The investigation of the association between variants of the base excision repair(BER) enzymes and carcinogenesis, and the repair activities of BER enzymes against etheno-DNA adducts

2012 Fiscal Year Final Research Report

• Project/Area Number: 22790378
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: GOTO Masanori 浜松医科大学, 医学部, 特別研究員 (00432203)
• Project Period (FY): 2010 – 2012
• Keywords: 8-ヒドロキシグアニン / MUTYH / エテノアダクト / 塩基除去修復遺伝子 / 大腸がん / 活性酸素種 / 過酸化脂質

Research Abstract

We successfully prepared highly homogeneous human MUTYH recombinant protein, and compared the repair activity of 14 variant proteins with that of the wild -type protein. Several variant proteins showed striking low activity, and their variants may contribute to the development of MUTYH-associated polyposis. To search new substrate of base excision repair enzymes, we prepared 8 enzymes, and examined the repair activity against an oligonucleotide containing etheno-DNA adducts, a lipid peroxidation-derived DNA adducts. The base excision repair enzyme, TDG, had activity that is capable of removing thymine mispaired with etheno-DNA adduct of cytosine or guanine.

Research Products

• [Journal Article] Lipid peroxidation-induced DNA adducts in human gastric mucosa (2012)
  • Author(s): Matsuda T, Tao H, Goto M, Yamada H, Suzuki M, Wu Y, Xiao N, He Q, Guo W, Cai Z, Kurabe N, Ishino K, Matsushima Y, Shinmura K, Konno H, Maekawa M, Wang Y, Sugimura H
  • Journal Title: Carcinogenesis Volume: 34 Pages: 121-127
  • DOI: DOI:10.1093/carcin/bgs327
  • Peer Reviewed
• [Journal Article] Impaired suppressive activities of human MUTYH variant proteins against oxidative mutagenesis (2012)
  • Author(s): Shinmura K, Goto M, Tao H, Matsuura S, Matsuda T, Sugimura H
  • Journal Title: World J Gastroenterol Volume: 18 Pages: 6935-6942
  • DOI: DOI:10.3748/wjg.v18.i47.6935.
  • Peer Reviewed
• [Journal Article] Reduced expression of MUTYH with suppressive activity against mutations caused by 8-hydroxyguanine is a novel predictor of a poor prognosis in human gastric cancer (2011)
  • Author(s): Shinmura K, Goto M, Suzuki M, Tao H, Yamada H, Igarashi H, Matsuura S, Maeda M, Konno H, Matsuda T, Sugimura H
  • Journal Title: J Pathol Volume: 225 Pages: 414-423
  • DOI: DOI:10.1002/path.2953
  • Peer Reviewed
• [Journal Article] Germline alterations in 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, Sugimura H
  • Journal Title: Cancer Sci Volume: 102 Pages: 1782-1788
  • DOI: DOI:10.1111/j.1349-7006.2011.02038.x
  • Peer Reviewed
• [Journal Article] Genetic susceptibility to lung cancer (2011)
  • Author(s): Sugimura H, Tao H, Suzuki M, Mori H, Tsuboi M, Matsuura S, Goto M, Shinmura K, Ozawa T, Tanioka F, Sato N, Matsushima Y, Kageyama S, Funai K, Chou PH, Matsuda T
  • Journal Title: Front Biosci (Schol Ed) Volume: 1 Pages: 1463-1477
  • DOI: DOI:10.2741/237
  • Peer Reviewed
• [Journal Article] Aberrant expression and mutation-inducing activity of AID in human lung cancer (2011)
  • Author(s): Shinmura K, Igarashi H, Goto M, Tao H, Yamada H, Matsuura S, Tajima M, Matsuda T, Yamane A, Funai K, Tanahashi M, Niwa H, Ogawa H, Sugimura H
