A century ago, coal miners relied on canaries as sentinels, using them as an early warning signal for toxic gases like methane and carbon monoxide.  Now, researchers in Japan have engineered transgenic mice to serve as in vivo biosensors for the detection of environmental pollutants. 

Two of the most common air pollutants are halogenated and polycyclic aromatic hydrocarbons.  Overexposure to these contaminants can lead to a spectrum of deleterious effects in humans and other mammals, including cancer, birth defects, and immunological disorders.  The primary mechanism of action for this toxicity involves the activation of the aryl hydrocarbon receptor (AhR, also called the dioxin receptor) in tissues exposed to these compounds.

It is currently standard practice to monitor the presence of aromatic hydrocarbons in food and environmental samples through the use of physicochemical methods such as gas chromatography-mass spectrometry (GC-MS).  While effective at this task, these methods are nevertheless not suitable for determining the actual risk of such pollutants in humans – by taking into account their relative bioavailability and metabolism, for example.  Furthermore, current methods cannot estimate the potential effects of synergism and antagonism among the large number of toxic and nontoxic compounds present in environmental samples.

As humans are exposed to a plethora of xenobiotics through a number of routes – respiratory, transdermal, ingestive – it is clear that current monitoring approaches are unable to accurately measure the combinatorial and/or long-term effects of these chemicals on our health.  To address this challenge, a team around Masanori Kitamura – of the University of Yamanashi in Japan – has developed transgenic mice that release secreted alkaline phosphase (SEAP, an easily-detected biomarker) into their circulation in response to activation of AhR.  By simply sampling the blood of these animals for measurement of SEAP levels, it therefore becomes possible to carry out direct, comprehensive and real-time monitoring of dioxin-like substances, including those present in air.

More recently, in the March 2008 issue of Environmental Health Perspectives, Kitamura and colleagues describe the use of these transgenic mice to carry out the direct, comprehensive monitoring of air pollution.  In preliminary experiments, the AhR:SEAP mice were to found to respond – clearly, and in a dose-dependent fashion – with raised SEAP levels to oral administration of AhR agonists such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene (3MC), benzo[a]pyrene (B[a]P), and β-naphthoflavone (BNF).  Reverse transcription-polymerase chain reaction (RT-PCR) analysis of these treated mice revealed the primary responding organ to be the liver.

In a next set of experiments, the transgenic mice were exposed for several days to the air of an experimental smoking room.  Here, the SEAP levels of exposed mice were increased in a transient, reversible manner, and RT-PCR analysis indicated that this activation occurred primarily in the lung.

It appears, therefore, that genetic engineering has successfully created a 21st-century equivalent of a canary in a coal mine.  Rather than simply offering a binary assessment of environmental contamination – i.e., by living or dying – this elegant biosensor system promises to complement existing monitoring platforms by enabling the assessment of real risk to human health by airborne aromatic hydrocarbons.

Article by Kasai et al. on pollution-monitoring biosensor mice, Environmental Health Perspectives, March 2008