Risk assessment of pulmonary diseases caused by fibers and particlesusing nitrative DNA lesion as a potential biomarker

• Project/Area Number: 19590585
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hygiene
• Research Institution: Mie University
• Principal Investigator: HIRAKU Yusuke Mie University, 大学院・医学系研究科, 講師 (30324510)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 繊維 / 粒子状物質 / アスベスト / リスク評価 / 発がん / 慢性炎症 / 活性酸素 / 窒素種 / DNA 損傷 / 8-ニトログアニン / 繊維・粒子状物質 / 活性酸素・窒素種 / DNA損傷

Research Abstract

繊維・粒子状物質による発がんなどの呼吸器疾患には、慢性炎症が重要な役割を果たすと考えられる。8-ニトログアニンとは、炎症条件下で生成される変異誘発性DNA損傷塩基である。我々はアスベストを気管内投与したマウスの気道上皮で8-ニトログアニンが生成され、アスベストの発がん性の強さを反映するという注目すべき知見を得た。また感染・炎症関連発がん患者の臨床検体を用いた研究から、8-ニトログアニン生成は慢性炎症からがんの発生・進展に至る過程を反映し、発がんリスクを評価するバイオマーカーとして応用可能であることを明らかにした。

Research Products

• [Journal Article] Themechanisms of oxidative DNA damage andapoptosis induced by norsalsolinol, anendogenous tetrahydroisoquinoline derivativeassociated with Parkinson's disease (2009)
  • Author(s): Kobayashi H, Hiraku Y (他5名)
  • Journal Title: J.Neurochem 108 Pages: 397-407
  • Peer Reviewed
• [Journal Article] The mechanisms of oxidative DNA damage and apoptosis induced by norsalsolinol, an endogenous tetrahydroisoquinoline derivative associated with Parkinson's disease (2009)
  • Author(s): Kobayashi, H., et al.
  • Journal Title: J. Neurochem. 108 Pages: 397-407
  • Peer Reviewed
• [Journal Article] Urinary8-oxo-7,8-dihydro-2'-deoxyguanosine in patientswith parasite infection and effect ofantiparasitic drug in relation to cholangiocarcinogenesis (2008)
  • Author(s): Thanan R, Hiraku Y (他8名)
  • Journal Title: Cancer Epidemiol. Biomarkers. Prev 17 Pages: 518-524
  • Peer Reviewed
• [Journal Article] Oxidativeand nitrative stress in Opisthorchis viverriniinfected hamsters: an indirect effect afterpraziquantel treatment (2008)
  • Author(s): Pinlaor S, Hiraku Y (他9名)
  • Journal Title: Am. J. Trop. Med. Hyg 78 Pages: 564-573
  • Peer Reviewed
• [Journal Article] Reactivenitrogen species-dependent DNA damage in EBV-associated nasopharyngeal carcinoma : The relation to STAT3 activation and EGFRexpression (2008)
  • Author(s): Ma N, Hiraku Y (他8名)
  • Journal Title: Int. J. Cancer 122 Pages: 2517-2525
  • Peer Reviewed
• [Journal Article] Mechanism of UVA-dependent DNA damageinduced by an antitumor drug dacarbazine inrelation to its photogenotoxicity (2008)
  • Author(s): Iwamoto T, Hiraku Y, Okuda M, Kawanishi S
  • Journal Title: Pharm. Res 25 Pages: 598-604
  • Peer Reviewed
• [Journal Article] Reactive nitrogen species-dependent DNA damage in EBV-associated nasopharyngeal carcinoma : The relation to STAT3 activation and EGFR expression (2008)
  • Author(s): Ma, N., al.
  • Journal Title: Int. J. Cancer 122 Pages: 2517-2525
  • Peer Reviewed
• [Journal Article] Oxidative and nitrative stress in Opisthorchis viverrini-infectedhamsters : an indirect effect after praziquantel treatment (2008)
  • Author(s): Pinlaor, S., et al.
  • Journal Title: Am. J. Trop. Med. Hyg 78 Pages: 564-573
  • Peer Reviewed
• [Journal Article] Urinary 8-oxo-7, 8-dihydro-2'-deoxyguanosine in patients with parasite infection and effect of antiparasitic drug in relation to cholangiocarcinogenesis (2008)
  • Author(s): Thanan, R., et al.
