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Nicklisch, SCT, Rees SD, McGrath AP, Gökirmak T, Bonito LT, Vermeer LM, Cregger C, Loewen G, Sandin S, Chang G, Hamdoun A.  2016.  Global marine pollutants inhibit P-glycoprotein: Environmental levels, inhibitory effects, and cocrystal structure. Science Advances. 2   10.1126/sciadv.1600001   Abstract

The world’s oceans are a global reservoir of persistent organic pollutants to which humans and other animals are exposed. Although it is well known that these pollutants are potentially hazardous to human and environmental health, their impacts remain incompletely understood. We examined how persistent organic pollutants interact with the drug efflux transporter P-glycoprotein (P-gp), an evolutionarily conserved defense protein that is essential for protection against environmental toxicants. We identified specific congeners of organochlorine pesticides, polychlorinated biphenyls, and polybrominated diphenyl ethers that inhibit mouse and human P-gp, and determined their environmental levels in yellowfin tuna from the Gulf of Mexico. In addition, we solved the cocrystal structure of P-gp bound to one of these inhibitory pollutants, PBDE (polybrominated diphenyl ether)–100, providing the first view of pollutant binding to a drug transporter. The results demonstrate the potential for specific binding and inhibition of mammalian P-gp by ubiquitous congeners of persistent organic pollutants present in fish and other foods, and argue for further consideration of transporter inhibition in the assessment of the risk of exposure to these chemicals.

Nicklisch, SCT, Bonito LT, Sandin S, Hamdoun A.  2017.  Geographic differences in persistent organic pollutant levels of yellowfin tuna. Environ Health Perspect. 125:067014.   10.1289/ehp518   Abstract

BACKGROUND: Fish are a source of persistent organic pollutants (POPs) in the human diet. Although species, trophic level, and means of production are typically considered in predicting fish pollutant load, and thus recommendations of consumption, capture location is usually not accounted for. OBJECTIVES: Yellowfin tuna (Thunnus albacares) are harvested from across the world's oceans and are widely consumed. Here, we determined geographic variation in the overall mass, concentration, and composition of POPs in yellowfin and examined the differences in levels of several POP congeners of potential relevance to human health. METHODS: We sampled dorsal muscle of 117 yellowfin tuna from 12 locations worldwide, and measured POP levels using combined liquid or gas chromatography and mass spectrometry according to U.S. Environmental Protection Agency standard procedures. RESULTS: POP levels varied significantly among sites, more than 36-fold on a mass basis. Individual fish levels ranged from 0.16 to wet weight and lipid-normalized concentrations from . Levels of 10 congeners that interfere with the cellular defense protein P-glycoprotein, termed transporter interfering compounds (TICs), ranged from 0.05 to wet weight and from in tuna lipid. Levels of TICs, and their individual congeners, were strongly associated with the overall POP load. Risk-based analysis of several carcinogenic POPs indicated that the fish with the highest levels of these potentially harmful compounds were clustered at specific geographic locations. CONCLUSIONS: Capture location is an important consideration when assessing the level and risk of human exposure to POPs through ingestion of wild fish.

Nicklisch, SCT, Bonito LT, Sandin S, Hamdoun A.  2017.  Mercury levels of yellowfin tuna (Thunnus albacares) are associated with capture location. Environmental Pollution. 229:87-93.   10.1016/j.envpol.2017.05.070   AbstractWebsite

Mercury is a toxic compound to which humans are exposed by consumption of fish. Current fish consumption advisories focus on minimizing the risk posed by the species that are most likely to have high levels of mercury. Less accounted for is the variation within species, and the potential role of the geographic origin of a fish in determining its mercury level. Here we surveyed the mercury levels in 117 yellowfin tuna caught from 12 different locations worldwide. Our results indicated significant variation in yellowfin tuna methylmercury load, with levels that ranged from 0.03 to 0.82 mu g/g wet weight across individual fish. Mean mercury levels were only weakly associated with fish size (R-2 < 0.1461) or lipid content (R-2 < 0.00007) but varied significantly, by a factor of 8, between sites. The results indicate that the geographic origin of fish can govern mercury load, and argue for better traceability of fish to improve the accuracy of exposure risk predictions. (C)2017 Elsevier Ltd. All rights reserved.