Human Metabolic Responses to Chronic Environmental Polycyclic Aromatic Hydrocarbon Exposure by a Metabolomic Approach

Abstract

The toxicities of polycyclic aromatic hydrocarbons (PAHs) have been extensively explored due to their carcinogenic and mutagenic potency; however, little is known about the metabolic responses to chronic environmental PAH exposure among the general population. In the present study, 566 healthy volunteers were dichotomized into exposed and control groups to investigate PAH-induced perturbations in the metabolic profiles. Nine urine PAH metabolites were measured by a sensitive LC-MS/MS method to comprehensively evaluate the PAH exposure level of each individual, and the metabolic profiles were characterized via a LC-MS-based metabolomic approach. PAH exposure was correlated to its metabolic outcomes by linear and logistic regression analyses. Metabolites related to amino acid, purine, lipid, and glucuronic acid metabolism were significantly changed in the exposed group. 1-Hydroxyphenanthrene and dodecadienylcarnitine have potential as sensitive and reliable biomarkers for PAH exposure and its metabolic outcomes, respectively, in the general population. These findings generally support the hypothesis that environmental PAH exposure causes oxidative stress-related effects in humans. The current study provides new insight into the early molecular events induced by PAH exposure in the actual environment.

Particulate metal exposures induce plasma metabolome changes in a commuter panel study

“…In contrast, hs-CRP has been reported to be at most minimally associated with time of day [ 47 , 48 ]. Repeated measures and contrasting exposures within study participants was a strength where changes in measurements over time can be explored with partitioning of inter- and intra-individual variability [ 49 ], and may have provided analytical improvement over cross-sectional analyses for causal inference [ 9 ].…”

“…Environmental metabolomics has emerged as an approach for sensitively quantitating thousands of chemical signals in a biological sample, providing broad spectrum measurements of human metabolism that may be indicative of environmental chemicals [ 8 ]. Metabolomic perturbations have been associated with occupational air pollution exposures [ 9 , 10 ]. Walker, et al, employed high-resolution metabolomics (HRM), using sensitive liquid chromatography-mass spectrometry (LC-MS), coupled with advanced bioinformatics methods, as a platform linking exposure to internal doses and biological responses.…”

Exposure to polycyclic aromatic hydrocarbons and volatile organic compounds among recently pregnant rural Guatemalan women cooking and heating with solid fuels

“…The biological mechanisms by which PAH and VOC metabolites exert effects on health outcomes are not well established but they have been shown to induce oxidative stress (Li et al, 2015; Wang et al, 2015). Two urinary markers of oxidative stress are 8-isoprostane, a measure of lipid peroxidation (Milne et al, 2005), and 8-hydroxy-2′-deoxyguanosine (8-OHdG), a measure of DNA oxidation (Evans et al, 2010; Poulsen et al, 2014).…”

Urinary polycyclic aromatic hydrocarbons and measures of oxidative stress, inflammation and renal function in adolescents: NHANES 2003–2008

“…Interestingly, three studies reported evidence of potential PAH-related oxidative stress in children. A cross-sectional multicity study of schoolchildren in China and South Korea, reported an association between PAH exposure marker 1-hydroxypyrene and urinary malondialdehyde (MDA), a marker of oxidative stress (23), while a study of metabolomics responses to PAH exposure, which included children in the study population, found that PAH exposure was associated with altered markers of oxidative stress (24). A recent study observed a significant dose response relationship between the sum concentration of urinary monohydroxylated metabolites of PAHs and 8-hydroxy-2-deoxyguanosine (8-OHdG), a common biomarker of oxidative stress (25).…”