Integrated OMICS and imaging for a better understanding of ecotoxicological mechanisms

Main funder

Funder's project number: 294066

Funds granted by main funder (€)

Funding program

Project timetable

Project start date: 01/09/2015

Project end date: 31/08/2018

Summary

Polynuclear aromatic hydrocarbons (PAHs) are ubiquitous contaminants in the environment. Many of them cause developmental defects in vertebrates, embryonic fish being the most sensitive. The mechanisms of toxicity are still largely unresolved. The developmental toxicity of some PAHs depends on the aryl hydrocarbon receptor (AhR), but the events between AhR activation and developmental defects are still not clear. The molecular mechanisms involved in the cardiovascular toxicity of PAHs acting independently of AhR are poorly understood. In addition, PAHs often occur as mixtures that have non-additive or synergistic toxic effects, and the mechanisms behind these phenomena are still largely unknown. The risk assessment of PAHs is currently based on hypothesis that two action mechanisms, AhR-dependent, and non-polar narcosis, are taking place. The effect of mixtures is thought to be additive. However, as some non-AhR-agonistic PAHs cause heart-specific toxicity in developing fish, and many mixtures cause synergistic effects, the current risk assessment scheme is based on wrong hypotheses and therefore underestimates toxicity. As long as the mechanisms of AhR-independent and synergistic toxicity remain unresolved, it is difficult to include them in the risk assessment scheme. This project studies the molecular mechanisms and the etiology of the developmental toxicity caused by PAHs in fish. The objectives are 1) for the AhR-agonistic PAHs, to find out the downstream targets of AhR that explain the symptoms in the tissue and organism level; 2) to resolve the molecular mechanisms of toxicity of some PAHs that act independently of AhR; and 3) to explore the mechanisms behind the synergistic toxicity of PAHs. To accomplish this, salmonid yolk sac fry will be exposed to single PAHs with different modes of action, and their mixtures. As the cardiovascular tissue seems to be the target tissue for PAHs even with different molecular targets, the studies will concentrate on the heart and vasculature. Transcriptomics will be used in conjunction with proteomics, metabolomics, imaging, and studies on the location and metabolism of the compound in the organism, so that the pathways and networks affected by PAHs can be recognized and understood, and the mechanisms of toxicity followed from the molecular level to higher levels of biological organization. The results can be utilized in making the environmental risk assessment of PAHs more reliable

Principal Investigator

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