| Direct, Continuous Monitoring of Air Pollution by Transgenic Sensor Mice Responsive to Halogenated and Polycyclic Aromatic Hydrocarbons Ayumi Kasai, Nobuhiko Hiramatsu, Kunihiro Hayakawa, Jian Yao, and Masanori Kitamura Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan Abstract
Background: The aryl hydrocarbon receptor (AhR, also called the dioxin receptor) plays crucial roles in toxicologic responses of animals to environmental pollutants, especially to halogenated and polycyclic aromatic hydrocarbons. To achieve direct, continuous risk assessment of air pollution using biological systems, we generated transgenic sensor mice that produce secreted alkaline phosphatase (SEAP) under the control of AhR. Methods: To characterize responses of the mice to AhR agonists, sensor mice were orally administered 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) , 3-methylcholanthrene (3MC) , benzo[a]pyrene (B[a]P) , or β-naphthoflavone (BNF) , and serum levels of SEAP were evaluated. To monitor air pollution caused by cigarette smoke, we placed the mice each day in an experimental smoking room, and evaluated activity of serum SEAP for up to 4 days. Activation of AhRin individual organs was also examined by reverse transcription–polymerase chain reaction (RT-PCR) analysis of SEAP. Results: In response to oral exposure to TCDD, sensor mice exhibited dramatic and sustained activation of AhR. The mice also responded sensitively to 3MC, B[a]P, and BNF. Activation of AhR was dose dependent, and the liver was identified as the main responding organ. After exposure to the smoking environment, sensor mice consistently exhibited transient, reversible activation of AhR. RT-PCR analysis of SEAP revealed that activation of AhR occurred predominantly in the lung. Conclusion: We are the first laboratory to demonstrate successfully direct, comprehensive monitoring of air pollution using genetically engineered mammals. The established system would be useful for real risk assessment of halogenated and polycyclic aromatic hydrocarbons in the air, especially in smoking environments. Key words: aromatic hydrocarbon, aryl hydrocarbon receptor (AhR) , cigarette smoke, dioxin-responsive element (DRE) , secreted alkaline phosphatase (SEAP) , transgenic mouse. Environ Health Perspect 116:349–354 (2008) . doi:10.1289/ehp.10722 available via http://dx.doi.org/ [Online 20 December 2007]
Address correspondence to M. Kitamura, Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi 409-3898, Japan. Telephone: 81-55-273-8054. Fax: 81-55-273-8054. E-mail: masanori@yamanashi.ac.jp Supplemental Material is available online at http://www.ehponline.org/members/2007/10722/suppl.pdf We thank M. Denison (University of California) for providing plasmids. This work was supported by a grant from The Smoking Research Foundation to M.K. A.K. and K.H. are Research Fellows of the Japan Society of the Promotion Science. The authors declare they have no competing financial interests. Received 31 July 2007 ; accepted 19 December 2007.
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