@article {140,
	title = {Proteome-wide effects of naphthalene-derived secondary organic aerosol in BEAS-2B cells are caused by short-lived unsaturated carbonyls.},
	journal = {Proc Natl Acad Sci U S A},
	year = {2020},
	month = {2020 Sep 28},
	abstract = {<p>Exposure to air pollution causes adverse health outcomes, but the toxicity mechanisms remain unclear. Here, we investigated the dynamic toxicities of naphthalene-derived secondary organic aerosol (NSOA) in a human bronchial epithelial cell line (BEAS-2B) and identified the chemical components responsible for toxicities. The chemical composition of NSOA was found to vary with six simulated atmospheric aging conditions (C-C), as characterized by high-resolution mass spectrometry and ion mobility mass spectrometry. Global proteome profiling reveals dynamic evolution in toxicity: Stronger proteome-wide impacts were detected in fresh NSOA, but the effects declined along with atmospheric aging. While Nrf2-regulated proteins (e.g., ) were significantly up-regulated, the majority (78 to 97\%) of proteins from inflammation and other pathways were down-regulated by NSOA exposure (e.g., ). This pattern is distinct from the reactive oxygen species (ROS)-mediated toxicity pathway, and an alternative cysteine reaction pathway was revealed by the decreased abundance of proteins (e.g., ) prone to posttranslational thiol modification. This pathway was further validated by observing decreased Nrf2 response in reporter cells, after preincubating NSOA with cysteine. Ethynyl-naphthalene probe was employed to confirm the alkylation of cellular proteome thiols on the proteome-wide level by fresh NSOA via in-gel fluorescence imaging. Nontarget analysis identified several unsaturated carbonyls, including naphthoquinones and hydroxylated naphthoquinones, as the toxic components responsible for cysteine reactivity. Our study provides insights into the dynamic toxicities of NSOA during atmospheric aging and identifies short-lived unsaturated carbonyls as the predominant toxic components at the posttranslational level.</p>},
	issn = {1091-6490},
	doi = {10.1073/pnas.2001378117},
	author = {Han, Jiajun and Wang, Shunyao and Yeung, Kirsten and Yang, Diwen and Gu, Wen and Ma, Zhiyuan and Sun, Jianxian and Wang, Xiaomin and Chow, Chung-Wai and Chan, Arthur W H and Peng, Hui}
}
@article {130,
	title = {Toxicokinetics of Brominated Azo Dyes in the Early Life Stages of Zebrafish () Is Prone to Aromatic Substituent Changes.},
	journal = {Environ Sci Technol},
	volume = {54},
	year = {2020},
	month = {2020 04 07},
	pages = {4421-4431},
	abstract = {<p>Brominated azo dyes (BADs) have been identified as predominant indoor brominated pollutants in daycare dust; thus, their potential health risk to children is of concern. However, the toxicities of BADs remain elusive. In this study, the toxicokinetics of two predominant BADs, Disperse Blue 373 (DB373) and Disperse Violet 93 (DV93), and their suspect metabolite 2-bromo-4,6-dinitroaniline (BDNA) was investigated in embryos of zebrafish (). The bioconcentration factor of DV93 at 120 hpf is 6.2-fold lower than that of DB373. The nontarget analysis revealed distinct metabolism routes between DB373 and DV93 by reducing nitro groups to nitroso (DB373) or amine (DV93), despite their similar structures. NAD(P)H quinone oxidoreductase 1 (NQO1) and pyruvate dehydrogenase were predicted as the enzymes responsible for the reduction of DB373 and DV93 by correlating time courses of the metabolites and enzyme development. Further in vitro recombinant enzyme and in vivo inhibition results validated NQO1 as the enzyme specifically reducing DB373, but not DV93. Global proteome profiling revealed that the expression levels of proteins from the "apoptosis-induced DNA fragmentation" pathway were significantly upregulated by all three BADs, supporting the bioactivation of BADs to mutagenic aromatic amines. This study discovered the bioactivation of BADs via distinct eukaryotic enzymes, implying their potential health risks.</p>},
	keywords = {Animals, Azo Compounds, Child, Dust, Embryo, Nonmammalian, Humans, Mutagens, Toxicokinetics, Zebrafish},
	issn = {1520-5851},
	doi = {10.1021/acs.est.9b07178},
	author = {Han, Jiajun and Yang, Diwen and Hall, David Ross and Liu, Jiabao and Sun, Jianxian and Gu, Wen and Tang, Song and Alharbi, Hattan A and Jones, Paul D and Krause, Henry M and Peng, Hui}
}
