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Using Biomarkers to Characterize Exp...

Lu, Sixin Samantha,

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Using Biomarkers to Characterize Exposures to Diesel Exhaust and Smoky Coal /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Using Biomarkers to Characterize Exposures to Diesel Exhaust and Smoky Coal // Sixin Samantha Lu.
Author:	Lu, Sixin Samantha,
Description:	1 electronic resource (65 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 86-03, Section: B.
Contained By:	Dissertations Abstracts International86-03B.
Subject:	Toxicology. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10237506
ISBN:	9798384446675

Using Biomarkers to Characterize Exposures to Diesel Exhaust and Smoky Coal /
Lu, Sixin Samantha,

Using Biomarkers to Characterize Exposures to Diesel Exhaust and Smoky Coal /Sixin Samantha Lu. - 1 electronic resource (65 pages)

Source: Dissertations Abstracts International, Volume: 86-03, Section: B.

Ambient air pollution and household air pollution are among the leading causes of mortality, responsible for 6 million premature deaths per year globally. The combustion of fossil fuels, including diesel and coal, constitutes a major source of air pollution. Polycyclic aromatic hydrocarbons (PAHs) are a group of compounds released during incomplete combustion of organic material which has been classified as carcinogenic to humans. Inhalational exposure to combustion emissions can be quantitated either externally such as by determining personal airborne PAH levels, or internally by determining the levels of a biomarker in the exposed population. Given the ease of sample collection, identifying suitable urine and blood biomarkers that accurately reflect exposure to air pollution is of significant interest. This dissertation examines the relations of the levels of biomarkers in urine and plasma with exposure determinants and with personal airborne measurements in humans exposed to emissions from diesel and solid fuel combustion. First, urinary PAH levels were measured using headspace solid-phase microextraction and gas chromatography-mass spectrometry in 28 nonsmokers in two studies before, immediately after and the day after short-term, controlled exposures to diesel exhaust (DE). Likelihood-ratio tests on linear mixed-effects models indicated that, after adjusting for other covariates, DE exposure did not significantly alter urinary PAH levels. Second, urinary PAH levels were reported in 163 Chinese female nonsmokers from Xuanwei and Fuyuan counties, where the highest lung cancer rates in the world are observed due to household air pollution from combustion of smoky coal. Mixed-effects models revealed that personal airborne PAH levels (over a wide range of exposure up to occupational levels experienced by coke oven workers), age and exposure characteristics such as fuel and stove types were significant predictors of urinary PAH levels. Third, using an untargeted nanoflow liquid chromatography and high-resolution mass spectrometry method, 50 adducts were detected at the nucleophilic Cys34 locus of human serum albumin (HSA) in 29 of the aforementioned Xuanwei and Fuyuan women and 10 local controls. Upon adduct annotation and quantitation, Wilcoxon rank sum tests showed that levels of S-glutathione (S-GSH) and S-γ-glutamylcysteine (S-γ-GluCys), adducts related to glutathione, an important antioxidant, were lower in exposed subjects compared to those in controls. After adjustment for age and personal measurements of airborne benzo(a)pyrene (a representative carcinogenic PAH) using multivariate regressions, the largest reductions in levels of S-GSH and S-γ-GluCys relative to controls were observed for smoky coal users, compared to users of smokeless coal and wood. These studies collectively demonstrate that urinary unmetabolized PAHs may be suitable biomarkers of wide-ranging exposures to fuel combustion emissions and that Cys34 adductomics is a promising tool for discovering biomarkers of longer-term exposures, owing to the one-month residence time of HSA.

English

ISBN: 9798384446675Subjects--Topical Terms:

556884
Toxicology.
Subjects--Index Terms:

Biomarkers

Using Biomarkers to Characterize Exposures to Diesel Exhaust and Smoky Coal /
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500 $a Advisors: Rappaport, Stephen M. Committee members: Smith, Martyn T.; Williams, Evan.
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520 $a Ambient air pollution and household air pollution are among the leading causes of mortality, responsible for 6 million premature deaths per year globally. The combustion of fossil fuels, including diesel and coal, constitutes a major source of air pollution. Polycyclic aromatic hydrocarbons (PAHs) are a group of compounds released during incomplete combustion of organic material which has been classified as carcinogenic to humans. Inhalational exposure to combustion emissions can be quantitated either externally such as by determining personal airborne PAH levels, or internally by determining the levels of a biomarker in the exposed population. Given the ease of sample collection, identifying suitable urine and blood biomarkers that accurately reflect exposure to air pollution is of significant interest. This dissertation examines the relations of the levels of biomarkers in urine and plasma with exposure determinants and with personal airborne measurements in humans exposed to emissions from diesel and solid fuel combustion. First, urinary PAH levels were measured using headspace solid-phase microextraction and gas chromatography-mass spectrometry in 28 nonsmokers in two studies before, immediately after and the day after short-term, controlled exposures to diesel exhaust (DE). Likelihood-ratio tests on linear mixed-effects models indicated that, after adjusting for other covariates, DE exposure did not significantly alter urinary PAH levels. Second, urinary PAH levels were reported in 163 Chinese female nonsmokers from Xuanwei and Fuyuan counties, where the highest lung cancer rates in the world are observed due to household air pollution from combustion of smoky coal. Mixed-effects models revealed that personal airborne PAH levels (over a wide range of exposure up to occupational levels experienced by coke oven workers), age and exposure characteristics such as fuel and stove types were significant predictors of urinary PAH levels. Third, using an untargeted nanoflow liquid chromatography and high-resolution mass spectrometry method, 50 adducts were detected at the nucleophilic Cys34 locus of human serum albumin (HSA) in 29 of the aforementioned Xuanwei and Fuyuan women and 10 local controls. Upon adduct annotation and quantitation, Wilcoxon rank sum tests showed that levels of S-glutathione (S-GSH) and S-γ-glutamylcysteine (S-γ-GluCys), adducts related to glutathione, an important antioxidant, were lower in exposed subjects compared to those in controls. After adjustment for age and personal measurements of airborne benzo(a)pyrene (a representative carcinogenic PAH) using multivariate regressions, the largest reductions in levels of S-GSH and S-γ-GluCys relative to controls were observed for smoky coal users, compared to users of smokeless coal and wood. These studies collectively demonstrate that urinary unmetabolized PAHs may be suitable biomarkers of wide-ranging exposures to fuel combustion emissions and that Cys34 adductomics is a promising tool for discovering biomarkers of longer-term exposures, owing to the one-month residence time of HSA.
546 $a English
590 $a School code: 0028
650 4 $a Toxicology. $3 556884
650 4 $a Environmental health. $3 543032
650 4 $a Public health. $3 534748
653 $a Biomarkers
653 $a Diesel exhaust
653 $a Air pollution
653 $a Human serum albumin
653 $a Polycyclic aromatic hydrocarbons
653 $a Smoky coal
653 $a Urine
690 $a 0383
690 $a 0470
690 $a 0573
710 2 $a University of California, Berkeley. $b Molecular Toxicology. $e degree granting institution. $3 3828434
720 1 $a Rappaport, Stephen M. $e degree supervisor.
773 0 $t Dissertations Abstracts International $g 86-03B.
790 $a 0028
791 $a Ph.D.
792 $a 2024
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10237506