Open AccessBiomonitoring of Ambient Outdoor Air Pollutant Exposure in Humans Using Targeted Serum Albumin Adductomics
Author(s) -
Joshua W. Smith,
Robert N. O’Meally,
Derek K. Ng,
Jian Guo Chen,
Thomas W. Kensler,
Robert N. Cole,
John D. Groopman
Publication year - 2021
Publication title -
chemical research in toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.031
H-Index - 156
eISSN - 1520-5010
pISSN - 0893-228X
DOI - 10.1021/acs.chemrestox.1c00055
Subject(s) - biomonitoring , chemistry , environmental chemistry , albumin , adduct , chromatography , biochemistry , organic chemistry
Outdoor air pollution, a spatially and temporally complex mixture, is a human carcinogen. However, ambient measurements may not reflect subject-level exposures, personal monitors do not assess internal dose, and spot assessments of urinary biomarkers may not recapitulate chronic exposures. Nucleophilic sites in serum albumin-particularly the free thiol at Cys 34 -form adducts with electrophiles. Due to the 4-week lifetime of albumin in circulation, accumulating adducts can serve as intermediate- to long-residence biomarkers of chronic exposure and implicate potential biological effects. Employing nanoflow liquid chromatography-high-resolution mass spectrometry (nLC-HRMS) and parallel reaction monitoring (PRM), we have developed and validated a novel targeted albumin adductomics platform capable of simultaneously monitoring dozens of Cys 34 adducts per sample in only 2.5 μL of serum, with on-column limits of detection in the low-femtomolar range. Using this platform, we characterized the magnitude and impact of ambient outdoor air pollution exposures with three repeated measurements over 84 days in n = 26 nonsmoking women ( n = 78 total samples) from Qidong, China, an area with a rising burden of lung cancer incidence. In concordance with seasonally rising ambient concentrations of NO 2 , SO 2 , and PM 10 measured at stationary monitors, we observed elevations in concentrations of Cys 34 adducts of benzoquinone ( p < 0.05), benzene diol epoxide (BDE; p < 0.05), crotonaldehyde ( p < 0.01), and oxidation ( p < 0.001). Regression analysis revealed significant elevations in oxidation and BDE adduct concentrations of 300% to nearly 700% per doubling of ambient airborne pollutant levels ( p < 0.05). Notably, the ratio of irreversibly oxidized to reduced Cys 34 rose more than 3-fold during the 84-day period, revealing a dramatic perturbation of serum redox balance and potentially serving as a portent of increased pollution-related mortality risk. Our targeted albumin adductomics assay represents a novel and flexible approach for sensitive and multiplexed internal dosimetry of environmental exposures, providing a new strategy for personalized biomonitoring and prevention.