title: Direct, continuous monitoring of air pollution by transgenic sensor mice responsive to halogenated and polycyclic aromatic hydrocarbons.
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 beta-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 AhR in 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kasai
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hiramatsu
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Jian
authors.initials: J
authors.lastname: Yao
authors.forename: Masanori
authors.initials: M
authors.lastname: Kitamura
mesh_terms: D000469:Alkaline Phosphatase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004784:Environmental Monitoring / Q000379:methods*; D005240:Feasibility Studies; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000032:analysis*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis*; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014028:Tobacco Smoke Pollution / Q000032:analysis*
chemical_list: D006846:Hydrocarbons, Halogenated; D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon; D014028:Tobacco Smoke Pollution; D019363:Cytochrome P-450 CYP1A1; D000469:Alkaline Phosphatase