POPs are lipophilic chemical pollutants that accumulate in fat tissue of organisms when they are exposed. Marine mammals are particularly at risk of high xenobiotic accumulation. POPs can trigger xenobiotic responses meant to metabolise the chemicals, reduce their toxicity and enable their export, but this can make even more reactive products. The AHR pathway is one of the most studied of such systems in toxicology and associated with many AOPs. Expression of AHR-target genes has been found to be repressed in fibroblast cells that are increasingly being used as cell models for marine mammals. This thesis assesses the use of TSA using its role as a HDAC inhibitor to activate AHR-target genes and widen the application of fibroblasts as a cell model to identify AHR ligands using long finned pilot whale and polar bear cell cultures. TSA was found to significantly increase the gene activation of CYP1A1 by AHR ligands in polar bears. Although CYP1A1 was found to be induced naturally by ligands independently of TSA. This is in contrast to pilot whales where CYP1A1 was found to be epigenetically repressed. TSA shows potential to improve pilot whale fibroblasts as a cell model in AHR agonist identification.
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