Dataset Information

Exposure to diesel engine exhaust and alterations to the Cys34/Lys525 adductome of human serum albumin.

ABSTRACT: We investigated whether exposure to carcinogenic diesel engine exhaust (DEE) was associated with altered adduct levels in human serum albumin (HSA) residues. Nano-liquid chromatography-high resolution mass spectrometry (nLC-HRMS) was used to measure adducts of Cys34 and Lys525 residues in plasma samples from 54 diesel engine factory workers and 55 unexposed controls. An untargeted adductomics and bioinformatics pipeline was used to find signatures of Cys34/Lys525 adductome modifications. To identify adducts that were altered between DEE-exposed and unexposed participants, we used an ensemble feature selection approach that ranks and combines findings from linear regression and penalized logistic regression, then aggregates the important findings with those determined by random forest. We detected 40 Cys34 and 9 Lys525 adducts. Among these findings, we found evidence that 6 Cys34 adducts were altered between DEE-exposed and unexposed participants (i.e., 841.75, 851.76, 856.10, 860.77, 870.43, and 913.45). These adducts were biologically related to antioxidant activity.

SUBMITTER: Wong JYY

PROVIDER: S-EPMC9757949 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Exposure to diesel engine exhaust and alterations to the Cys34/Lys525 adductome of human serum albumin.

Wong Jason Y Y JYY Imani Partow P Grigoryan Hasmik H Bassig Bryan A BA Dai Yufei Y Hu Wei W Blechter Batel B Rahman Mohammad L ML Ji Bu-Tian BT Duan Huawei H Niu Yong Y Ye Meng M Jia Xiaowei X Meng Tao T Bin Ping P Downward George G Meliefste Kees K Leng Shuguang S Fu Wei W Yang Jufang J Ren Dianzhi D Xu Jun J Zhou Baosen B Hosgood H Dean HD Vermeulen Roel R Zheng Yuxin Y Silverman Debra T DT Rothman Nathaniel N Rappaport Stephen M SM Lan Qing Q

Environmental toxicology and pharmacology 20220905

We investigated whether exposure to carcinogenic diesel engine exhaust (DEE) was associated with altered adduct levels in human serum albumin (HSA) residues. Nano-liquid chromatography-high resolution mass spectrometry (nLC-HRMS) was used to measure adducts of Cys34 and Lys525 residues in plasma samples from 54 diesel engine factory workers and 55 unexposed controls. An untargeted adductomics and bioinformatics pipeline was used to find signatures of Cys34/Lys525 adductome modifications. To iden ...[more]

PMID: 36067935

Similar Datasets

Project description:BackgroundDiesel engine exhaust (DEE) exposure causes lung cancer, but the molecular mechanisms by which this occurs are not well understood.ObjectivesTo assess transcriptomic alterations in nasal epithelium of DEE-exposed factory workers to better understand the cellular and molecular effects of DEE.MethodsNasal epithelial brushings were obtained from 41 diesel engine factory workers exposed to relatively high levels of DEE (17.2-105.4 μg/m3), and 38 unexposed workers from factories without DEE exposure. mRNA was profiled for gene expression using Affymetrix microarrays. Linear modeling was used to identify differentially expressed genes associated with DEE exposure and interaction effects with current smoking status. Pathway enrichment among differentially expressed genes was assessed using EnrichR. Gene Set Enrichment Analysis (GSEA) was used to compare gene expression patterns between datasets.Results225 genes had expression associated with DEE exposure after adjusting for smoking status (FDR q < 0.25) and were enriched for genes in pathways related to oxidative stress response, cell cycle pathways such as MAPK/ERK, protein modification, and transmembrane transport. Genes up-regulated in DEE-exposed individuals were enriched among the genes most up-regulated by cigarette smoking in a previously reported bronchial airway smoking dataset. We also found that the DEE signature was enriched among the genes most altered in two previous studies of the effects of acute DEE on PBMC gene expression. An exposure-response relationship was demonstrated between air levels of elemental carbon and the first principal component of the DEE signature.ConclusionsA gene expression signature was identified for workers occupationally exposed to DEE that was altered in an exposure-dependent manner and had some overlap with the effects of smoking and the effects of acute DEE exposure. This is the first study of gene expression in nasal epithelial cells of workers heavily exposed to DEE and provides new insights into the molecular alterations that occur with DEE exposure.

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.

Dataset Information

Exposure to diesel engine exhaust and alterations to the Cys34/Lys525 adductome of human serum albumin.

Publications

Exposure to diesel engine exhaust and alterations to the Cys34/Lys525 adductome of human serum albumin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets