Elucidation of the development mechanism of the alcohol and aceta l dehyde-induced squamous-cell-carcinoma by using A/dh2 deficient mice.

• Project/Area Number: 20590620
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hygiene
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: OZAKI Shinichi 産業医科大学, 医学部, 非常勤助教 (70412632)
• Co-Investigator(Kenkyū-buntansha): OYAMA Tsunehiro 兵庫医科大学, 医学部, 非常勤講師 (00309965) ; KAWAMOTO Toshihiro 産業医科大学, 医学部, 教授 (60177748) ; GOTOH Akinobu 兵庫医科大学, 医学部, 教授 (70283885) ; ISSE Toyohi 産業医科大学, 医学部, 准教授 (80341494)
• Project Period (FY): 2008 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 環境中毒 / Aldh2欠損マウス / 癌 / アルコール / 皮膚癌 / 扁平上皮癌

Research Abstract

The outer skin can be observed simply. Therefore we administered acetaldehyde to the Aldh2-deficient mice subcutaneously. Squamous cell carcinomas occurred on the back skins of the Aldh2--deficient mice and we examined them molecular biologically and pathologically.
It is well known that the Aldh2-deficient individuals should have greater risks of the incidence of the oropharyngeal or the esophageal cancer by drinking.
We apply this result to the medical treatment and the prevention of cancers.

