Abstract: A complicating factor in environmental contaminant research is that many commercial and industrial compounds are metabolically labile, transforming to produce environmentally persistent and/or bioactive compounds. Therefore, the sources of exposure to environmental contaminants can stem from the direct use, but also indirectly, from metabolically active precursor compounds. While contaminant biotransformation pathways have been elucidated in several organisms, we address the following questions: which enzymes contribute to contaminant bioactivation? What is the propensity for metabolism to occur in extrahepatic systems? Can the organism’s response to toxicant exposure be measured by monitoring several classes of endogenous signalling molecules? This talk will focus on three of our research projects that center on addressing these questions. The first characterizes the oxidative enzymes responsible for transforming a class of polyfluoroalkyl substances (PFASs), the fluorotelomer alcohols (FTOHs), into persistent organic pollutants. For this, we used a variety of in vitro tools to characterize the contribution of six major xenobiotic metabolizing enzymes at metabolizing FTOH oxidation. The second covers the development of a Caenorhabditis elegans model to measure oxidative stress, pairing traditional methods with a targeted LC-MS/MS method to measure over 60 signalling lipids involved in numerous physiological and pathological processes. The third examines the contribution of the gut microbiome as an important site of biotransformation, using a PFAS surfactant as a representative metabolically labile contaminant. Capturing biotransformation catalyzed by enzymes within the gut microbiome is important given the potential to increase circulating levels of bioactive metabolites, which cannot be elucidated by traditional hepatic metabolic studies.
Bibliography: Amy Rand is an Assistant Professor in the Department of Chemistry and Institute of Biochemistry at Carleton University. Prior to joining the faculty at Carleton, she was a postdoctoral fellow within the Comprehensive Cancer Centre at UC Davis and has a Ph.D. in Environmental Chemistry from the University of Toronto. Her primary research interests are studying human exposure sources of environmental contaminants and understanding the mechanisms by which they transform into more active toxicants. She is also interested in how contaminant exposure affects oxidized lipid signalling, and the interaction between different kinds of environmental stressors (e.g., diet) that may alter relationships between contaminant exposure and their toxic response.