Studies on the effects of dioxin on bone mineralization, vitamin D metabolism and calcium(Ca)homeostasis in the growing mouse

2008 Fiscal Year Final Research Report

• Project/Area Number: 19510075
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: National Institute for Environmental Studies
• Principal Investigator: NISHIMURA Noriko National Institute for Environmental Studies, 環境リスク研究センター, 主任研究員 (10097800)
• Project Period (FY): 2007 – 2008
• Keywords: ダイオキシン / 腎臓 / Ca吸収 / ビタミンD代謝 / 骨形成

Research Abstract

内分泌撹乱物質のダイオキシン(2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD)によるビタミンD、骨Ca代謝および骨形成に及ぼす影響とその毒性発現メカニズムを解明するために研究をおこなった。出産1日目に体重kg当たり15μgのTCDDを経口的に投与した母マウスの母乳を介して仔マウスにTCDDを曝露し、検体を採取して骨代謝関連因子を組織学的、生化学的、分子生物学的に分析しその発現機構を総合的に解析した。本研究は、TCDDが活性型ビタミンD合成を促進させる結果、血中のビタミンDの恒常的な高濃度をもたらし、この高ビタミンD血症が骨芽細胞の活性抑制と骨の石灰化を阻害するというダイオキシンの骨毒性発現の本態を明らかにした。

Research Products

• [Journal Article] Dioxin-induced up-regulation of the active form of vitamin D is the maincause for its inhibitory action onosteoblast activities leading to developmental bone toxicity (2009)
  • Author(s): Nishimura N, Nishimura H, Ito T, Miyata C, Izumi K, Fujimaki H, Matsumura F
  • Journal Title: Toxicology and Applied Pharmacology 236 Pages: 301-309
  • Peer Reviewed
• [Journal Article] Critical role of cyclooxygenase-2 activation in pathogenesis of hydronephrosis causedby lactational exposure of mice to dioxin (2008)
  • Author(s): Nishimura N, Matsumura F, Vogel FA, Nishimura H, Yonemoto J, Yoshioka W, Tohyama
  • Journal Title: Toxicology and Applied Pharmacology 231 Pages: 374-383
  • Peer Reviewed
• [Journal Article] Role of metallothionein as a protective factor against radiation carcinogenesis (2008)
  • Author(s): Shibuya K, Nishimura N, Suzuki J, Tohyama C, Naganuma A, Satoh M
  • Journal Title: The Journal of Toxicological Sciences 33(5) Pages: 651-655
  • Peer Reviewed
• [Journal Article] Defect of mineralization as a possible cause of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced bone toxicity in early postnatal development in mice (2008)
  • Author(s): Nishimura N, Ito T, Fujimaki H, Nishimura H
  • Journal Title: 28th International Symposium on Halogenated Persistent Organic Pollutants(POPs) 70 Pages: 1924-1927
• [Journal Article] Modulation of the chemokines KC and MCP-1 by 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Mice (2007)
  • Author(s): Vogel C, Nishimura N, Sciullo E, Wong P, Li W, Matsumura F.
  • Journal Title: Arch. Biochem Biophys. 461 Pages: 169-175
  • Peer Reviewed
• [Journal Article] Up-regulation of 25-hydroxyvitamin D3 1-hydroxylase and disruption of calcium metabolism by 2,3,7,8-tetrachlorodibenzo-p-dioxin in developing mouse kidney (2007)
  • Author(s): Noriko N, Miyata C, Ito T, Izumi K, Fujimaki H, Nishimura H
  • Journal Title: Organohalogen Compounds 69 Pages: 1079-1082
• [Presentation] マウス腎におけるダイオシシンによるビタミンD代謝撹乱と骨形成への影響 (2008)
  • Author(s): 西村典子、伊藤智彦、泉恵子、藤巻秀和、西村久雄
  • Organizer: 第78回日本衛生学会総会
  • Place of Presentation: 熊本
  • Year and Date: 20080300
• [Presentation] Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on bone mineralization in the growingmouse. (2008)
  • Author(s): Nishimura N, Ito T, Izumi K, FujimakiH, Nishhimura H
  • Organizer: SOT Annual meeting
  • Place of Presentation: Seattle, USA
  • Year and Date: 20080000
• [Presentation] Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on born development in mouse pups (2008)
  • Author(s): Nishimura N
  • Organizer: Eurotox 2008
  • Place of Presentation: Rhodes
  • Year and Date: 2008-10-06
• [Presentation] Defect of mineralization as a possible cause of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced bone toxicity in early postnatal development in mice (2008)
  • Author(s): Nishimura N
  • Organizer: 28th International Symposium on Halogenated Persistent Organic Pollutants(POPs)
  • Place of Presentation: Birmingham
  • Year and Date: 2008-08-19
• [Presentation] Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on bone mineralization, vitamin D metabolism and calcium(Ca)homeostasis in the growing mouse (2008)
  • Author(s): Nishimura N
  • Organizer: 5th SETAC World Congress
  • Place of Presentation: Sydney
  • Year and Date: 2008-08-05
• [Presentation] Bone toxicity through dioxin-mediated disorders of vitamin D metabolism and Ca reabsorption in mouse kidney (2008)
  • Author(s): Nishimura N
  • Organizer: Gordon Research Conferences Environmental Endocrine Disruptors
  • Place of Presentation: Boston
  • Year and Date: 2008-06-11
• [Presentation] マウス腎臓のビタミンD代謝およびカルシウム輸送に及ぼす2,3,7,8-tetrachlorodibenzo-p-dioxinの撹乱作用 (2007)
  • Author(s): 西村典子、宮田千恵、伊藤智彦、泉恵子、藤巻秀和、西村久雄
  • Organizer: 第34回日本トキシコロジー学会, Vol.32, P.S98
  • Place of Presentation: 東京
  • Year and Date: 20070300
• [Presentation] Changes of gene expression involved in vitaminm D etabolism and transcellular Ca2+transport by 2,3,7,8-tetrachlorodibenzo-p-dioxin developing mouse kidney (2007)
  • Author(s): Nishimura N, Miyata C, Ito T, Izumi K,Fujimaki H, Nishimura H
  • Organizer: International Congress of Toxicology
  • Place of Presentation: Montreal, Canada
  • Year and Date: 20070000
• [Presentation] 発育期マウスにおけるダイオキシンのビタミンD代謝撹乱と骨毒性 (2007)
  • Author(s): 西村典子、伊藤智彦、宮田千恵、泉恵子、藤巻秀和、西村久雄
  • Organizer: 日本内分泌撹乱化学物質、第10回研究発表会 p.179
  • Place of Presentation: さいたま市
  • Year and Date: 20070000
• [Book] ダイオキシンの生殖発生影響とその病態発症のメカニズム, 細胞工学 Vol.26、No. 12 (2008)
  • Author(s): 遠山千春、大迫誠一郎、石村隆太、西村典子、吉岡亘
  • Total Pages: 1380-1385
• [Book] 周産期ダイオキシン曝露がもたらす甲状腺毒性発現メカニズム, Biophilia Vil.4 No. 1 (2008)
  • Author(s): 西村典子
  • Total Pages: 30-34