Research Products

• [Journal Article] Cytochrome P450 in non-small cell lung cancer related to exogenous chemical metabolism (2012)
  • Author(s): Oyama T, Uramoto H, Kagawa N, Yoshimatsu T, Osaki T, Nakanishi R, Nagaya H, Kaneko K, Muto M, KawamotoT, Tanaka F, Gotoh A
  • Journal Title: Front Biosci Volume: S4 Pages: 1539-1546
  • Peer Reviewed
• [Journal Article] The effect of ethanol on the formation of N^<2-> ethylidene-dG adducts in mice: implications for alcohol-related carcinogenicity of the oral cavity and esophagus (2012)
  • Author(s): Yu H-S, Oyama T, Matsuda T, Isse T, Yamaguchi T, Tanaka M, Tsuji M, Kawamoto T
  • Journal Title: Biomarkers Volume: 17 Issue: 3 Pages: 269-274
  • DOI: 10.3109/1354750x.2012.666675
  • Peer Reviewed
• [Journal Article] Cytochrome P450 in non-small cell lung cancer related to exogenous chemical metabolism. (2012)
  • Author(s): Oyama T
  • Journal Title: Front Biosci Volume: S4 Pages: 1539-1546
  • Peer Reviewed
• [Journal Article] Molecular diagnosis of MACCI status in lung adenocarcinoma by immunohistochemical analysis (2011)
  • Author(s): Gu CD, Uramoto H, Onitsuka T, Shimokawa H, Iwanami T, Nakagawa M, Oyanla T, Tanaka F
  • Journal Title: Anti cancer Res Volume: 31 Pages: 1141-1146
  • Peer Reviewed
• [Journal Article] TS gene tandem repeats in esophageal cancer patients receiving chemoradiotherapy (2011)
  • Author(s): Kaneko K, et al
  • Journal Title: Front Biosci Volume: 16 Issue: 1 Pages: 1036-1043
  • DOI: 10.2741/3733
  • Peer Reviewed
• [Journal Article] Molecular diagnosis of MACC1 status in lung adenocarcinoma by immunohistochemical analysis (2011)
  • Author(s): Gu CD, et al
  • Journal Title: Anticancer Res Volume: 31 Pages: 1141-1146
  • Peer Reviewed
• [Journal Article] Reduced bone formation in alcohol-induced osteopenia is associated with elevated p21 expression in bone marrow cells in aldehyde dehydrogenase 2-disrupted mice (2011)
  • Author(s): Shimizu Y, et al
  • Journal Title: Bone Volume: 48 Issue: 5 Pages: 1075-1086
  • DOI: 10.1016/j.bone.2011.01.008
  • Peer Reviewed
• [Journal Article] Effects of acetaldehyde inhalation in mitochondrial aldehyde dehydrogenase deficient mice (Aldh2^<-/->) (2010)
  • Author(s): Oyama T, Nagayoshi H, Matsuda T, Oka M, Isse T, Yu HS, Pham TTP, Tanaka M, Kagawa N, Kaneko K, Kawamoto T
  • Journal Title: Front Biosci (Elite Ed) Volume: 2 Pages: 1344-1354
  • Peer Reviewed
• [Journal Article] Effects of acetaldehyde inhalation in mitochondrial aldehyde dehydrogenase deficient mice (Aldh2^<-/->). (2010)
  • Author(s): Oyama T, Nagayoshi H, Matsuda T, Oka M, Isse T, Yu HS, Pham TTP, Tanaka M, Kagawa N, Kaneko K, Kawamoto T
  • Journal Title: Front Biosci (Elite Ed) 2 Pages: 1344-1354
  • Peer Reviewed
• [Journal Article] EGFR gene alterations as a prognostic biomarker in advanced esophageal squamous cell carcinoma. (2010)
  • Author(s): Kaneko K, Kumekawa Y, Makino R, Nozawa H, Hirayama Y, Kogo M, Konishi K, Katagiri A, Kubota Y, Muramoto T, Kushima M, Ohmori T, Oyama T, Kagawa N, Ohtsu A, Imawari M
  • Journal Title: Front Biosci 15 Pages: 65-72
  • Peer Reviewed
• [Journal Article] Effects of acetaldehyde inhalation in mitochondrial aldehyde dehydrogenase deficient mice (Aldh2^-) (2010)
  • Author(s): Oyama T, et al.
  • Journal Title: Front Biosci Volume: 2 Pages: 1344-1354
  • Peer Reviewed
• [Journal Article] Comprehensive molecular analyses of lung adenocarcinoma with regard to the EGFR, K-ras, MET, and HGF status. (2010)
  • Author(s): Onitsuka T, et al.
  • Journal Title: J Thorac Oncol Volume: 5 Pages: 591-596
  • Peer Reviewed
• [Journal Article] EGFR gene alterations as a prognostic biomarker in advanced esophageal squamous cell carcinoma. (2010)
  • Author(s): Kaneko K, et al
  • Journal Title: Front Biosci Volume: 15 Pages: 65-72
  • Peer Reviewed
• [Journal Article] Expression of aromatase CYP19 and its relationship with parameters in NSCLC (2009)
  • Author(s): Oyama T, Kagawa N, Sugio K, Uramoto H, Hatano O, Harada N, Kanako K, Kawamoto T, Yasumoto K
  • Journal Title: Front Biosci Volume: 14 Pages: 2285-2292
  • Peer Reviewed
• [Journal Article] Expression of aromatase CYP19 and its relationship with parameters in NSCLC. (2009)
  • Author(s): Oyama T, Kagawa N, Sugio K, Uramoto H, Hatano O, Harada N, Kanako K, Kawamoto T, Yasumoto K
  • Journal Title: Front Biosci 14 Pages: 2285-2292
  • Peer Reviewed
• [Journal Article] Association between estrogen receptor beta expression and epidermal growth factor receptor mutation in the postoperative prognosis of patients with adenocarcinoma of the lung. (2009)
  • Author(s): Nose N, Sugio K, Oyama T, Nozoe N, Uramoto H, Iwata T, Onitsuka T, Yasumoto K
  • Journal Title: J Clin Oncol 27 Pages: 411-417
  • Peer Reviewed
• [Journal Article] The onset of angiogenesis in a multistep process of esophageal squamous cell carcinoma. (2009)
  • Author(s): Kubota Y, et al.
  • Journal Title: Front Biosci 14 Pages: 3872-3878
  • Peer Reviewed
• [Journal Article] Association between estrogen receptor beta expression and epidermal growth factor receptor mutation in the postoperative prognosis of patients with adenocarcinoma of the lung. (2009)
