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Development of risk assessment system for human by environmental disruptants using nuclear hormone receptor

Research Project

Project/Area Number 11839021
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research InstitutionYokohama City University

Principal Investigator

DOI Rikuo  Yokohama City University, School of Medicine, Professor, 医学部, 教授 (70091585)

Co-Investigator(Kenkyū-buntansha) MATSUI Mitsuaki  Yokohama City University, School of Medicine, Research Associate, 医学部, 助手 (00285115)
KASHIMA Yuji  Yokohama City University, School of Medicine, Research Associate, 医学部, 助手 (50233705)
OKABE Toshiko  Yokohama City University, School of Medicine, Associate Professor, 医学部, 助教授 (20152564)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordsendocrine disruptants / thyroid hormone receptor / thyroid hormone response element / T_3 / reporter assay / luciferase / hydroxylated PCB / dioxin / 甲状腺ホルモンレセプター / リポーターアッセイ / ホルモンレスポンスエレメント / direct repeat(DR)4 / DRO / レチノイン酸Xレセプター / テトラサイクリン
Research Abstract

Endocrine disruptants are thought to have various effects on various organs. Estrogenic responses by endocrine disruptants were analyzed using eukaryotic cells and yeast, which are overexpressing human estrogen receptors. In wildlife, some species such as seagulls contaminated with large amount of environmental pollutants showed thyroid hyperplasia and thyroid tumors. To address the effects on thyroid hormone system by endocrine disruptants, the HeLaTR cells that constitutively overexpressed thyroid hormone receptor were constructed and analyzed. Luciferase activity was induced by the addition of T3 in HeLaTR cells transfected with the plasmid containing thyroid hormone response element as an enhancer. Bisphenol A and 2-diethylhexyl phtalate, both could bind to estrogen receptor, had no effect on the luciferase activity, but hydroxylated PCB repressed the luciferase activity caused by the addition of T3. In contrast, dioxin enhanced the luciferase activity, however dioxin alone caused no effect on the activity. These results suggested that HeLaTR cells could be used as the tool for thyroid hormone action by endocrine disruptants.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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