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The development of the 'newly high sensitive biological evaluation method for dental organic materials

Research Project

Project/Area Number 14370627
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 補綴理工系歯学
Research InstitutionTokyo Medical and Dental University

Principal Investigator

HONGO Toshio  Tokyo Medical and Dental Univ., Graduate School, Associate Professor, 大学院・歯学総合研究科, 助教授 (60142444)

Co-Investigator(Kenkyū-buntansha) HIKAGE Sakari  Health Science Univ. of Hokkaido, School of Dentistry, Associate Professor, 歯学部, 助教授 (20134710)
YASUMASU Shigeki  Sophia Univ., Life Science Institute, Associate Professor, 理工学部, 助教授 (00222357)
KITA Kazuo  Chiba Univ., Graduate School of Medicine, Lecturer, 大学院・医学研究院, 講師 (80302545)
HARUMIYA Satoru  Tokyo Medical and Dental Univ., Faculty of Dentistry, Technologist, 歯学部, 技官 (50301792)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2003: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2002: ¥7,700,000 (Direct Cost: ¥7,700,000)
Keywordsbisphenol A / dental resin / human culture cell / transgenic medaka / estrogen responsive element / gene transfer / CYP1A1 gene induction / HPLC / 溶出 / 細胞培養 / メダカ / 変異原性 / 生物学的試験法
Research Abstract

