Pilot Metabolome-Wide Association Study of Benzo(a)pyrene in Serum From Military Personnel

Abstract

Objective A pilot study was conducted to test the feasibility of using Department of Defense Serum Repository (DoDSR) samples to study health and exposure-related effects. Methods Thirty unidentified human serum samples were obtained from the DoDSR and analyzed for normal serum metabolites with high-resolution mass spectrometry and serum levels of free benzo(a)pyrene (BaP) by gas chromatography-mass spectrometry. Metabolic associations with BaP were determined using a metabolome wide association study (MWAS) and metabolic pathway enrichment. Results The serum analysis detected normal ranges of glucose, selected amino acids, fatty acids, and creatinine. Free BaP was detected in a broad concentration range. MWAS of BaP showed associations with lipids, fatty acids, and sulfur amino acid metabolic pathways. Conclusion The results show the DoDSR samples are of sufficient quality for chemical profiling of DoD personnel.

Metabolic Pathways and Networks Associated With Tobacco Use in Military Personnel

“…For instance, arginine, tryptophan and other amino acids have been confirmed; acylcarnitines have been confirmed; sphinganine, urate and enzyme cofactors have been confirmed (17). PAH metabolites have been linked to authentic PAH measures by significance in metabolic correlation analyses (39). Thus, the overall evidence supports the conclusion that the central metabolic network structures that discriminate tobacco users from non-users is complex and not simply linked to biochemically defined metabolic pathways.…”

“…For instance, the carnitine pathway changes associated with tobacco use are also found in association with cadmium exposure (40) and in association with PAH levels in the blood [Walker et al this volume, (39)]. Several metabolic pathways changed with tobacco use, including arginine and proline metabolism, aspartate and asparagine metabolism, and uria cycle/amino group metabolism are also altered association with strenuous physical exercise condition (41).…”

Trends in the application of high-resolution mass spectrometry for human biomonitoring: An analytical primer to studying the environmental chemical space of the human exposome

“…Applications of HRMS to find associations between biomarkers of exposure and effect are discussed (Walker et al, 2016a). For example, anthracene concentrations in human sera were found to be significantly correlated with 24 and 18 adduct masses of polycyclic aromatic hydrocarbons metabolites from HRMS analysis coupled with HILIC and RP chromatography, respectively (Walker et al, 2016b). Other examples of relevance are in regards to the untargeted biomonitoring of pesticides exposure in humans (Roca et al, 2014) (Jamin et al, 2014).…”

Deployment-Associated Exposure Surveillance With High-Resolution Metabolomics

“…The ability of HRM to advance measurement of exposure biomarkers in human samples is highlighted in Figure 4A. In this analysis, quantified PAH levels of anthracene measured using GC-MS in 30 non-identified serum samples (6, 61) were tested for association with m/z ions detected by HRM matching known adduct masses of PAH metabolites from the KEGG database. Twenty-four metabolites detected using HILIC chromatography with positive electrospray ionization and 18 using reverse-phase chromatography with positive atmospheric chemical ionization (46) were found to be significantly associated with serum PAH levels, supporting the use of HRM for a more comprehensive measure of exposure biomarkers than available from targeted biomonitoring alone.…”

“…Previous studies have established the integrity of samples stored within the DoDSR (61, 77) and therefore highlight the opportunity for further advancement of the repository as an environmental health resource. The recent development of reference standardization (15) to obtain estimates of absolute concentrations of endogenous metabolites, health indicators and environmental chemicals, establishes an affordable approach.…”