@article {286, title = {Haloacetonitriles Induce Structure-Related Cellular Toxicity Through Distinct Proteome Thiol Reaction Mechanisms.}, journal = {ACS Environ Au}, volume = {5}, year = {2025}, month = {2025 Jan 15}, pages = {101-113}, abstract = {

Haloacetonitriles (HANs) are a class of toxic drinking water disinfection byproducts (DBPs). However, the toxicity mechanisms of HANs remain unclear. We herein investigated the structure-related in vitro toxicity of 6 representative HANs by utilizing complementary bioanalytical approaches. Dibromoacetonitrile (DBAN) displayed strong cytotoxicity and Nrf2 oxidative stress responses, followed by monohalogenated HANs (monoHANs) while other polyhalogenated HANs (polyHANs) exhibited little toxicity. Activity based protein profiling (ABPP) revealed that toxic HANs adduct to human proteome thiols, supporting thiol reactivity as the primary toxicity mechanism for HANs. By using glutathione (GSH) as a thiol surrogate, monoHANs reacted with GSH via S2 while polyHANs reacted through ultrafast addition reactions. In contrast, DBAN generated an unexpected fully debrominated product and glutathione disulfide (GSSG). The unique reaction of DBAN with GSH was found to be mediated by radicals which was supported by electron paramagnetic resonance (EPR) spectroscopy and by radical trapping reagent reaction quenching. Shotgun proteomics further revealed that monoHANs and DBAN adducted to proteome thiols in live cells forming dehalogenated adducts. Multiple antioxidant proteins, SOD1, CSTB, and GAPDH, were adducted by toxic HANs at specific cysteine residues. This study highlights the structurally selective toxicity of HANs in human cells, which are attributed to their distinct reactions with proteome thiols.

}, issn = {2694-2518}, doi = {10.1021/acsenvironau.4c00068}, author = {Yeung, Kirsten and Xie, Linna and Nair, Pranav and Peng, Hui} } @article {293, title = {A Rapid Testing Kit for 6PPD Screening in Rubber Products.}, journal = {Anal Chem}, year = {2025}, month = {2025 Apr 26}, abstract = {

-(1,3-dimethylbutyl)--phenyl--phenylenediamine (6PPD) has received increasing attention due to its ubiquitous environmental occurrence and extreme aquatic toxicity of its oxidation product 6PPD-quinone. Given 6PPD{\textquoteright}s application as an antioxidant in a wide array of rubber products, cost-effective detection of 6PPD is important for product and waste management. We herein developed a rapid testing kit for the detection (\<10 min) of 6PPD in rubber products with low costs (\<$1/sample), which was inspired by the observation of a red-colored product after 6PPD exposure to oxidants. The selectivity of this reaction was evaluated by 14 structurally diverse phenols and anilines. Interestingly, the protonated -1,3-dimethyl butyl--phenyl quinone diimine (6QDI+H), rather than its neutral or radical counterparts, appeared to be the red-colored product with λ = 490 nm. We further developed a "green" and user-friendly 6PPD rapid testing kit, which was further applied to a wide array of 50 rubber products. 6PPD was detected in 22 out of 50 samples, with a strong agreement ( = 0.896) observed between the results of the rapid testing kit and LC-MS. In summary, this study introduces a 6PPD rapid testing kit for users without requiring expertise in chemistry.

}, issn = {1520-6882}, doi = {10.1021/acs.analchem.5c00079}, author = {Li, Zhuoyuan and Xie, Linna and Nair, Pranav and Yeung, Kirsten and Meek, Oliver and Tao, Juan and Hiki, Kyoshiro and Hao, Chunyan and Peng, Hui} } @article {222, title = {Dynamic Wood Smoke Aerosol Toxicity during Oxidative Atmospheric Aging.}, journal = {Environ Sci Technol}, year = {2023}, month = {2023 Jan 11}, abstract = {

Wildfires are a major source of biomass burning aerosol to the atmosphere, with their incidence and intensity expected to increase in a warmer future climate. However, the toxicity evolution of biomass burning organic aerosol (BBOA) during atmospheric aging remains poorly understood. In this study, we report a unique set of chemical and toxicological metrics of BBOA from pine wood smoldering during multiphase aging by gas-phase hydroxyl radicals (OH). Both the fresh and OH-aged BBOA show activity relevant to adverse health outcomes. The results from two acellular assays (DTT and DCFH) show significant oxidative potential (OP) and reactive oxygen species (ROS) formation in OH-aged BBOA. Also, radical concentrations in the aerosol assessed by electron paramagnetic resonance (EPR) spectroscopy increased by 50\% following heterogeneous aging. This enhancement was accompanied by a transition from predominantly carbon-centered radicals (85\%) in the fresh aerosol to predominantly oxygen-centered radicals (76\%) following aging. Both the fresh and aged biomass burning aerosols trigger prominent antioxidant defense during the exposure, indicating the induction of oxidative stress by BBOA in the atmosphere. By connecting chemical composition and toxicity using an integrated approach, we show that short-term aging initiated by OH radicals can produce biomass burning particles with a higher particle-bound ROS generation capacity, which are therefore a more relevant exposure hazard for residents in large population centers close to wildfire regions than previously studied fresh biomass burning emissions.

}, issn = {1520-5851}, doi = {10.1021/acs.est.2c05929}, author = {Wang, Shunyao and Gallimore, Peter J and Liu-Kang, Carolyn and Yeung, Kirsten and Campbell, Steven J and Utinger, Battist and Liu, Tengyu and Peng, Hui and Kalberer, Markus and Chan, Arthur W H and Abbatt, Jonathan P D} } @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 = {

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.

}, 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} }