  • Journal Title: Cancer Epidemiol. Biomarkers. Prev. 17 Pages: 518-524
  • Peer Reviewed
• [Journal Article] Mechanism of UVA-dependent DNA damage induced by an antitumor drug dacarbazine in relation to its photogenotoxicity (2008)
  • Author(s): Iwamoto, T., et al.
  • Journal Title: Pharm. Res. 25 Pages: 598-604
  • Peer Reviewed
• [Journal Article] Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosineininfection and the effect ofanti-parasiticcholangiocarcinogenesis (2008)
  • Author(s): Thanan, R, et. al.
  • Journal Title: Cancer Epidemiol.Biomarkers Prev. 17 Pages: 518-524
  • Peer Reviewed
• [Journal Article] Mechanism of UVA-dependent DNA damage induced by an antitumor drugdacarbazine in relation to its photogenotoxicity (2008)
  • Author(s): Iwamoto, T, et. al.
  • Journal Title: Pharm.Res. 25 Pages: 598-604
  • Peer Reviewed
• [Journal Article] Oxidative and nitrative stress caused bysubcutaneous implantation of a foreign bodyaccelerates sarcoma development in Trp53+/-mice (2007)
  • Author(s): Tazawa H, Hiraku Y (他8名)
  • Journal Title: Carcinogenesis 28 Pages: 191-198
  • Peer Reviewed
• [Journal Article] PhotosensitizedDNA damage induced by NADH:site specificity and mechanism (2007)
  • Author(s): Ito K, Hiraku Y, Kawanishi S
  • Journal Title: Free Radic. Res 41 Pages: 461-468
  • Peer Reviewed
• [Journal Article] PhotosensitizedDNA damage induced by NADH8-Nitroguanine as a potential biomarker forprogression of malignant fibrous histiocytoma,a model of inflammation-related cancer (2007)
  • Author(s): Hoki Y, Hiraku Y (他5名)
  • Journal Title: Oncol. Rep 18 Pages: 1165-1169
  • Peer Reviewed
• [Journal Article] iNOSdependentDNA damage in patients with malignant fibrous histiocytoma in relation to prognosis (2007)
  • Author(s): Hoki Y, Hiraku Y (他7名)
  • Journal Title: Cancer Sci 98 Pages: 163-168
  • Peer Reviewed
• [Journal Article] Nitrativeand oxidative DNA damage in cervicalintraepithelial neoplasia associated withhuman papilloma virus infection (2007)
  • Author(s): Hiraku Y, Tabata T (他4名)
  • Journal Title: Cancer Sci. 98 Pages: 964-972
  • Peer Reviewed
• [Journal Article] Photosensitized DNA damage and itsprotection via a novel mechanism (2007)
  • Author(s): Hiraku Y, Ito K, Hirakawa K, Kawanishi S
  • Journal Title: Photochem. Photobiol 83 Pages: 205-212
  • Peer Reviewed
• [Journal Article] 9-Nitroanthracene derivative as a precursor of anthraquinone for photodynamic therapy (2007)
  • Author(s): Fukuhara K, Hiraku Y(他8名)
  • Journal Title: Bioorg. Med. Chem 15 Pages: 3869-3873
  • Peer Reviewed
• [Journal Article] Nitrative and oxidative DNA damage in cervical intraepithelial neoplasiaassociated with human papilloma virus infection, (2007)
  • Author(s): Hiraku, Y, et. al.
  • Journal Title: Cancer Sci. 98 Pages: 964-972
  • Peer Reviewed
• [Journal Article] Photosensitized DNA damage and its protection via a novel mechanism (2007)
  • Author(s): Hiraku, Y, et. al.
  • Journal Title: Photochem.Photobiol. 83 Pages: 205-212
  • Peer Reviewed
• [Journal Article] iNOS-dependent DNA damage in patients with malignant fibrous histiocytomain relation to prognosis (2007)
  • Author(s): Hoki, Y, et. al.
  • Journal Title: Cancer Sci. 98 Pages: 163-168
  • Peer Reviewed
• [Journal Article] 8-Nitroguanine as a potential biomarker for progression of malignant fibroushistiocytoma,a model of inflammation-related cancer (2007)
  • Author(s): Hoki, Y, et. al.
  • Journal Title: Oncol.Rep. 18 Pages: 1165-1169
  • Peer Reviewed
• [Journal Article] Oxidative and nitrative stress caused by subcutaneous implantation of a foreignbody accelerates sarcoma develoment in Trp53^<+/-> mice (2007)
  • Author(s): Tazawa, H, et. al.
