Sammendrag
In the Adverse Outcome Pathway (AOP) concept, the molecular initiating event (MIE) represents the binding of the toxicant to its target, often a receptor inside a cell or on the cellular surface. MIEs lead to a cascade of downstream key events (KE), which can result in an adverse outcome, i.e. toxicity. The aryl hydrocarbon receptor (Ahr) and the nuclear receptors (NRs) comprise important MIE targets for environmental pollutants. These receptors are able to bind and be activated by a wide range of xenobiotic chemical compounds, acting as xenosensors, and as transcription factors their modulation may lead to physiological perturbation representing endocrine and metabolic disruption.
Knowledge about the specificity and sensitivity of xenosensors in wildlife in general, and in key indicator species in particular, is an important aspect of ecotoxicological research. This knowledge is also the basis for developing receptor-based bioassays for use in environmental monitoring and toxicity testing. The Atlantic cod (Gadus morhua) is a fish species of high importance in pelagic and coastal ecosystems of the North Atlantic, as well as in Norwegian fisheries. It is also a widely used indicator species in environmental monitoring programs in Europe.
In the dCod 1.0 project (NFR 2016-2021) we have cloned and characterized the two cod Ahrs as well as a number of cod NRs. For each receptor, we have established a luciferase gene reporter assay (LRA), where single compounds, mixtures, and environmental extracts have been tested. Using this battery of LRAs, we have shown how 11 different bisphenol A (BPA) analogs present similar, and sometimes stronger, endocrine disrupting properties, by activation of the cod Er. Using extracts from sediments representing a gradient of pollution from the inner parts of Byfjorden in Bergen to relatively pristine reference sites, we observe strong receptor activation at the more polluted sites. In the PW-exposed project, we are characterizing the toxicity of produced water from petroleum production using fractionated extracts, pinpointing specific fractions with the highest Ahr activating potency.
Together, our results demonstrate that a battery of receptor-based bioassays are useful in environmental monitoring and toxicity testing, at the same time advancing our knowledge of environmental risk from various complex pollution sources.
The studies were funded by the Norwegian Research Council through the projects dCod 1.0 (248840), iCod 2.0 (244564), and PW-exposed (280511).
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