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Development of bioassay system for evaluating the (anti-) thyroid hormone-like activity by various environmental contaminants

Research Project

Project/Area Number 14570303
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionYokohama City University

Principal Investigator

OKABE Toshiko  Yokohama City University, School of Medicine, Associate Professor, 医学部, 助教授 (20152564)

Co-Investigator(Kenkyū-buntansha) KASHIMA Yuji  Yokohama City University, School of Medicine, Assistant Professor, 医学部, 助手 (50233705)
SAKAI Haruya  Yokohama City University, School of Medicine, Assistant Professor, 医学部, 助手 (20303555)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2004: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsthyroid hormone / thyroid hormone receptor / organohalogen compounds / endocrine disrupters / reporter assay / estrogen receptor / thyroid hormone response element / 有機ハロゲン態ハロゲン化合物 / 環境汚染物質 / DNAマイクロアレー / 農薬 / 臭素化難燃剤 / 4-1BB / 内分泌攪乱物質 / 難燃剤
Research Abstract

It had been reported that reproductive and immune systems were affected in wildlife containing high concentrations of dioxins and/or polychlorinated biphenyls (PCBs). Recently the organohalogen compounds which have structural similarities with thyroid hormone have been used widely as flame retardants and some of them are detected in environmental samples. From these facts, it has been suspected that these organohalogen compounds may affect on wildlife as well as human beings as environmental contaminants. In this work, we constructed the bioassay system using transcriptional activation by thyroid hormone receptor as biomarkers. First, we established human cell line in which thyroid hormone receptor α gene was stable transfected and designated HeLaTR cells. Then DR4-SV-Luc plasmid in which thyroid hormone response element (DR4) was inserted upstream of luciferase gene was transfected into HeLaTR cells transiently in the presence or absence of T3. Luciferase activities were determined us … More ing cell lysate and it was found that T3 increased luciferase activity four to five fold. After addition of various organohalogen compounds such as environmental contaminants to this bioassay system, luciferase activities in each cell lysates were determined to evaluate the effects on thyroid hormone system by organohalogen compounds. One hydroxylated PCB, which was the metabolite of PCB turned to reduce the luciferase activity which was induced by T3 in HeLaTR cells. In contrast, dioxin, hexacyclododecane which is used for flame retardant, and nitrofen which had been used for pesticide augmented the luciferase activities induced by T3. Diiodobiphenyl (DIB) which is used for photoconductor of cellular phone could induce luciferase activity and augment the T3 action. Furthermore, DIB could augment the transcriptional activation by estrogen receptor through estrogen response element. We also determined the gene expression profile after addition of T3 into HeLaTR cells by DNA microarray, and showed that apoptosis signal through 4-1BB was activated after addition of T3. Less

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (8 results)

All 2005 2004 2003 Other

All Journal Article (6 results) Publications (2 results)

  • [Journal Article] Modulation at a cellular level of the thyroid hormone receptor-mediated gene expression by 1,2,5,6,9,10-hexabromocyclododecane (HBCD), 4,4'-diiodobiphenyl (DIB), and nitrofen (NIP).2005

    • Author(s)
      Yamada-Okabe, T et al.
    • Journal Title

      Toxicology Letters 155

      Pages: 127-133

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Modulation at a cellular level of the thyroid hormone receptor-mediated gene expression by 1,2,5,6,9,10-hexabromocyclododecane (HBCD), 4,4' -diiodobiphenyl (DIB), and nitrofen (NIP)2005

    • Author(s)
      Yamada-Okabe, T et al.
    • Journal Title

      Toxicology Letters 155

      Pages: 127-133

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 2,3,7,8-tetrachlorodibenzo-p-dioxin augments the modulation of gene expression mediated by the thyroid hormone receptor.2004

    • Author(s)
      Yamada-Okabe, T et al.
    • Journal Title

      Toxicology and Applied Pharmacology 194

      Pages: 201-210

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] 2,3,7,8-tetrachlorodibenzo-p-dioxin augments the modulation of gene expression mediated by the thyroid hormone receptor2004

    • Author(s)
      Yamada-Okabe, T et al.
    • Journal Title

      Toxicology and Applied Pharmacology 194

      Pages: 201-210

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Thyroid hormone induces the expression of 4-1BB and activation of caspases in a thyroid hormone receptor dependent manner.2003

    • Author(s)
      Yamada-Okabe, T et al.
    • Journal Title

      European journal of Biochemistry 270

      Pages: 3064-3073

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Thyroid hormone induces the expression of 4-1BB and activation of caspases in a thyroid hormone receptor dependent manner2003

    • Author(s)
      Yamada-Okabe, T et al.
    • Journal Title

      European Journal of Biochemistry 270

      Pages: 3064-3073

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Yamada-Okabe T, et al.: "Thyroid hormone induces the expression of 4-1BB and activation of caspases in a thyroid hormone receptor dependent manner"European Journal of Biochemistry. 270. 3064-3073 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamada-Okabe T, et al.: "2,3,7,8-tetrachlorodibenzo-p-dioxin augments the modulation of gene expression mediated by the thyroid hormone receptor"Toxicology and Applied Pharmacology. 194. 201-210 (2004)

    • Related Report
      2003 Annual Research Report

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

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