  • Journal Title: Ann Surg Oncol Volume: 18 Pages: 2084-2092
  • DOI: DOI:10.1245/s10434-011-1568-8
  • Peer Reviewed
• [Journal Article] Three novel NEIL1 promoter polymorphisms in gastric cancer patients (2010)
  • Author(s): Goto M, Shinmura K, Tao H, Tsugane S, Sugimura H
  • Journal Title: World J Gastrointest Oncol Volume: 2 Pages: 117-120
  • DOI: DOI:10.4251/wjgo.v2.i2.117
  • Peer Reviewed
• [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, Y amada H, Tsuneyoshi T, Sugimura H
  • Journal Title: Hum Mutat Volume: 31 Pages: 1861-1874
  • DOI: DOI:10.1002/humu.21363
  • Peer Reviewed
• [Presentation] Germline alterations o the CDH1 gene in familial gastric cancer in the Japaese population (2012)
  • Author(s): Yamada H, Shinmura K, Ito H, Kasami H, Sasaki N, Shima H, Tao H, Goto M, Du C, Tsuneyoshi T, Tanioka F, Sugimura H
  • Organizer: 71th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Sapporo
  • Year and Date: 20120919-21
• [Presentation] 癌における MUTYH の 8-hydroxyguanine 誘発変異抑制活性とその発現レベルの予後予測に関する検討 (2012)
  • Author(s): 新村和也、後藤正憲、椙村春彦
  • Organizer: 第65回日本酸化ストレス学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 20120607-08
• [Presentation] 胃癌における MUTYH の 8-hydroxyguanine 誘発変異抑制活性とその発現レベルの予後予測に関する検討 (2012)
  • Author(s): 新村和也、後藤正憲、鈴木雅也、陶弘、山田英孝、五十嵐久喜、松浦駿、前田松喜、今野弘之、松田知成、椙村春彦
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 20120426-28
• [Presentation] The activity and localization of 14 MUTYH variant proteins found in patients with colorectal polyposis and cancer (2011)
  • Author(s): Goto M, Shinmura K, Nakabeppu Y, Tao H, Yamada H, Tsuneyoshi T, Sugimura H
  • Organizer: 70th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
  • Year and Date: 20111003-05
• [Presentation] Aberrant expression and mutation-inducing activity of AID in human lung cancer (2011)
  • Author(s): Shinmura K, Igarashi H, Goto M, Tao H, Yamada H, Matsuura S, Matsuda T, Ogawa H, Sugimura H
  • Organizer: 70th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
  • Year and Date: 20111003-05
• [Presentation] 大腸ポリポーシスと大腸がんの患者で見つかった 14 種の MUTYH 変異型タンパク質の活性と局在の評価 (2011)
  • Author(s): 後藤正憲、新村和也、中別府雄作、陶弘、山田英孝、常吉俊宏、椙村春彦
  • Organizer: がん予防大会 2011(第18回日本がん予防学会、第34回日本がん疫学分子疫学研究会)
  • Place of Presentation: 京都
  • Year and Date: 20110620-21
• [Presentation] ヒト肺癌における脱アミノ化酵素 AID の異常発現と変異誘導能 (2011)
  • Author(s): 新村和也、五十嵐久喜、後藤正憲、陶弘、山田英孝、松浦駿、小川博、椙村春彦
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20110428-30
• [Presentation] Absence of germline mono-allelic promoter hypermethylation of the CDH1 gene in gastric cancer patients (2010)
  • Author(s): Yamada H, Shinmura K, Mori H, Goto M, Iwaizumi M, Konno H, Kataoka H,Yamada M, Ozawa T, Tsuneyoshi T, Tanioka F, Sugimura H
  • Organizer: 69th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Osaka
  • Year and Date: 20100922-24
• [Presentation] Altered expression and the missense polymorphism of the human base excision repair gene NTH1 in gastric cancer (2010)
  • Author(s): Goto M, Shinmura K, Konno H, Sugimura H
  • Organizer: 101th Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: Washington, DC
  • Year and Date: 20100417-21