The simply simultaneous method to analyze in the high sensitivity to identify the leached substances from the dental organic materials immersed in saliva and its metabolites was developed using HPLC. It could be clarified the possibility that bisphenol A was immigrated from the polycarbonate orthodontic bracket into the oral cavity and that dibutyl phthalate did also from the temporary filling materials. It became obvious with a child that the daily intake of these substances was the quantity which could not be ignored. The HeLa cell that was introduced genes encoding estrogen responsive element (ERE) and eGFP by retrovirus expression vector, expressed fluorescence when they were stimulated with estradiol-l7β. The lowest concentration of estrogen was 1 ng/mL by which the cells expressed GFP protein 12 hr after the stimulation. RSa-derived cells with up-regulation of human estrogen receptor (hERα) and down-regulation of 78-kDa glucose regulated protein (GRP78) could be established. The … More hERα overproducing cells showed the similar sensitivity to the mutagenic effects of BPA with vector control cells in mutation analysis using ouabain resistance test. However, GRP78-down-regulated cells showed higher sensitivity to BPA mutagenicity than the control cells: the mutagenicity was detected at concentrations over 1 x 10^<-9>〜10^<-8> M in GRP78-down-regulated cells. Thus, GRP78-down-regulated cells may be useful for evaluating mutagenicity of environmental chemicals at very low concentrations. A gene construct Choriogenin L 1.5Kb/GFP to another construct emgb/RFP was linked, injected the double fusion gene construct into 1-or 2-cell-stage embryos, and selected embryos expressing RFP in erythroid cells. When exposed to estradiol-17β, adult fish raised from the embryos showed the liver-specific expression of GFP, suggesting that the 1.5Kb 5'-upstream region promotes estrogen-dependent liver-specific expression of the chg-L gene. This transgenic medaka may be useful as one of test animals for detecting environmental estrogens. BPA alone didn't induce the transcriptional activation of the CYP1A1 gene, but BPA together with 3-methylcholanthrene (MC), superinduced the human CYP1A1 gene. In addition, BPA enhanced the transcriptional activation of the CYP1A1 gene through the AhR/Arnt complex. These results suggested that the superinduction of the human CYP1A1 gene transcription by BPA together with 3-MC is involved in the increasing concentration of intracellular Ca^<2+> to the inhibition of the sarco-endoplasmic reticulum Ca2+-ATPases. From these results, each evaluation developed by this present research can be thought to be the high new sensitive biological evaluation method which can be applied to the basic biological test of the organic material for the dentistry. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] Hikage, S., Saito, T., Takahashi, Y., Kamataki, T., Hongo T.: "Induction of cytochrome P450 1A1 by phthalic esters"Transactions. 16. 295 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Moriya, T., Kita, K., Sugaya, S., Wano, C., Suzuki, N.: "Enhanced expression of the LDH-A gene after gravity-changing stress in human RSa cells"Biol.Sci.Space. 16. 12-17 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wu, Y.P., Kita, K., Suzuki, N.: "Involvement of human heat shock protein 90α in nicotine-induced apoptosis"Int.J.Cancer. 100. 37-42 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arase, Y., Nomura, J., Sugaya, S., Sugita, K., Kita, K., Suzuki, N.: "Effects of 3-D clinostat rotation on gene expression in human fibroblast cells"Cell Biol.Int.. 26. 225-233 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kita, K., Zhai, L., Sugaya, S., Suzuki, N.: "A leukocyte antigen, Leu-13, is involved in induction of resistance of human cells to X-ray cell killing by interferon-α"International Symposium on Biological Effects of Low Dose Radiation. Institute for Environmental Sciences. 129(Abstract). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hikage S, Nakayama K, Saito, T, Takahashi, Y., Kamataki, T., Suzuki, Hongo, T., Sato, A.: "Cytotoxicity of bisphenol A glycidyl dimethacrylate on cytochrome P450 producing cells"J Oral Rehabil. 30. 544-549 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hikage, S, Saito, T, Hongo, T, Tanimura, A, Takahashi, Y, Kamataki, T: "Bispenol A superinduces the human cytochrome P450 1A1 gene transcription through intracellular calcium accumulation"J Dent Res. 82(SI). B-294 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hongo, T., Hikage, S., Harumiya, S., Sato, A.: "Migration of bisphenol A from plastic bracket into human saliva"J Dent Res. 82(SI). B-343 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hasegawa, R., Kita, K., Hasegawa R., et al.: "Induction of apoptosis and ubiquitin hydrolase gene expression by human serumfactors in the early phase of acute myocardial infarction"J Lab.Clin.Med.. 141. 168-178 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahashi, S., Hasegawa, R., KIta, K., et al.: "Increased levels of UV-induced protease activity in human UVAP-1 cells exposed to gravity changing stress : involvement of E-64-sensitive proteases on suppression of UV mutasgenicity"Cell Biol.Int.. 27. 53-60 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kita, K., Sugaya, S., Zhai, L., Wu, YP., et al.: "Involvement of Leu-13 in interferon-induced refractoriness of human RSa cells to X-ray cell killing"Radiat.Res.. 160. 302-308 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chigira, S., Sugita, K., Kita, K., et al.: "Increased expression of the huntington interacting protein-1 gene, in cells from Hutchinson Gilfors syndrome (Progeria) patients and aged donors"J.Gerontology : Biol.Sci.. 58A. 873-878 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zhai, L., Kita, K., Wano, C., Sugaya, S., et al.: "Involvement of molecular chaperone GRP78 in survival and mutability of human cells"Abstract of the 76th Annual Meeting of the Japanese Biochemical Society. 75. 823 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hongo, T., HIkage, S., Sato, A.: "Correlation between cytotoxicity testing and changes in membrane lipid fluidity using dental acrvlic resin monomer"The Journal of the Japanese Society for Dental Materials and Devices. 22. 