Formation of Hydroxylated Metabolites Responsible for the Toxicity of Brominated Flame Retardants and Thyroid Hormone Disrupting Action
| Project/Area Number |
18590118
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental pharmacy
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| Research Institution | Nihon Pharmaceutical University |
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Principal Investigator |
KITAMURA Shigeyuki Nihon Pharmaceutical University, School of Pharmacy, Professor (40136057)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIMOTO Nariaki Hiroshima University, Reseanch Institute for Radiation Biology and Medicine, Associate Professor (40243612)
KASHIWAGI Akihiko Hiroshima University, Graduate School of Sciences, Professor (50106796)
OHTA Shigeru Hiroshima University, Graduate Shool of Biomedical Scienoes, Professor (60160503)
SUGIHARA Kazumi Hiroshima University, Graduate Shool of Biomedical Sciences, Research Associate (20271067)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,680,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥180,000)
Fiscal Year 2007: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2006: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | Endocrine disruptor / Brominated flame retardant / Tetrabromobisphenol A / Polybromodiphenyl ether / Thyroid hormonal activity / Estrogenic activity / Metabolic activation / Amphibian metamorphosis / ブロム化難燃剤 / ポリブロモジフェニールエーテル / 甲状腺ホルモン / 内分泌撹乱作用 |
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| Research Abstract |
Endocrine-disrupting activity of some brominated flame retardants was examined. 1) The thyroid hormone-disrupting activity of tetrabromobisphenol A, tetrachlorobisphenol A, some 4-hydroxylated polybromodiphenyl ethers was observed in the assay of binding to thyroid hormone receptor. These chemicals also showed thyroid hormonal effect on GH3 cell. However, polybrominated diphenyl ethers and bisphenol A did not exhibit the activity. Especially, tetrabromobisphenol A exhibited the highest thyroid hormonal activity. 3, 5-Substituted bromide is an essential factor for the thyroid hormonal activity. 2) 4-Hydroxy-2, 2', 4-tribromodiphenyl ether exhibited estrogenic activity in the reporter assay using human breast cancer cell line MCF-7. In this case, 3, 5-dibromo substitution decreased the estrogenic activity. 3) The action of these chemicals was also estimated by amphibian metamorphosis using tadpole. The tail of tadopole was shortened by the addition of triiodothyronine (T3). These chemicals showed antagonistic effect against the T3-induced tadpole tail regression. These facts suggest that hydroxylated brominated flame retardants exhibited endocrine-disrupting effect in the worldwide life.
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Report
(3 results)
Research Products
(28 results)
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[Journal Article] In vivo function of the 5'fianking region of mouse estrogen receptor beta gene. Yoshito Tezuka, Kyoko Takahashi, Tomoharu Suzuki, Shigeyuki Kitamura2007
Author(s)
N., Fujimoto, O., Nakajima, S., Kitamura, S., Ohta
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Journal Title
J Steroid Biochem Mol Biol 105
Pages: 57-62
Description
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[Journal Article] The in vitro metabolism of a pyrethroid insecticide, permethrin, and its hydrolyzed oroducts in rats2007
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Y., Nakamura, K., Sugihara, T., Sone, M., Isobe, S., Ohta, S., Kitamura
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Journal Title
Toxicology 235
Pages: 176-184
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[Journal Article] Comparative study of aryl hydrocarbon receptor ligand activities of six chemicals in vitro and in vivo2007
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K., Sugihara, T., Okayama, S., Kitamura, K., Yamashita, M., Yasuda, S., Miyairi, Y., Minobe, S., Ohta
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Journal Title
Archives of Toxicology 82
Pages: 5-11
Description
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[Journal Article] Suppression of amphibian metamorphosis by bisphenol A and related chemical substances2006
Author(s)
Y., Goto, S., Kitamura, K., Kashiwagi, K., Oofusa, O., Tooi, K., Yoshizato, J., Sato, S., Ohta, A., Kashiwagi
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Journal Title
Journal of Health Sciences 52(2)
Pages: 160-168
NAID
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[Journal Article] Effects of stilbene and related compounds on reproductive organs in B6C3F1/Crj mouse H. Fujita, Y. Okimura, T. Utsumi, S. Kitamura, H. Kuroki, T. Otsuki, J. Sasaki, A. Kashiwag2006
Author(s)
S., Sanoh, S., Kitamura, R., Kohta, K., Sugihara, S., Ohta, H., Watanabe
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Journal Title
Journal of Health Sciences 52(5)
Pages: 613-622
Description
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[Presentation] Thyroid hormonal and estrogenic activity of OH-PCB and OH-PBDE in cell culture2007
Author(s)
S., Kitamura, T., Suzuki, K., Sugihara, N., Uramaru, H., Kuroki, N., Fujimoto, S., Ohta
Organizer
DIOXIN 2007
Place of Presentation
Tokyo Japan
Description
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[Presentation] The S-oxidation of PCB methyl ulfoxise to PCB methyl sulfone with animal liver microsomes and human cytochrome P4502007
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H., Kuroki, H., Nakai, A., Toda, M., Mitsutake, R., Eyanagi, S., Kitamura
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DIOXIN 2007
Place of Presentation
Tokyo Japan
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[Presentation] Screening of AhR-binding, estrogenic and antiandrogenic activities of benzophenone derivatives used as UV stabilizers and sunscreens2007
Author(s)
K., sugihara, S., Shinohara, T., Suzuki, N., Fujimoto, S., Kitamura, S., Ohta
Organizer
DIOXIN 2007
Place of Presentation
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[Presentation] Parabens and phthalates : Their metabolism, AhR ligand activity, estrogenic Activity, and P450-inhibitory activity2007
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H., Oz-aki, S., Shinohara, S., Tange, K., Sugihara, S., Kitamura, S., Ohta
Organizer
DIOXIN 2007
Place of Presentation
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[Presentation] In vivo and in vitro metabolism of zaleplon in chimeric mice with humanized liver2007
Author(s)
C., Tanoue, K., Sugihara, S., Kitamura, T., Inoue, T., Horie, S., Ohta
Organizer
8th, International ISSX Meeting
Place of Presentation
Sendai Japan
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[Presentation] Chimeric mice with humanized liver as a model to predict diazepam metabolism in humans.2007
Author(s)
T., Inoue, K., Sugihara, S., Kitamura, H., Ohshita, T., Horie, S., Ohta
Organizer
8th International ISSX Meeting
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