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

Jason Y.Y. Wong, Partow Imani, Hasmik Grigoryan, Bryan A. Bassig, Yufei Dai, Wei Hu, Batel Blechter, Mohammad L. Rahman, Bu Tian Ji, Huawei Duan, Yong Niu, Meng Ye, Xiaowei Jia, Tao Meng, Ping Bin, George Downward, Kees Meliefste, Shuguang Leng, Wei Fu, Jufang YangDianzhi Ren, Jun Xu, Baosen Zhou, H. Dean Hosgood, Roel Vermeulen, Yuxin Zheng, Debra T. Silverman, Nathaniel Rothman, Stephen M. Rappaport, Qing Lan

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number103966
JournalEnvironmental Toxicology and Pharmacology
Volume95
DOIs
StatePublished - Oct 2022

Keywords

  • Adductomics
  • Biomarkers
  • Cys34 adductome
  • Diesel engine exhaust
  • Environmental epidemiology
  • Machine learning

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

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