,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"A National Cancer Center Research and Development Fund, Japan","award":["26-A-15"],"award-info":[{"award-number":["26-A-15"]}]},{"name":"Grants-in-Aid for the Third-Term Comprehensive Cancer Control Strategy from the Ministry of Health, Labour and Welfare, Japan","award":["H22-002"],"award-info":[{"award-number":["H22-002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:p>Aberrant <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> 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 <jats:italic>Helicobacter pylori<\/jats:italic> (<jats:italic>H<\/jats:italic>.\u00a0<jats:italic>pylori<\/jats:italic>)\u2010induced gastritis, we aimed to clarify the impact of the degree of exposure on methylation burden in normal gastric tissues. <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation levels of four CpG islands, <jats:styled-content style=\"fixed-case\">HE<\/jats:styled-content>6, <jats:styled-content style=\"fixed-case\">SA<\/jats:styled-content>9, <jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>5, and <jats:styled-content style=\"fixed-case\">SD<\/jats:styled-content>2, increased by <jats:italic>H<\/jats:italic>.\u00a0<jats:italic>pylori<\/jats:italic> infection, depending upon the infection period. After eradication of <jats:italic>H<\/jats:italic>.\u00a0<jats:italic>pylori<\/jats:italic>,<jats:styled-content style=\"fixed-case\"> DNA<\/jats:styled-content> methylation levels decreased, but tended to be higher in gastric mucosae with a longer infection period. <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> molecules with dense methylation, but not those with sparse methylation, increased depending upon the infection period. <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation levels of one of the four CpG islands, <jats:styled-content style=\"fixed-case\">SA<\/jats:styled-content>9, tended to be higher in gastric mucosae of gerbils infected with <jats:italic>H<\/jats:italic>.\u00a0<jats:italic>pylori<\/jats:italic>, even 50\u00a0weeks after eradication than in those of non\u2010infected 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.<\/jats:p>","DOI":"10.1111\/cas.13136","type":"journal-article","created":{"date-parts":[[2016,12,20]],"date-time":"2016-12-20T00:12:57Z","timestamp":1482192777000},"page":"316-321","source":"Crossref","is-referenced-by-count":15,"title":["Degree of methylation burden is determined by the exposure period to carcinogenic factors"],"prefix":"10.1111","volume":"108","author":[{"given":"Hideyuki","family":"Takeshima","sequence":"first","affiliation":[{"name":"Division of Epigenomics National Cancer Center Research Institute Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Niwa","sequence":"additional","affiliation":[{"name":"Division of Epigenomics National Cancer Center Research Institute Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Toyoda","sequence":"additional","affiliation":[{"name":"Division of Pathology National Institute of Health Sciences Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Wakabayashi","sequence":"additional","affiliation":[{"name":"Division of Epigenomics National Cancer Center Research Institute Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Division of Epigenomics National Cancer Center Research Institute Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikazu","family":"Ushijima","sequence":"additional","affiliation":[{"name":"Division of Epigenomics National Cancer Center Research Institute Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,4,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3130"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.07.020"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2013.00258"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1571"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-06-0436"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-307094"},{"key":"e_1_2_7_8_1","first-page":"269","volume-title":"Epigenetic Epidemiology","author":"Ushijima T","year":"2011"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24394"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5547"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgq219"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-2755"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/35006081"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-010-0918-4"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.2217\/epi.13.7"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.26072"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(84)90592-4"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/hel.12243"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2005.00030.x"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.093310.109"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2014.11.038"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.241"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24018"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10120-011-0126-1"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2007.40.2.142"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205153"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-3690"},{"key":"e_1_2_7_28_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1158\/0008-5472.11.65.1","article-title":"Decreased fidelity in replicating CpG methylation patterns in cancer cells","volume":"65","author":"Ushijima T","year":"2005","journal-title":"Cancer Res"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12750"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcas.13136","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.13136","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T01:15:17Z","timestamp":1695863717000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.13136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,3]]}},"alternative-id":["10.1111\/cas.13136"],"URL":"https:\/\/doi.org\/10.1111\/cas.13136","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3]]}}}