Quantification of susceptibility for xenobiotics using humanized CYP1A1 and its polymorphism

• Project/Area Number: 19590599
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hygiene
• Research Institution: Showa University
• Principal Investigator: TATEMICHI Masayuki Showa University, 医学部, 教授 (00318263)
• Co-Investigator(Renkei-kenkyūsha): HATA Harumi 昭和大学, 医学部, 助教 (00396441)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 環境保健 / 遺伝子多型 / 薬物代謝酵素 / 動物モデル / CYP4501A1 / ノックインマウス / 発がん感受性

Research Abstract

ヒト型CYP1A1ならびに、ヒト型CYP1A1の遺伝子多型(exon7 Ile/Val)をノックインしたマウスを作成した。CYP1A1は、多種の化学物質における第一相薬物代謝酵素として最も重要な酵素であるが、ヒトとマウスとの種差がマウスで得られるデータのヒトへの外挿化を困難にしている。このマウスを利用することにより、マウスの実験結果をヒトに外挿化することに極めて重要な情報を得ることができるようになった。

Research Products

• [Journal Article] Impact of inducible nitric oxide synthase on cancer progression (2009)
  • Author(s): Tatemichi M, Ogura T, Esumi H.
  • Journal Title: Eurp. J. Cancer Prev. 18 Pages: 1-8
• [Journal Article] Clinical significance of IgG antibody titer against Helicobacter pylori (2009)
  • Author(s): Tatemichi M, Sasazuki S, Inoue M, Tsugane S.
  • Journal Title: Helicobactor (in press)
• [Journal Article] Impact of inducible nitric oxide synthase gene on tumor progression. (2009)
  • Author(s): Tatemichi M, Ogura T, Esumi H
  • Journal Title: Eur J Cancer Prev. 18 Pages: 1-8
  • Peer Reviewed
• [Journal Article] Different etiological role of Helicobacter pylori (Hp) infection in carcinogenesis between intestinal and diffuse gastric cancers: Epidemiological assessment using IgG titer against Hp surface antigen (2008)
  • Author(s): Tatemichi M, Sasazuki S. Inou M, Tsugane S.
  • Journal Title: Acta Onclogica 47(3) Pages: 360-5
• [Journal Article] Lipopolysaccharide induces aberrant hypermethylation of Hic-1 in mouse embryonic fibroblasts lacking p53 gene (2008)
  • Author(s): Tatemichi M, Hata H, Tazawa H, Nakadate T.
  • Journal Title: Anticancer Res. 28 Pages: 2101-8
• [Journal Article] Increased risk of gastric cancer in Japanese subjects is associated with microsatellite polymorphisms in the heme oxygenase-1 and the inducible nitric oxide synthase gene promoters (2008)
  • Author(s): Sawa T, Mounawar M, Tatemichi M, Gilibert I, Katoh T, Ohshima H.
  • Journal Title: Cancer Lett. 28 ; 269(1) Pages: 78-84
• [Journal Article] Association of morphine-induced antinociception with variations in the 5' flanking and 3' untranslated regions of the mu opioid receptor gene in 10 inbred mouse strains (2008)
  • Author(s): Shigeta Y, Kasai S, Han W, Hata H, et.al.
  • Journal Title: Pharmacogenet Genomics 18 Pages: 927-36
• [Journal Article] Lipopolysaccharide induces aberrant hypermethylation offfic-1 in mouse embryonic fibroblasts lacking p53 gene. (2008)
  • Author(s): Tatemichi M, Hata H. Nakadata T
  • Journal Title: AntiCancer Reseach 28 Pages: 210-8
  • Peer Reviewed
• [Journal Article] Increased risk of gastric cancer in Japanese subjects is associated with microsatellite polymorphisms in the heme oxygenase-1 and the inducible nitric oxide synthase gene promoters. (2008)
  • Author(s): Sawa T, MounawarM, Tatemichi M, et. a
  • Journal Title: Cancer Letter 269 Pages: 78-84
  • Peer Reviewed
• [Journal Article] Different etiological role of Helicobacter pylori (Hp) infection in carcinogenesis between differentiated and undifferentiated gastric cancers (2008)
  • Author(s): Tatemichi M, Sasazuki S, Inoue M, Tsugane S
  • Journal Title: Acta Oncol 47 Pages: 360-5
  • Peer Reviewed
• [Journal Article] Impact of inducible nitric oxide synthase on cancer progression (2008)
  • Author(s): M Tatemichi
  • Journal Title: Eurp. J. Cancer Prev (in press)
  • Peer Reviewed
• [Journal Article] Oxidative and nitrative stress caused by subcutaneous implantation of a foreign body accelerate sarcoma development in Trp53+/- mice (2007)
  • Author(s): Tazawa H, Tatemichi M, Sawa T, Gilibert I, Ma N, Hiraku Y, Donehower LA, Ohgaki H, Kawanishi S, Ohshima H.
  • Journal Title: Carcinogenesis 28 Pages: 191-8
• [Journal Article] Methamphetamine-induced hyperthermia and lethal toxicity : role of the dopamine and serotonin transporters (2007)
  • Author(s): Numachi Y, Ohara A, Yamashita M, Fukushima S, Kobayashi H, Hata H, et.al.
  • Journal Title: Eur J Pharmacol. 573(2-3) Pages: 120-8
• [Journal Article] Methamphetamine-induced locomotor activity and sensitization in dopamine transporter and vesicular monoamine transporter 2 double mutant mice (2007)
  • Author(s): Fukushima S, Shen H, Hata H, et.al.
  • Journal Title: Psychopharmacology (Berl) 193(1) Pages: 55-62
• [Presentation] 炎症によるメチル化と脱メチル化と発がんの関係 (2009)
  • Author(s): 立道昌幸, 畑春実, 中館俊夫
  • Organizer: 日本衛生学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-03-31
• [Presentation] 炎症によるメチル化と脱メチル化と発がん (2009)
  • Author(s): 立道昌幸、畑春実、田澤大、中館俊夫
  • Organizer: 第79回日本衛生学会総会
  • Place of Presentation: 東京
• [Presentation] Frequency Doubling Technology視野計による緑内障検診精度(5年間の追跡調査の結果より) (2008)
  • Author(s): 立道昌幸、中野匡、中館俊夫
  • Organizer: 第81回日本産業衛生学会総会
  • Place of Presentation: 札幌
• [Presentation] 炎症起炎物質(LPS)によるマウスHic1遺伝子CpG islandのmethylationにおけるp53の役割 (2007)
  • Author(s): 立道昌幸、畑春実、田澤大、中館俊夫
  • Organizer: 第77回日本衛生学会総会
  • Place of Presentation: 大阪
• [Presentation] Microchannel array flow analyzeの測定意義 (2007)
  • Author(s): 立道昌幸、久保明、中館俊夫
  • Organizer: 第80回日本産業衛生学会総会
  • Place of Presentation: 大阪