Dataset Information

Profiling the Serum Albumin Cys34 Adductome of Solid Fuel Users in Xuanwei and Fuyuan, China.

ABSTRACT: Xuanwei and Fuyuan counties in China have the highest lung cancer rates in the world due to household air pollution from combustion of smoky coal for cooking and heating. To discover potential biomarkers of indoor combustion products, we profiled adducts at the Cys34 locus of human serum albumin (HSA) in 29 nonsmoking Xuanwei and Fuyuan females who used smoky coal, smokeless coal, or wood and 10 local controls who used electricity or gas fuel. Our untargeted "adductomics" method detected 50 tryptic peptides of HSA, containing Cys34 and prominent post-translational modifications. Putative adducts included Cys34 oxidation products, mixed disulfides, rearrangements, and truncations. The most significant differences in adduct levels across fuel types were observed for S-glutathione (S-GSH) and S-?-glutamylcysteine (S-?-GluCys), both of which were present at lower levels in subjects exposed to combustion products than in controls. After adjustment for age and personal measurements of airborne benzo(a)pyrene, the largest reductions in levels of S-GSH and S-?-GluCys relative to controls were observed for users of smoky coal, compared to users of smokeless coal and wood. These results point to possible depletion of GSH, an essential antioxidant, and its precursor ?-GluCys in nonsmoking females exposed to indoor-combustion products in Xuanwei and Fuyuan, China.

SUBMITTER: Lu SS

PROVIDER: S-EPMC5567851 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Profiling the Serum Albumin Cys34 Adductome of Solid Fuel Users in Xuanwei and Fuyuan, China.

Lu Sixin S SS Grigoryan Hasmik H Edmands William M B WM Hu Wei W Iavarone Anthony T AT Hubbard Alan A Rothman Nathaniel N Vermeulen Roel R Lan Qing Q Rappaport Stephen M SM

Environmental science & technology 20161212 1

Xuanwei and Fuyuan counties in China have the highest lung cancer rates in the world due to household air pollution from combustion of smoky coal for cooking and heating. To discover potential biomarkers of indoor combustion products, we profiled adducts at the Cys34 locus of human serum albumin (HSA) in 29 nonsmoking Xuanwei and Fuyuan females who used smoky coal, smokeless coal, or wood and 10 local controls who used electricity or gas fuel. Our untargeted "adductomics" method detected 50 tryp ...[more]

PMID: 27936627

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Project description:BackgroundXuanwei and Fuyuan counties in Yunnan Province, China have among the highest lung cancer rates in the country. This has been associated with the domestic combustion of bituminous coal (referred to as "smoky" coal). Additionally, significant geographical variation in cancer rates among smoky coal users has been observed, suggesting heterogeneity in fuel source composition and/or combustion characteristics. Research thus far has indicated that smoky coal emits high levels of polycyclic aromatic hydrocarbons (PAHs) and contains high concentrations of fine grained crystalline quartz, however, much of this research is limited in terms of sample size and geographic scope. In order to more fully characterise geochemical and elemental compositions of smoky and smokeless coal use in Xuanwei and Fuyuan, we carried out a large exposure assessment study in households in this region.MethodsFuel samples representing smoky and "smokeless" (anthracite, the major alternative coal type in the region) coals were collected from 137 homes in Xuanwei and Fuyuan. Rock-Eval, Leco-CS, XRF analysis and electron microscopy were used to establish hydrocarbon content (to represent volatile organic compounds), major and trace element composition and mineral composition respectively. Heterogeneity in coal characteristics between and within coal types was assessed by the Kruskal-Wallis test.Results145 coal samples (116 smoky and 29 smokeless coals) were analysed. Statistically significant differences between smoky and smokeless coals with regard to hydrocarbon content, sulfur, trace elements and mineral composition were observed. Of note, smoky coal contained between 5 and 15 times the amount of volatile organic matter and twice the amount of quartz (including respirable quartz) than smokeless coal. Smoky coal generally had lower levels of trace elements (plus aluminium) than smokeless coal. Significant variation was also observed between smoky coal samples from different geographical areas with regard to hydrocarbon content and elemental composition (including aluminium and silicon).DiscussionThis paper has identified compositional differences between and within smoky and smokeless coals sourced from Xuanwei and Fuyuan counties. A decreased ratio of aluminium to silicon in smoky coal suggests elevated free silica, a finding consistent with observed higher levels of quartz. Elevated volatile organic matter content in smoky coal (when compared to smokeless coal) is consistent with the geochemical expectations for smoky and smokeless coals. These findings also reflect previous observations of elevated volatile compound emissions (notably PAHs) from smoky coal in the area. The observed heterogeneity in coal composition between and within coal types may provide leads to the observed heterogeneity in cancer risk observed in this area.

