Integrated Screening of Bioactive Contaminants Contributing to the High Receptor Activities in St. Lawrence Beluga Whales

Holly Barrett, Jonathan Verreault, Magali Houde, Frank Wania, Hui Peng 

While elevated tissue concentrations of pollutants have been reported in St. Lawrence Estuary (SLE) belugas, the exact bioactive chemicals exerting toxicity remain unknown. We integrated chemical analysis and receptor activity screening to identify contaminants of potential toxicity in SLE beluga liver and blubber and reference Arctic beluga blubber. 
Contaminants were extracted from pooled tissue of whales found stranded from 1990-2017. Extracts were analyzed by mass spectrometry, and results were matched to an online database of bioactive chemicals (Tox21). ~200 matched compounds were significantly more abundant in SLE tissue than Arctic tissue. Extracts were tested for their activity towards the AhR receptor (a protein which mediates toxicity) to investigate the contribution of chemicals towards AhR-mediated responses, and significant responses were detected (e.g., 0.16 g/mL liver induced AhR). Consistent with the more diverse chemical burden found in SLE belugas, SLE tissue exerted significantly higher AhR activity than Arctic blubber. Several AhR-active compounds detected by Tox21 screening partially explained the SLE activity (e.g., natural indoles, synthetic dyes). Extracts were then screened against a suite of 48 human nuclear receptors (NRs; proteins regulating physiological processes such as disease), revealing significant activities for several NRs. Distinct from Arctic blubber, SLE extracts exerted significant activity towards several NRs with functions in cancer progression. Multiple NR-active chemicals were detected by Tox21 database matching including hydrocarbon surfactants. These results mark the first time that receptor activity has been measured for SLE belugas.

Inspired by the detection of numerous bioactive compounds in pooled tissue, we further screened SLE tissues from individual specimens collected in different years. Preliminary results confirmed the detection of numerous cosmetic dye-related compounds in SLE tissue, which were enriched in 2015 liver relative to 2005 liver, indicating possible accumulation in tissue over time. Additionally, a suite of hydrocarbon surfactants, a common component in personal care products (PCPs), was confirmed in the tissues. The presence of these compounds may result from consumer use or the manufacturing of cosmetics and PCPs along the St. Lawrence. Ongoing work focuses on reporting the temporal trends of such compounds in SLE tissue from 2000-2017.