Heterogeneous Oxidation Products of Fine Particulate Isoprene Epoxydiol-Derived Methyltetrol Sulfates Increase Oxidative Stress and Inflammatory Gene Responses in Human Lung Cells
Heterogeneous Oxidation Products of Fine Particulate Isoprene Epoxydiol-Derived Methyltetrol Sulfates Increase Oxidative Stress and Inflammatory Gene Responses in Human Lung Cells
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DOI：
10.1021/acs.chemrestox.3c00278
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发表时间：
2023-10-31
影响因子：
4.1
通讯作者：
Surratt，Jason D.
中科院分区：
文献类型：
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作者：
Khan，Faria;Chen，Yuzhi;Surratt，Jason D.
异戊二烯是大气中含量最多的非甲烷碳氢化合物，羟基自由基（·OH）引发的氧化是造成环境细颗粒物中大量二次有机气溶胶（SOA）的原因。细颗粒硫酸2-甲基四醇非对映异构体（2-MTSs）是由异戊二烯衍生的环氧二醇与无机硫酸盐气溶胶在低一氧化氮条件下经酸催化多相化学反应生成的丰富的SOA产物。我们最近证明，颗粒状2- mts的非均相·OH氧化导致多功能有机硫酸盐（OSs）的颗粒相形成。然而，尚不确定大气化学老化颗粒2- mts是否会在人肺细胞内引起毒性作用。我们发现，暴露于细颗粒2- mts中，抑制浓度-50 （IC50）值下降，这些细颗粒2- mts被·OH异质性老化0至22天，表明颗粒毒性增加了BEAS-2B肺细胞。肺细胞进一步表现出氧化应激和炎症相关基因表达的浓度依赖性调节。对化学混合物进行了主成分分析，发现暴露于老化多功能OSs与目标基因表达改变之间存在正相关。单独暴露于颗粒2- mts与抗活性氧（ROS）相关基因（NQO-1、SOD-2和cat）的表达改变有关，这表明细胞对ROS有反应。·OH暴露增加颗粒2- mts的衰老与谷胱甘肽途径相关基因（GCLMandGCLC）和抗炎基因（IL-10）的表达增加有关。
Hydroxyl radical (·OH)-initiated oxidation of isoprene, the most abundant nonmethane hydrocarbon in the atmosphere, is responsible for substantial amounts of secondary organic aerosol (SOA) within ambient fine particles. Fine particulate 2-methyltetrol sulfate diastereoisomers (2-MTSs) are abundant SOA products formed via acid-catalyzed multiphase chemistry of isoprene-derived epoxydiols with inorganic sulfate aerosols under low-nitric oxide conditions. We recently demonstrated that heterogeneous·OH oxidation of particulate 2-MTSs leads to the particle-phase formation of multifunctional organosulfates (OSs). However, it remains uncertain if atmospheric chemical aging of particulate 2-MTSs induces toxic effects within human lung cells. We show that inhibitory concentration-50 (IC50) values decreased from exposure to fine particulate 2-MTSs that were heterogeneously aged for 0 to 22 days by·OH, indicating increased particulate toxicity in BEAS-2B lung cells. Lung cells further exhibited concentration-dependent modulation of oxidative stress- and inflammatory-related gene expression. Principal component analysis was carried out on the chemical mixtures and revealed positive correlations between exposure to aged multifunctional OSs and altered expression of targeted genes. Exposure to particulate 2-MTSs alone was associated with an altered expression of antireactive oxygen species (ROS)-related genes (NQO-1, SOD-2,andCAT) indicative of a response to ROS in the cells. Increased aging of particulate 2-MTSs by·OH exposure was associated with an increased expression of glutathione pathway-related genes (GCLMandGCLC) and an anti-inflammatory gene (IL-10).