adductome analysis of human tissues

2011 Fiscal Year Final Research Report

• Project/Area Number: 22659072
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Human pathology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: SUGIMURA Haruhiko 浜松医科大学, 医学部, 教授 (00196742)
• Project Period (FY): 2010 – 2011
• Keywords: DNA付加体 / adductome / 炎症 / 脂質過酸化物 / 胃がん / 塩基除去修復LC-MS / ゲノム

Research Abstract

High performance liquid chromatography and tandem mass spectrometry disclosed at least 10 lipid peroxidation related modified DNA bases in the DNAs extracted under anti-oxidation condition from human autopsy tissues. Among these 10 DNA adducts, 7 of them, 1, N6-etheno-2'-deoxyadenosine(εdA), butanone-etheno-2'-deoxycytidine(BεdC), butanone-etheno-2'-deoxy-5-methylcytidine(BεmedC), butanoneetheno-2'-deoxyadenosine(BεdA), heptanone-etheno-2'-deoxycytidine(HεdC), heptanone-etheno-2'-deoxyadenosine(HεdA), and heptanone-etheno-2'-deoxyguanosine(HεdG) were quantitated in gastric mucosa, resected for gastric cancer in Japan and China. The profiles of these DNA adducts identified the origin of the tissues(China or Japan), implying adductome profile may reflect environmental exposures of individual settings. We further tested the repair machinery against these modified bases and discovered TDG play s role in repairing some of these adducts.

Research Products

• [Journal Article] Germline alterations of the CDH1 gene in familial gastric cancer in the Japanese population (2011)
  • Author(s): Yamada, H., Shinmura, K., Ito, H., Kasami, M., Sasaki, N., Shima, H., Ikeda, M., Tao, H., Goto, M., Ozawa, T., Tsuneyoshi, T., Tanioka, F., and Sugimura
  • Journal Title: Cancer Sci Volume: 103 Pages: 1782-1788
• [Journal Article] Novel Single Nucleotide Polymorphism of the CYP2A13 gene in Japanese individuals (2011)
  • Author(s): Tamaki, Y., Honda, M., Muroi, Y., Arai, T., Sugimura, H., Matsubara, Y., Kanno, S., Ishikawa, M., Hirasawa, N., and Hiratsuka, M.
  • Journal Title: Drug Metab Pharmacokinet Volume: 26(5) Pages: 544-547
• [Journal Article] Genetic susceptibility to lung cancer (2011)
  • Author(s): Sugimura H, et al.
  • Journal Title: Front Biosci Volume: 3 Pages: 1463-1477
• [Journal Article] Detection of lipid peroxidation-induced DNA adducts caused by 4-oxo-2(E)-nonenal and 4-oxo-2(E)-hexenal in human autopsy tissues (2010)
  • Author(s): Chou, P. H., Kageyama, S., Matsuda, S., Kanemoto, K., Sasada, Y., Oka, M., Shinmura, K., Mori, H., Kawai, K., Kasai, H., Sugimura, H., and Matsuda, T.
  • Journal Title: Chem Res Toxicol Volume: 23(9) Pages: 1442-8
• [Journal Article] Adenine DNA glycosylase activity of 14 Human MutY homolog(MUTYH) variant proteins found in patients with colorectal polyposis and cancer (2010)
  • Author(s): Goto, M., Shinmura, K., Nakabeppu, Y., Tao, H., Yamada, H., Tsuneyoshi, T., and Sugimura, H.
  • Journal Title: Hum Mutat Volume: 31 Pages: E1881-74
• [Journal Article] Identification of 5 novel germline APC mutations and characterization of clinical phenotypes in Japanese patients with classical and attenuated familial adenomatous polyposis (2010)
  • Author(s): Tao, H., Shinmura, K., Yamada, H., Maekawa, M., Osawa, S., Takayanagi, Y., Okamoto, K., Terai, T., Mori, H., Nakamura, T., and Sugimura, H.
  • Journal Title: BMC Res Notes Volume: 3(1) Pages: 305
• [Presentation] 酸化的DNA損傷修復に関わる遺伝子多型とヒト発がん (2011)
  • Author(s): 椙村春彦
  • Organizer: 日本環境変異学会
  • Year and Date: 2011-11-21
• [Presentation] ヒトのcommonながんの遺伝的感受性について (2011)
  • Author(s): 椙村春彦
  • Organizer: 病理の立場から癌研セミナー
  • Place of Presentation: 癌研究会吉田講堂(東京)
  • Year and Date: 2011-08-03
• [Presentation] ヒトがんの原因について北陸 (2011)
  • Author(s): 椙村春彦
  • Organizer: がんプロフェッショナルセミナー
  • Place of Presentation: 金沢大学(金沢)
  • Year and Date: 2011-07-17
• [Book] Glioma : Glioblastoma part 2 in Tumors of Central Nervous System, edt by Hayat, Springer (2011)
  • Author(s): Sugimura H, et al.