Evaluating changes in firefighter urinary metabolomes after structural fires: an untargeted, high resolution approach

• Type of Material: Article
• Authors: Melissa A. Furlong, University of Arizona, Tucson; Tuo Liu, University of Arizona, Tucson; Justin M. Snider, University of Arizona, Tucson; Malak M. Tfaily, University of Arizona, Tucson; Christian Itson, University of Arizona, Tucson; Shawn Beitel, University of Arizona, Tucson; Krishna Parsawar, University of Arizona, Tucson; Kristen Keck, University of Arizona, Tucson; James Galligan, University of Arizona, Tucson; Douglas Walker, Emory University; John J. Gulotta, Tucson Fire Department; Jefferey L. Burgess, University of Arizona, Tucson
• Language: English
• Date: 2023-11-27
• Publisher: Springer Nature
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2023
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1038/s41598-023-47799-x
• Title of Journal or Parent Work: Scientific Reports
• Volume: 13
• Start Page: 20872
• Grant/Funding Information: Research reported in this publication was supported, in part, by the National Cancer Institute of the National Institutes of Health under award number P30 CA023074, as well as FEMA funding (EMW-2014-FP-00200), and funding from the National Institute of Environmental Health Sciences (NIEHS) R00ES028743, P30 ES006694, T32 ES007091, P30CA023074.
• Keywords: Metabolomics; Risk factors
• Research Categories: Health Sciences, Public Health; Health Sciences, Occupational Health and Safety; Chemistry, Biochemistry; Health Sciences, Toxicology; Health Sciences, Epidemiology

Abstract

Firefighters have elevated rates of urinary tract cancers and other adverse health outcomes, which may be attributable to environmental occupational exposures. Untargeted metabolomics was applied to characterize this suite of environmental exposures and biological changes in response to occupational firefighting. 200 urine samples from 100 firefighters collected at baseline and two to four hours post-fire were analyzed using untargeted liquid-chromatography and high-resolution mass spectrometry. Changes in metabolite abundance after a fire were estimated with fixed effects linear regression, with false discovery rate (FDR) adjustment. Partial least squares discriminant analysis (PLS-DA) was also used, and variable important projection (VIP) scores were extracted. Systemic changes were evaluated using pathway enrichment for highly discriminating metabolites. Metabolome-wide-association-study (MWAS) identified 268 metabolites associated with firefighting activity at FDR q < 0.05. Of these, 20 were annotated with high confidence, including the amino acids taurine, proline, and betaine; the indoles kynurenic acid and indole-3-acetic acid; the known uremic toxins trimethylamine n-oxide and hippuric acid; and the hormone 7a-hydroxytestosterone. Partial least squares discriminant analysis (PLS-DA) additionally implicated choline, cortisol, and other hormones. Significant pathways included metabolism of urea cycle/amino group, alanine and aspartate, aspartate and asparagine, vitamin b3 (nicotinate and nicotinamide), and arginine and proline. Firefighters show a broad metabolic response to fires, including altered excretion of indole compounds and uremic toxins. Implicated pathways and features, particularly uremic toxins, may be important regulators of firefighter’s increased risk for urinary tract cancers.