Identification of aryl hydrocarbon receptor (AhR)-active metabolites in firefighter urine samples

Abstract

Firefighter (FF) cancer rates are elevated due to chemical exposures, with strong evidence for contribution of receptor-mediated effects which are not adequately accounted for by known carcinogens. The aryl hydrocarbon receptor (AhR) is a protein best known for its role in mediating toxicity from dioxin-like compounds. Here we used an untargeted metabolomics approach to investigate whether the increased AhR mediated response observed in post-fire urine samples would reveal AhR ligands previously not associated with FF occupational exposure. Analysis of hydrophilic interaction liquid chromatography (HILIC) negative and reverse phase (RP) positive metabolomic data from three fractionated post-fire urine samples having elevated AhR activity revealed 27 metabolites in FF samples compared to one non-FF sample. These metabolites belonged to a wide range of chemical classes such as indoles and aromatic ketones. Further investigation into the roles of these 27 metabolites in AhR mediation might help elucidate the biochemical pathways leading to elevated cancer risk in FFs.