Date/Time
Date(s) - 03/06/2022
1:30 pm - 2:30 pm

High Throughput Exposomic Studies for NewInsights into Smoke Exposures in Occupational and Population Health 

Date:                    Friday,June 3^rd, 2022

Time:                    1:30p.m.   

Zoom:                   available from fehert@mcmaster.ca

Host:                    Dr.Philip Britz-McKibbin

Abstract:     

    Exposomics aims to characterize the totality of exposures over an individual’slifetime, and their impact on human health. Currently, chronic exposure toharmful chemicals from air pollution and/or tobacco smoke, along with asuboptimal diet, remain leading causes for preventable mortality and morbidityworldwide. As a result, new analytical methods are needed to measure robustbiomarkers of smoke exposure for improved risk assessment of clinical events.This thesis aims to develop high throughput methods to rapidly quantify urinarybiomarkers of environmental smoke in high-risk occupations, and diverse globalpopulations using multisegment injection-capillary electrophoresis-massspectrometry (MSI-CE-MS) technology. Chapter II outlines aninter-laboratory method comparison for the targeted analysis of urinary1-hydroxypyrene (HP) when using gas chromatography-high resolution massspectrometry (GC-HRMS) and liquid chromatography-tandem mass spectrometry(LC-MS/MS) on urine samples collected from firefighters. This work revealed thecritical role of incomplete enzymatic deconjugation on method bias andunderreporting of true smoke exposures. Chapter III introduces a highthroughput MSI-CE-MS/MS method (< 3 min/sample) to directly analyze theintact glucuronide conjugate of HP (HP-G) in urine without complex pre-columnenzyme deconjugation and derivatization procedures. Importantly, firefightersdeployed under emergency conditions at the 2016 Fort McMurray wildfire hadcreatinine normalized HP-G concentrations that fell below the biologicalexposure index, likely caused by delays in urine collection under emergencyconditions, at early stages of firefighting. Chapter IV extends fromtargeted biomonitoring of occupational smoke exposure, towards elucidating therelative risk of tobacco smoking in an international cohort of participants (n=1000)from the Prospective Urban and Rural Epidemiological (PURE) study.Comprehensive analysis of nicotine metabolites in urine by MSI-CE-MS allowedfor reliable determination of the total nicotine equivalent and nicotinemetabolic ratio as robust indicators of recent tobacco smoke exposure andnicotine dependence, respectively. This method offers a more accurate approachfor biochemical verification of smoking status in large-scale epidemiologicalstudies that are prone to bias and misreporting when relying on standardizedquestionnaires. Lastly, Chapter V employs a nontargeted metabolomicsworkflow using MSI-CE-MS to identify urinary metabolites that may serve asobjective dietary biomarkers of food intake in participants across 14 differentcountries from the PURE cohort. A panel of robust and generalizable metaboliteswere validated for biomonitoring of complex dietary exposures, that may furtherexacerbate the hazards of tobacco smoking. In summary, this thesis contributeshigh throughput analytical tools for characterizing the human urine exposome tobetter decipher the roles of smoke exposure, and suboptimal diet on chronicdisease burden among diverse populations and regions worldwide.