31-36 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ueno, T., Yasumasu, S., Hayashi S., Iuchi, I.: "Identification of Choriogenin cis-regulatory elements and production of estrogen-inducible liver-specific transgenic Medaka"Mechanism of Development. (In press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hikage, S., Saito, T., Takahashi, Y., Kamataki, T., Hongo, T.: "Induction of cytochrome P450 1A1 by phthalic esters."Transactions. 16. 295 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Moriya, T., Kita, K., Sugaya, S., Wano, C., Suzuki, N.: "Enhanced expression of the LDH-A gene after gravity-changing stress in human RSa cells."Biol.Sci.Space. 16. 12-17 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wu, Y.P., Kita, K., Suzuki, N.: "Involvement of human heat shock protein 90a in nicotine-induced apoptosis."Cell Biol.Int.. 100. 37-42 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arase, Y., Nomura, J., Sugaya, S., Sugita, K., Kita, K., Suzuki, N.: "Effects of 3-D cimostat rotation on gene expression in human fibroblast cells."Cell Biol.Int.. 26. 225-233 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kita, K., Thai, L., Sugaya, S., Suzuki, N.: "A leukocyte antigen, Leu-13, is involved in induction of resistance of human cells to X-ray cell killing by interferon-ct."International Symposium on Biological of Low Dose Radiation, (Institute for Environmental Sciences), Abstract. 129. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hikage, S., Nakayama, K., Saito, T., Takahashi, Y., Kamataki, T., Suzuki, S., Hongo, T., Sato, A.: "Cytotoxicity of bisphenol A glycidyl dimethacrylate on cytochrome P450 producing cells."J Oral Rehabil. 30. 544-549 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hikage, S., Saito, T., Hongo, T., Tanimura, A., Takahashi, Y., Kamataki, T.: "Bisphenol A superinduces the human cytochrome P450 1A1 gene transcription through intracellular calcium accumulation."J Dent Res. 82(SI). B-294 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hongo, T., Hikage, S., Harumiya, S., Sato, A.: "Migration of bisphenol A from plastic bracket into human saliva."J Dental Res. 82(SI). B-343 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hasegawa, R., Kita, K., Hasegawa, R., Fusejinia, K., Fulcuzawa, S., Wano, C., Watanabe, S., Saisho, H., Masuda, Y., Nomura, F., Suzuki N.: "Induction of apoptosis and ubiquitin hydrolase gene expression by human serum factors in the early phase of acute myocardial infarction."J Lab.Chin.Med.. 141. 168-178 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahashi, S., Hasegawa, R., Kita, K., Zhang, H-C., Wano, C., Yamaguchi, Y., Sugaya, S., Nomura, J., Ichinose, M., Suzuki, N.: "Increased levels of UV-induced protease activity in human UVAP-1 cells exposed to gravity-changing stressinvolvement of E-64-sensitive proteases on suppression of UV mutagenicity."Cell Biol.Int.. 27. 53-60 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kita, K., Sugaya, S., Zhai, L., Wu, YP., Wano, C., Chigira, S., Nomura, J., Takahashi, S., Ichinose,.M., Suzuki, N.: "Involvement of Leu-13 in interferon-induced refractoriness of human RSa cells to X-ray cell killing"Radiat.Res.. 160. 302-308 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chigira, S., Sugita, K., Kita, K, Sugaya, S., Arase, Y., Ichinose, M., Shirasawa, H., Suzuki N.: "Increased expression of the huntington interacting protein-I gene, in cells from Hutchinson Gilford syndrome (Progeria) patients and aged donors."J.Gerontology.Biol.Sci.. 58A. 873-878 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zhai, L., Kita, K., Wano, C., Sugaya, S., Aizawa M., Suzuki, N.: "Involvement of molecular chaperone GRP78 in survival and mutability of human cells."Abstract of the 76th Annual Meeting of the Japanese Biochemical Society. 75. 823 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hongo, T., Hikage, S., Sato, A.: "Correlation between cytotoxicity testing and changes in membrane lipid fluidity using dental acrylic resin monomer."The Journal of the Japanese Society for Dental Materials and Devices (in Japanese). 22. 31-36 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ueno, T., Yasumasu, S., Hayashi, S., Iuchi, I.: "Identification of Choriogenin cis-regulatory elements and production of estrogen-inducible, liver-specific transgenic Medaka."Mechanisms of Development. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hongo, T. et al.: "Migration of bisphenol A from plastic bracket into human saliva"J. Dental Res. 82(SI). B-343 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hikage, S., et al.: "Cytotoxicity of bisphenol A glycidyl dimethacrylate on cytochrome P450 producing cells"J Oral Rehabil. 30. 544-549 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takahashi, S. et al.: "Increased levels of UV-induced protease activity in human UVAP-1 cells exposed to gravity-changing stress : involvement of E-64-sensitive proteases on suppression of UV mutagenicity"Cell Biol. Int.. 27. 53-60 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 喜多和子: "ヒト細胞のUV抵抗化における分子シャペロンGRP78の関与"日本放射線影響学会 第46回大会、講演要旨集. 91 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 上野哲郎: "遺伝子導入メダカを用いたコリオジェニン遺伝子の発現調節領域の解析"第74回日本動物学会. (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hikage, S., et al.: "Bisphenol A superinduces the human cytochrome P450 1A1 gene transcription through intracellular calcium accumulation"J. Dental Res. 82(SI). 294 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 本郷敏雄: "ヒト唾液に浸漬したBis-GMA系歯科材料からのビスフェノールA溶出について"歯科材料・器械. 21(SI 40). 122 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hikage, S., et al.: "Induction of Cytochrome P450 lAl by Plithalic Esters"The Forth International Congress on Dental Materials. Transactions.. 16. 295 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 本郷敏雄: "唾液に浸漬した矯正用ポリカーボネート製ブラケットからの溶出物について"第5回日本内分泌撹乱化学物質学会. 380 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 本郷敏雄: "歯科用アクリルレジンモノマーによる細胞毒性試験と膜脂質流動性の変化との相関について"歯科材料・器械. 21・1. 31-36 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hikage, S., et al.: "Cytotoxicity of Bisphenol A glycidyl dimethacrylate on Cytochrome P450 Producing Cells"J Oral Rehabil.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 本郷敏雄: "Bis-GMA系コンポジットレジンからヒト唾液に移行する化学物質について"日本薬学会第123年会講演要旨集. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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