Evaluation of toxic activities of polycyclic aromatic hydrocarbon derivatives using in vitrobioassays
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概要
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Several polycyclic aromatic hydrocarbons and nitrated polycyclic aromatic hydrocarbons (PAHs/NPAHs) such as benzo[a]pyrene and 1-nitropyrene are mutagens and/or carcinogens. These compounds secondarily generate PAH hydroxides, ketones, and quinones through atmospheric and metabolic reactions. The health effects of these compounds is now an important social concern. For example, lung cancer, bronchitis, whistling and so on. In this work, we evaluated toxicities of 25 PAH derivatives (hydroxides, ketones and quinones) in terms of aryl hydrocarbon receptor (AhR) binding and thyroid hormone-related endpoints using three in vitro bioassays: dioxinresponsive chemical-activated luciferase gene expression (DR-CALUX), thyroid receptor β chemical-activated luciferase gene expression (TRβ-CALUX), and competitive human transthyretin-binding (TTR-binding) assays. Eleven of the 25 PAH derivatives had AhR agonist activity, six had AhR antagonist activity and seven had TRpotentiation activity in the TR-CALUX. Furthermore, PAH quinones and hydroxides had strong TTR-binding activity. 3,4-Dihydrobenz[a]anthracen-1(2 H)-one had the strongest agonist activity (EC20: 0.4μM) as determined by DR-CALUX. PAH ketones showed stronger activity than the control and significant difference by statistical analysis. Benzo[c]phenanthrene-[1,4]-quinone was the most TTR-active compound (IC50: 2.5μM). Both PAH ketones and quinones, which have functional groups with low polarity, had significant activities in all tested assays. These in vitro results suggest that PAH derivatives might have various toxic activities in animals. For estimating the health effects and accessing the environmental risks of PAHs, further studies on the toxicity mechanisms are necessary. ©2009 The Pharmaceutical Society of Japan.
著者
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Bekki Kanae
Graduate School of Natural Science and Technology, Kanazawa University
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Takigami Hidetaka
Research Center for Material Cycles and Waste Management, National Institute for Environmental Studi
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Suzuki Go
Research Center for Material Cycles and Waste Management, National Institute for Environmental Studi
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Tang Ning
Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University
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Hayakawa Kazuichi
Graduate School of Natural Science and Technology, Kanazawa University
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Hayakawa Kazuichi
Graduate School Of Natural Science And Technology Faculty Of Pharmaceutical Sciences Kanazawa Univer
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Takigami Hidetaka
Research Center For Material Cycles And Waste Management National Institute For Environmental Studie
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Tang Ning
Institute Of Medical Pharmaceutical And Health Sciences Kanazawa University
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Suzuki Go
Research Center for Material Cycles and Waste Management, National Institute for Environmental Studies
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Hayakawa Kazuichi
Graduate School of Medical Sciences, Division of Pharmaceutical Sciences, Kanazawa University
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