Adaptive Stress Response Pathways Induced by Environmental Mixtures of Bioaccumulative Chemicals in Dugongs

• Published in: Environmental science & technology Vol. 49; no. 11; pp. 6963 - 6973
• Main Authors: Jin, Ling, Gaus, Caroline, Escher, Beate I.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 02.06.2015
• Subjects: Activation, Metabolic - drug effects; Adaptation, Physiological - drug effects; Animal Structures - drug effects; Animal Structures - metabolism; Animals; Bioaccumulation; Bioassays; Biological Assay; blubber; Dioxins - toxicity; DNA damage; Dugong; Dugong - metabolism; Environmental Monitoring; Environmental Pollutants - toxicity; enzymes; inflammation; lipids; liver; Marine; Marine mammals; mechanism of action; Metabolism; NF-E2-Related Factor 2 - metabolism; Oxidative stress; Oxidative Stress - drug effects; polychlorinated dibenzodioxins; Polychlorinated Dibenzodioxins - analogs & derivatives; Polychlorinated Dibenzodioxins - toxicity; Rats; Receptors, Aryl Hydrocarbon - metabolism; Stress response; Stress, Physiological - drug effects; Toxicity; Toxicology; wildlife; xenobiotics
• ISSN: 0013-936X; 1520-5851; 1520-5851
• DOI: 10.1021/acs.est.5b00947

To address the poorly understood mixture effects of chemicals in the marine mammal dugong, we coupled equilibrium-based passive sampling in blubber to a range of in vitro bioassays for screening mixtures of bioaccumulative chemicals. The modes of action included early effect indicators along important toxicity pathways, such as induction of xenobiotic metabolism, and some integrative indicators downstream of the molecular initiating event, such as adaptive stress responses. Activation of aryl hydrocarbon receptor (AhR) and Nrf2-mediated oxidative stress response were found to be the most prominent effects, while the p53-mediated DNA damage response and NF-κB-mediated response to inflammation were not significantly affected. Although polychlorinated dibenzo-p-dioxins (PCDDs) quantified in the samples accounted for the majority of AhR-mediated activity, PCDDs explained less than 5% of the total oxidative stress response, despite their known ability to activate this pathway. Altered oxidative stress response was observed with both individual chemicals and blubber extracts subject to metabolic activation by rat liver S9 fraction. Metabolic activation resulted in both enhanced and reduced toxicity, suggesting the relevance and utility of incorporating metabolic enzymes into in vitro bioassays. Our approach provides a first insight into the burden of toxicologically relevant bioaccumulative chemical mixtures in dugongs and can be applied to lipid tissue of other wildlife species.