  • Journal Title: Carcinogenesis 28 Pages: 191-198
  • Peer Reviewed
• [Journal Article] Photosensitized DNA damage induced by NADH:site specificity andmechanism (2007)
  • Author(s): Ito, K, et. al.
  • Journal Title: Free Radic.Res. 41 Pages: 461-468
  • Peer Reviewed
• [Journal Article] 9-Nitroanthracene derivative as ap recursor of anthraquinone for photodynamictherapy (2007)
  • Author(s): Fukuhara, K, et. al.
  • Journal Title: Bioorg.Med.Chem. 15 Pages: 3869-3873
  • Peer Reviewed
• [Journal Article] Time profiles of the expression of metalloproteinases, tissue inhibitors of metalloproteases, cytokines and collagen in hamsters infectedwith Opisthorchis viverrini with specialreference to peribiliary fibrosis and liverinjury
  • Author(s): Prakobwong, S., Hiraku, Y(他4名)
  • Journal Title: Int. J. Parasitol (印刷中)
  • Peer Reviewed
• [Journal Article] Curcumin reduces oxidative and nitrativeDNA damage through balancing of oxidantantioxidantstatus in hamsters infected with Opisthorchis viverrini
  • Author(s): Pinlaor S, Hiraku Y(他5名)
  • Journal Title: Mol. Nutr. Food Res (印刷中)
  • Peer Reviewed
• [Journal Article] Proteomic identification of carbonylatedproteins in the monkey hippocampus afterischemia-reperfusion
  • Author(s): Oikawa S, Hiraku Y (他8名)
  • Journal Title: Free Radic. Biol. Med (印刷中)
  • Peer Reviewed
• [Journal Article] Curcumin reduces oxidative and nitrative DNA damage through balancing of oxidant-antioxidant status in hamsters infected with Opisthorchis viverrini
  • Author(s): Pinlaor, S., et al.
  • Journal Title: Mol. Nutr. Food Res. (印刷中)
  • Peer Reviewed
• [Journal Article] Time profiles of the expression of metalloproteinases, tissue inhibitors of metalloproteases, cytokines and collagen in hamsters infected with Opisthorchis viverrini with special reference to peribiliary fibrosis and liver injury
  • Author(s): Prakobwong, S., et al.
  • Journal Title: Int. J. Parasitol. (印刷中)
  • Peer Reviewed
• [Journal Article] Proteomic identification of carbonylated proteins in the monkey hippocampus after ischemia-reperfusion
  • Author(s): Oikawa, S., et al.
  • Journal Title: Free Radic. Biol. Med. (印刷中)
  • Peer Reviewed
• [Journal Article] Reactive nitrogen species-dependent DNA damage in EBV-associatednasopharyngeal carcinoma:the relation to STAT3 activation and EGFR・expression
  • Author(s): Ma, N, et. al.
  • Journal Title: Int.J.Cancer (印刷中)
  • Peer Reviewed
• [Journal Article] Oxidative and nitrative stress in Opisthorchis viverrini-infected hamsters:anindirect effect after praziquantel treatment
  • Author(s): Pinlaor, S, et. al.
  • Journal Title: Am.J.Trop.Med.Hyg. (印刷中)
  • Peer Reviewed
• [Journal Article] Role of matrix metalloproteinase(MMP)-2 and MMP-9in the pathogenesis ofhamster opisthorchiasis:effect ofn raziauantel treatment
  • Author(s): Prakobwong, S, et. al.