  • Author(s): Nose N, et al.
  • Journal Title: J Clin Oncol 27 Pages: 411-417
  • Peer Reviewed
• [Journal Article] Expression of aromatase CYP19 and its relationship with parameters in NSCLC. (2009)
  • Author(s): Oyama T, et al.
  • Journal Title: Front Biosci 14 Pages: 2285-2292
  • Peer Reviewed
• [Journal Article] Effects of 5-week ethanol feeding on the liver of 5-week ethanol feeding on the liver of aldehyde dehydrogenase 2 knockout mice. (2008)
  • Author(s): Matsumoto A, Kawamoto T, Mutoh F, Isse T, Oyama T, Kitagawa K, Nakayama KI, Ichiba M
  • Journal Title: Pharmacogenet Genom Volume: 18 Issue: 10 Pages: 847-852
  • DOI: 10.1097/fpc.0b013e328307a0a9
  • Peer Reviewed
• [Journal Article] Increased frequencies of micronucleated reticulocytes and T-cell receptor mutation in A ldh2 knockout mice exposed to acetaldehyde (2008)
  • Author(s): Kunugita N, Isse T, Oyama T, Kitagawa K, Ogawa M, Yamaguchi T, Kinaga T, Kawamoto T
  • Journal Title: J Toxicol Sci Volume: 33 Pages: 31-36
  • Peer Reviewed
• [Journal Article] Expression of Cytochrome P450 in non-small cell lung cancer (2008)
  • Author(s): Oyama T, Sugio K, Isse T, Matsumoto A, Nose N, Uramoto H, Nozoe T, Morita M, Kagawa N, Osaki T, Muto M, Yasumoto K, Kawamoto T
  • Journal Title: Front Biosci Volume: 13 Pages: 5787-5793
  • Peer Reviewed
• [Journal Article] Expression of Cytochrome P450 in non-small cell lung cancer. (2008)
  • Author(s): Oyama T, Sugio K, Isse T, Matsumoto A, Nose N, Uramoto H, Nozoe T, Morita M, Kagawa N, Osaki T, Muto M, Yasumoto K, Kawamoto T
  • Journal Title: Front Biosci 13 Pages: 5787-5793
  • Peer Reviewed
• [Journal Article] Effects of 5-week ethanol feeding on the liver of aldehyde dehydrogenase 2 knockout mice. (2008)
  • Author(s): Matsumoto A, et al.
  • Journal Title: Pharmacogenet Genom 18 Pages: 847-852
  • Peer Reviewed
• [Journal Article] Increased frequencies of micronucleated reticulocytes and T-cell receptor mutation in Aldh2 knockout mice exposed to acetaldehyde. (2008)
  • Author(s): Kunugita N, et al.
  • Journal Title: J Toxicol Sci 33 Pages: 31-36
  • Peer Reviewed
• [Journal Article] Expression of Cytochrome P450 in non-small cell lung cancer. (2008)
  • Author(s): Oyama T, et al.
  • Journal Title: Front Biosci 13 Pages: 5783-5793
  • Peer Reviewed
• [Presentation] Cytochrome P450(CYP) and p53 immunoreactivity in breast cancer (2012)
  • Author(s): 小山倫浩、浦本秀隆、下川秀彦、宗知子、花桐武志、宗哲哉、吉松隆、長屋寿雄、大崎敏弘、中西良一、後藤章暢、田中文啓、安元公正
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-19
• [Presentation] Cytochrome P450 (CYP) and p53 immunoreactivity in breast cancer. (2012)
  • Author(s): 小山倫浩
  • Organizer: 第71回 日本癌学会学術総会
  • Place of Presentation: ロイトン札幌、さっぽろ芸文館、札幌市教育文化会館（札幌）
  • Invited
• [Presentation] The survivals and body weight variations of aldehyde dehydrogenase 2 knockout mice treated with ethanol (2011)
  • Author(s): 小山倫浩、余旭勝、辻真弓、田中政幸、松田知成、浦本秀隆、田中文啓、川本俊弘
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] The survivals and body weight variations of aldehyde dehydrogenase 2 knockout mice treated with ethanol (2011)
  • Author(s): 小山倫浩
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)(招待講演)
  • Year and Date: 2011-10-03
• [Presentation] N^<-2-> ethylidene-dG DNA adducts in organs of Aldh2 knockout mice treated with acetaldehyde inhalation (2010)
  • Author(s): 小山倫浩,Pham Thi-Thu-Phoung,余旭勝,田中政幸、永吉晴奈、松田知成、川本俊弘
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] N^<2->ethylidene-dG DNA adducts in organs of Aldh2 knockout mice treated with acetaldehyde inhalation. (2010)
  • Author(s): 小山倫浩, Pham Thi-Thu-Phoung, 余旭勝, 田中政幸、永吉晴奈、松田知成、川本俊弘
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-23
• [Presentation] N^2-ethylidene-dG DNA adducts in organs of Aldh2 knockout mice treated with acetaldehyde inhalation (2010)
  • Author(s): 小山倫浩
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-09-23
• [Presentation] N^<-2-> ethyl-2'-deoxyguanosine DNA adducts in liver and lung of Aldh.2 knockout mice treated with acetaldehyde inhalation (2009)
  • Author(s): 小山倫浩,Pham Thi-Thu-Phoung,余旭勝,田中政幸、永吉晴奈、若松めぐみ,松田知成、川本俊弘
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02
• [Presentation] N^<2->ethyl-2'-deoxyguanosine DNA adducts in liver and lung of Aldh2 knockout mice treated with acetaldehyde inhalation. (2009)
  • Author(s): 小山倫浩, Pham Thi-Thu-Phoung, 余旭勝, 田中政幸、永吉晴奈、若松めぐみ, 松田知成、川本俊弘
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] N^2-ethyl-2' -deoxyguanosine DNA adducts in liver and lung of Aldh2 knockout mice treated with acetaldehyde inhalation. (2009)
  • Author(s): 小山倫浩
  • Organizer: 第68回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] ALDH2ノックアウトマウスを用いたアルコール腹腔内投与による臓器アセトアルデヒド分布とDNAアダクトの検討 (2008)
  • Author(s): 湯河良之、堀貴美子、江副康正、松田知成、小山倫浩、荒井さゆり、武藤学、千葉勉
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-30
• [Presentation] ALDH2ノックアウト(KO)マウスを用いたアルコール腹腔内投与による臓器アセトアルデヒド分布とDNAアダクトの検討 (2008)
  • Author(s): 湯河良之、堀貴美子、江副康正、松田知成、小山倫浩、荒井さゆり、黒沢きよ子、蓼沼克嘉、武藤 学、千葉 勉
  • Organizer: 第62回日本食道学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-12