Activation of the Human Ah Receptor by Aza-Polycyclic Aromatic Hydrocarbons and Their Halogenated Derivatives.
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- Saeki Ken-ichi
- Faculty of Graduate School of Pharmaceutical Sciences, Nagoya City University
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- Matsuda Tomonari
- Department of Environmental Engineering, Kyoto University
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- Kato Taka-aki
- Faculty of Graduate School of Pharmaceutical Sciences, Nagoya City University
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- Yamada Katsuya
- Faculty of Graduate School of Pharmaceutical Sciences, Nagoya City University
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- Mizutani Takaharu
- Faculty of Graduate School of Pharmaceutical Sciences, Nagoya City University
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- Matsui Saburo
- Department of Environmental Engineering, Kyoto University
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- Fukuhara Kiyoshi
- Division of Organic Chemistry, National Institute of Health Sciences, Japan
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- Miyata Naoki
- Faculty of Graduate School of Pharmaceutical Sciences, Nagoya City University Division of Organic Chemistry, National Institute of Health Sciences, Japan
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抄録
Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor through which dioxins and carcinogenic polycyclic aromatic hydrocarbons cause altered gene expression and toxicity. Ten aza-polycyclic aromatic hydrocarbons (aza-PAHs), consisting of nitrogen substituted naphthalenes, phenanthrenes, chrysenes, and benzo[a]pyrenes (BaPs), were subjected to analysis of their structure-activity relationships as an AhR ligand by using a yeast AhR signaling assay, in which AhR ligand activity was evaluated as lacZ units. Most of the aza-PAHs showed similar or more potent AhR ligand activities than the corresponding parent PAHs. About a 100-fold increased in ligand activity was observed in 10-azaBaP compared with BaP. Halogen-substitution effects on AhR ligand activity in aza-polycyclic aromatics were also investigated with quinoline, benzo[f]quinoline (BfQ), benzo[h]quinoline (BhQ) and 1,7-phenanthroline (1,7-Phe). Position-specific induction of AhR ligand activity was observed in aza-tricyclic aromatic compounds, BfQ, BhQ, and 1,7-Phe, and the ratio of the ligand activities (lacZ units/μM) of monochlorinated and monobrominated aza-tricyclic aromatic compounds to those of the corresponding parent non-halogenated compounds ranged from 2.2- to 254-fold. Greatest enhancement of ligand activity was observed in 2-brominated BfQ (2-Br-BfQ), and its ligand activity was higher than that of BaP. These results suggest that even monohalogenation markedly enhances AhR ligand activity in aza-PAHs.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 26 (4), 448-452, 2003
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204626490880
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- NII論文ID
- 110003608452
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- NII書誌ID
- AA10885497
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- COI
- 1:CAS:528:DC%2BD3sXltVaqur0%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 6492161
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- PubMed
- 12673023
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可