Direct, continuous monitoring of air pollution by transgenic sensor mice responsive to halogenated and polycyclic aromatic hydrocarbons.
Direct, continuous monitoring of air pollution by transgenic sensor mice responsive to halogenated and polycyclic aromatic hydrocarbons.
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DOI：
10.1289/ehp.10722
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发表时间：
2008-03
影响因子：
10.4
通讯作者：
Kitamura M
中科院分区：
文献类型：
--
作者：
Kasai A;Hiramatsu N;Hayakawa K;Yao J;Kitamura M
芳烃受体（AhR，也称二恶英受体）在动物对环境污染物，特别是卤代芳烃和多环芳烃的毒理反应中起着重要作用。为了实现直接的，连续的空气污染的风险评估，使用生物系统，我们产生了转基因传感器小鼠分泌碱性磷酸酶（SEAP）的AhR的控制下。为了表征小鼠对AhR激动剂的反应，传感器小鼠经口给予2，3，7，8-四氯二苯并-p-二恶英（TCDD）、3-甲基胆蒽（3 MC）、苯并[a]芘（B[a]P）或β-萘酮（BNF），并评价血清SEAP水平。为了监测由香烟烟雾引起的空气污染，我们每天将小鼠置于实验吸烟室中，并评估血清SEAP的活性长达4天。还通过SEAP的逆转录-聚合酶链反应（RT-PCR）分析检查了单个器官中AhR的激活。在响应口服暴露于TCDD，传感器小鼠表现出显着和持续激活的AhR。小鼠对3 MC、B[a]P和BNF也有敏感反应。AhR的激活是剂量依赖性的，并且肝脏被确定为主要的响应器官。暴露于吸烟环境后，传感器小鼠始终表现出短暂的，可逆的激活AhR。SEAP的RT-PCR分析显示AhR的激活主要发生在肺中。我们是第一个成功展示使用基因工程哺乳动物直接、全面监测空气污染的实验室。建立的系统将是有用的真实的风险评估的卤代和多环芳烃在空气中，特别是在吸烟环境。
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. 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 AhR in individual organs was also examined by reverse transcription–polymerase chain reaction (RT-PCR) analysis of SEAP. 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. 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.
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影响因子：
4.4
作者：
Nohara, K;Pan, XQ;Tohyama, C
通讯作者：
Tohyama, C
影响因子：
3.8
作者：
DILIBERTO, JJ;AKUBUE, PI;BIRNBAUM, LS
通讯作者：
BIRNBAUM, LS
影响因子：
5.8
作者：
Nebert, DW;Roe, AL;Dalton, TP
通讯作者：
Dalton, TP
影响因子：
3.8
作者：
Operana, Theresa N.;Nguyen, Nghia;Tukey, Robert H.
通讯作者：
Tukey, Robert H.
影响因子：
2.9
作者：
Kasai, A;Hiramatsu, N;Kitamura, M
通讯作者：
Kitamura, M