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接触挥发性有机化合物可能与氧化 DNA 损伤介导的儿童哮喘有关。

Exposure to volatile organic compounds may be associated with oxidative DNA damage-mediated childhood asthma.

机构信息

Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, School of Life Sciences, South China Normal University, Guangzhou 510631, China; Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School o f Life Sciences, South China Normal University, Guangzhou 510631, China.

Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, School of Life Sciences, South China Normal University, Guangzhou 510631, China.

出版信息

Ecotoxicol Environ Saf. 2021 Mar 1;210:111864. doi: 10.1016/j.ecoenv.2020.111864. Epub 2021 Jan 4.

Abstract

Volatile organic compounds (VOCs) are important and ubiquitous air pollutants, which may lead to a significant increase in the prevalence of respiratory diseases. To investigate the relationships between VOCs exposure and childhood asthma, 252 asthmatic children and 69 healthy children were recruited. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG, a biomarker of oxidative DNA damage), trans-3'-hydroxycotinine (OH-Cot, a biomarker of passive smoking) and 27 VOC metabolites were simultaneously determined by an ultra-high-performance liquid chromatography-tandem mass spectrometer. Results showed that levels of 8-OHdG and most VOC metabolites in asthmatic children were significantly higher than those in healthy children. More than half of the VOC metabolites were significantly and positively associated with OH-Cot with maximal β coefficient of 0.169, suggesting that second-hand smoking is one important source of VOCs exposure for children in Guangzhou. Significant dose-response relationships between most VOC metabolites and 8-OHdG were observed. Each unit increase in ln-transformed VOC metabolite levels was significantly associated with 5.5-32% increase in ln-transformed 8-OHdG level. Moreover, each unit increase in ln-transformed 8-OHdG level was associated with an 896% increased odd ratios (OR) of asthma in children (OR = 9.96, 95% confidence intervals (CI): 4.75, 20.9), indicating that oxidative stress induced by VOCs exposure may have a significant impact on childhood asthma. Urinary 3-&4-Methylhippuric acid (3-&4-MHA, OR: 5.78, 95% CI: 3.50, 9.54), rac 2-Aminothiazoline-4-carboxylic acid (ATCA, OR: 2.90, 95% CI: 1.69, 4.99) and N-Acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA, OR: 2.76, 95% CI: 1.73, 4.43) which may derive from m/p-xylene, cyanide and 1,3-butadiene exposure, respectively, could significantly and maximally increase the odds of asthma. Interestingly, they also had the strongest associations with 8-OHdG among all investigated VOC metabolites. Moreover, DHBMA strongly correlated with most VOC metabolites. Hence, DHBMA is a suitable biomarker to indicate not only VOCs exposure profile, but also the DNA damage-mediated asthma induced by VOCs.

摘要

挥发性有机化合物(VOCs)是重要且普遍存在的空气污染物,可能会导致呼吸道疾病的患病率显著增加。为了研究 VOCs 暴露与儿童哮喘之间的关系,招募了 252 名哮喘儿童和 69 名健康儿童。通过超高效液相色谱-串联质谱法同时测定了尿液中的 8-羟基-2'-脱氧鸟苷(8-OHdG,氧化 DNA 损伤的生物标志物)、反式-3'-羟基可替宁(OH-Cot,被动吸烟的生物标志物)和 27 种 VOC 代谢物。结果表明,哮喘儿童的 8-OHdG 和大多数 VOC 代谢物水平明显高于健康儿童。超过一半的 VOC 代谢物与 OH-Cot 呈显著正相关,最大 β 系数为 0.169,表明二手烟是广州儿童 VOCs 暴露的重要来源之一。大多数 VOC 代谢物与 8-OHdG 之间存在显著的剂量-反应关系。ln 转化的 VOC 代谢物水平每增加一个单位,ln 转化的 8-OHdG 水平就会显著增加 5.5-32%。此外,ln 转化的 8-OHdG 水平每增加一个单位,儿童哮喘的比值比(OR)就会增加 896%(OR=9.96,95%置信区间(CI):4.75,20.9),表明 VOCs 暴露引起的氧化应激可能对儿童哮喘有显著影响。尿中 3-和 4-甲基马尿酸(3-和 4-MHA,OR:5.78,95%CI:3.50,9.54)、rac 2-氨基噻唑啉-4-羧酸(ATCA,OR:2.90,95%CI:1.69,4.99)和 N-乙酰-S-(3,4-二羟基丁基)-L-半胱氨酸(DHBMA,OR:2.76,95%CI:1.73,4.43)可能分别来自间/对二甲苯、氰化物和 1,3-丁二烯暴露,可显著增加哮喘的几率。有趣的是,它们与所有研究的 VOC 代谢物中的 8-OHdG 之间也具有最强的关联。此外,DHBMA 与大多数 VOC 代谢物强烈相关。因此,DHBMA 是一种合适的生物标志物,不仅可以指示 VOCs 暴露情况,还可以指示 VOCs 引起的 DNA 损伤介导的哮喘。

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