Project description:Background: Increasing evidence suggests that exposure to air pollution during pregnancy is associated with adverse pregnancy outcomes. However, biomarkers associated with air pollution exposure are widely lacking and often transient. In addition, ascertaining biospecimens during pregnacy to assess the prenatal environment remains largely infeasible. Objectives: To address these challenges, we investigated relationships between air pollution exposure during pregnancy and human serum albumin Cys34 (HSA-Cys34) adducts in newborn dried blood spots (DBS) samples, which captures an integration of perinatal exposures to small reactive molecules in circulating blood. Methods: Newborn DBS were obtained from a state archive for a cohort of 120 children born at one Kaiser Permanente Southern California (KPSC) hospitals in 2007. These children were selected to maximize the range of residential air pollution exposure during the entire pregnancy to PM2.5, PM10, NO2, O3, based on monthly estimates interpolated from regulatory monitoring sites. HSA-Cys34 adducts were selected based on previously reported relationships with air pollution exposure and oxidative stress. Results: Six adducts measured in newborn DBS samples were associated with air pollution exposures during pregnancy; these included direct oxidation products, adducts formed with small thiol compounds, and adducts formed with reactive aldehydes. Two general trends were identified: Exposure to air pollution late in pregnancy (i.e., in the last 30 days) was associated with increased oxidative stress, and exposure to air pollution earlier in pregnancy (i.e., not in the last 30 days) was associated with decreased oxidative stress around the time of birth. Discussion: Air pollution exposure occurring during pregnancy can alter biology and leave measurable impacts on the developing infant captured in the newborn DBS adductome, which represents a promising tool for investigating adverse birth outcomes in population-based studies.

Project description:BackgroundLung cancer rates among never-smoking women in Xuanwei and Fuyuan in China are among the highest in the world and have been attributed to the domestic use of smoky (bituminous) coal for heating and cooking. However, the key components of coal that drive lung cancer risk have not been identified.ObjectivesWe aimed to investigate the relationship between lifelong exposure to the constituents of smoky coal (and other fuel types) and lung cancer.MethodsUsing a population-based case-control study of lung cancer among 1,015 never-smoking female cases and 485 controls, we examined the association between exposure to 43 household air pollutants and lung cancer. Pollutant predictions were derived from a comprehensive exposure assessment study, which included methylated polycyclic aromatic hydrocarbons (PAHs), which have never been directly evaluated in an epidemiological study of any cancer. Hierarchical clustering and penalized regression were applied in order to address high colinearity in exposure variables.ResultsThe strongest association with lung cancer was for a cluster of 25 PAHs [odds ratio (OR): 2.21; 95% confidence interval (CI): 1.67, 2.87 per 1 standard deviation (SD) change], within which 5-methylchrysene (5-MC), a mutagenic and carcinogenic PAH, had the highest individual observed OR (5.42; 95% CI: 0.94, 27.5). A positive association with nitrogen dioxide ([Formula: see text]) was also observed (OR: 2.06; 95% CI: 1.19, 3.49). By contrast, neither benzo(a)pyrene (BaP) nor fine particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text]) were associated with lung cancer in the multipollutant models.ConclusionsTo our knowledge, this is the first study to comprehensively evaluate the association between lung cancer and household air pollution (HAP) constituents estimated over the entire life course. Given the global ubiquity of coal use domestically for indoor cooking and heating and commercially for electric power generation, our study suggests that more extensive monitoring of coal combustion products, including methylated PAHs, may be warranted to more accurately assess health risks and develop prevention strategies from this exposure. https://doi.org/10.1289/EHP4913.

Dataset Information

Profiling the Serum Albumin Cys34 Adductome of Solid Fuel Users in Xuanwei and Fuyuan, China.

Publications

Profiling the Serum Albumin Cys34 Adductome of Solid Fuel Users in Xuanwei and Fuyuan, China.

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