  • Journal Title: Southeast Asian J.Trop. Med.Public Health (印刷中)
  • Peer Reviewed
• [Presentation] 奨励賞受賞講演「感染・炎症関連発がんにおけるDNA損傷塩基8-ニトログアニンの生成とその意義」 (2009)
  • Author(s): 平工雄介
  • Organizer: 第79回日本衛生学会総会
  • Place of Presentation: 東京都港区
  • Year and Date: 2009-03-31
• [Presentation] 感染・炎症関連発がんにおけるDNA損傷塩基8-ニトログアニンの生成とその意義、奨励賞受賞講演 (2009)
  • Author(s): 平工雄介
  • Organizer: 第79回日本衛生学会総会、東京
  • Place of Presentation: 東京
  • Year and Date: 2009-03-29
• [Presentation] Metal-mediated DNA damage induced by methylene blue in relation to the carcinogenicity (メチレンブルーによる金属依存性DNA損傷:発がん性との関連) (2008)
  • Author(s): 平工雄介
  • Organizer: 日本環境変異原学会第37回大会
  • Place of Presentation: 沖縄県宜野湾市
  • Year and Date: 2008-12-04
• [Presentation] Formation of 8-nitroguanine, a nitrative DNA lesion, in patients with EBV-associated nasopharyngeal carcinoma (EBウイルス感染による上咽頭癌患者におけるニトロ化DNA損傷塩基8-ニトログアニンの生成) (2008)
  • Author(s): 平工雄介
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 2008-10-29
• [Presentation] アスベスト曝露マウス肺におけるDNA損傷塩基8-ニトログアニンの生成(第2報)免疫組織化学法における染色性の定量的解析 (2008)
  • Author(s): 平工雄介
  • Organizer: 第81回日本産業衛生学会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2008-06-27
• [Presentation] EBウイルス感染による上咽頭癌患者におけるニトロ化DNA損傷 (2008)
  • Author(s): 平工雄介
  • Organizer: 第8回日本NO学会学術集会
  • Place of Presentation: 宮城県仙台市
  • Year and Date: 2008-05-09
• [Presentation] シンポジウム「分子予防・環境医学への新たな挑戦」感染・炎症関連発がんにおけるニトロ化DNA損傷塩基8-ニトログアニンの役割 (2008)
  • Author(s): 平工 雄介
  • Organizer: 第78回日本衛生学会総会
  • Place of Presentation: 熊本県熊本市
  • Year and Date: 2008-03-30
• [Presentation] Metal-mediated DNA damageinduced by methylene blue in relation to thecarcinogenicity(メチレンブルーによる金属依存性DNA 損傷:発がん性との関連) (2008)
  • Author(s): 平工雄介, 他
  • Organizer: 日本環境変異原学会第37回大会
  • Place of Presentation: 宜野湾
• [Presentation] Formation of 8-nitroguanine, anitrative DNA lesion, in patients with EBVassociatednaso-pharyngeal carcinoma(EBウイルス感染による上咽頭癌患者におけるニトロ化DNA損傷塩基8-ニトログアニンの生成) (2008)
  • Author(s): 平工雄介, 他
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] Formation of 8-nitroguanine, a nitrative DNA lesion, inpatients infected with oncogenic viruses, HPV and EBV (2008)
  • Author(s): Yusuke Hiraku, 他
  • Organizer: The 5th International Conference onthe Biology, Chemistry and TherapeuticApplications of Nitric Oxide
  • Place of Presentation: Bregenz, Austria
• [Presentation] アスベスト曝露マウス肺におけるDNA 損傷塩基8-ニトログアニンの生成(第2報)免疫組織化学法における染色性の定量的解析 (2008)
  • Author(s): 平工雄介, 村田真理子
  • Organizer: 第81回日本産業衛生学会
  • Place of Presentation: 札幌
• [Presentation] EB ウイルス感染による上咽頭癌患者におけるニトロ化DNA損傷 (2008)
  • Author(s): 平工雄介, 他
  • Organizer: 第8回日本NO学会学術集会
  • Place of Presentation: 仙台
• [Presentation] シンポジウム「分子予防・環境医学への新たな挑戦」感染・炎症関連発がんにおけるニトロ化DNA損傷塩基8-ニトログアニンの役割 (2008)
  • Author(s): 平工雄介, 川西正祐
  • Organizer: 第78回日本衛生学会総会
  • Place of Presentation: 熊本
• [Presentation] Formation of 8-nitroguanine, a nitrative DNA lesion, in patients infected with oncogenic viruses, HPV and EBV (2008)
  • Author(s): Yusuke Hiraku
  • Organizer: The 5th International Conference on the Biology, Chemistry and Therapeutic Applications of Nitric Oxide
  • Place of Presentation: Bregenz, Austria
• [Presentation] Formation of 8-nitroguanine,a nitrative DNA lesion,in the lung of miceexposed to asbestos(アスベスト曝露マウス肺におけるニトロ化DNA損傷塩基8-ニトログアニンの生成) (2007)
  • Author(s): 平工 雄介
  • Organizer: 第1回アジア環境変異原学会・日本環境変異原学会第36回大会
  • Place of Presentation: 福岡県北九州市
  • Year and Date: 2007-11-30
• [Presentation] アスベスト気管内投与マウスの肺組織におけるDNA 損傷塩基8-ニトログアニンの生成 (2007)
  • Author(s): 平工雄介, 他
  • Organizer: 日本産業衛生学会東海地方会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-11-17
• [Presentation] アスベスト気管内投与マウスの肺組織におけるDNA損傷塩基8-ニトログアニンの生成 (2007)
  • Author(s): 平工 雄介
  • Organizer: 平成19年度日本産業衛生学会東海地方会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 2007-11-17
• [Presentation] アスベスト気管内投与マウスの肺組織におけるニトロ化DNA損傷 (2007)
  • Author(s): 平工 雄介
  • Organizer: 第7回分子予防環境医学研究会
  • Place of Presentation: 福岡県北九州市
  • Year and Date: 2007-10-27
• [Presentation] Nitrative DNA damageinthelungofasbestos-exposedmice(アスベスト曝露マウス肺におけるニトロ化DNA損傷) (2007)
  • Author(s): 平工 雄介
  • Organizer: 第66回目本癌学会総会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2007-10-03
• [Presentation] LPSによるニトコ化DNA損傷の分子機構:感染・炎症関連発がんとの関連 (2007)
  • Author(s): 平工 雄介
  • Organizer: 第7回日本NO学会学術集会
  • Place of Presentation: 滋賀県大津市
  • Year and Date: 2007-05-17
• [Presentation] アスベスト曝露マウス肺におけるDNA損傷塩基8-ニトログアニンの生成 (2007)
  • Author(s): 平工 雄介
  • Organizer: 第80回日本産業衛生学会
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 2007-04-27
• [Presentation] Formation of 8-nitroguanine, anitrative DNA lesion, in the lung of miceexposed to asbestos(アスベスト曝露マウス肺におけるニトロ化DNA 損傷塩基8-ニトログアニンの生成) (2007)
  • Author(s): 平工雄介, 他
  • Organizer: 第1回アジア環境変異原学会・日本環境変異原学会第36回大会
  • Place of Presentation: 北九州
• [Presentation] アスベスト気管内投与マウスの肺組織におけるニトロ化DNA損傷 (2007)
  • Author(s): 平工雄介, 他
  • Organizer: 第7回分子予防環境医学研究会
  • Place of Presentation: 北九州
• [Presentation] Nitrative DNA damage in thelung of asbestos-exposed mice(アスベスト曝露マウス肺におけるニトロ化DNA 損傷) (2007)
  • Author(s): 平工雄介, 他
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] LPS によるニトロ化DNA損傷の分子機構 : 感染・炎症関連発がんとの関連 (2007)
  • Author(s): 平工雄介, 他
  • Organizer: 第7回日本NO学会学術集会
  • Place of Presentation: 大津
• [Presentation] アスベスト曝露マウス肺におけるDNA 損傷塩基8-ニトログアニンの生成 (2007)
  • Author(s): 平工雄介, 他
  • Organizer: 第80回日本産業衛生学会
  • Place of Presentation: 大阪
• [Book] 活性酸素・窒素種とDNA 損傷、化学フロンティア18ゲノム化学(齋藤烈、杉山弘、中谷和彦編) (2007)
  • Author(s): 平工雄介、川西正祐
  • Publisher: 化学同人
• [Book] 化学フロンティア18ゲノム化学(齋藤烈、杉山弘、中谷和彦編) (2007)
  • Author(s): 平工 雄介、川西 正祐
  • Publisher: 化学同人
• [Book] Immunohistochemicalanalysis of 8-nitroguanine, a nitrative DNA lesion, in relation to inflammation-associatedcarcinogenesis, In: Inflammation and Cancer-Methods and Protocols: Volume 2, MolecularAnalysis and Pathways(Kozlov SV(ed.))
  • Author(s): Hiraku Y, Kawanishi S
  • Publisher: Humana Press, New York, NY, USAUSA (印刷中)
• [Book] Inflammation and Cancer-Methods and Protocols : Volume 2, Molecular Analysis and Pathways, Kozlov, S. V. (Ed. )
  • Author(s): Hiraku, Y., Kawanishi, S.
  • Publisher: Humana Press, New York, NY, USA(印刷中)
• [Remarks]
  • URL: http://www.medic.mie-u.ac.jp/eiseigaku/