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中国孕妇尿液中多环芳烃代谢物:浓度、变异性、影响因素及与氧化应激生物标志物的关系。

Urinary polycyclic aromatic hydrocarbon metabolites in Chinese pregnant women: Concentrations, variability, predictors, and association with oxidative stress biomarkers.

机构信息

State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan 430030, Hubei, China.

Center for Public Health Laboratory Service, Institute of Environmental Health, Wuhan Centers for Disease Control & Prevention, Wuhan, Hubei 430024, PR China.

出版信息

Sci Total Environ. 2024 Nov 10;950:175121. doi: 10.1016/j.scitotenv.2024.175121. Epub 2024 Jul 30.

DOI:10.1016/j.scitotenv.2024.175121
PMID:39084365
Abstract

Polycyclic aromatic hydrocarbons (PAHs) are a class of pervasive contaminants having adverse health effects. Urinary monohydroxylated PAHs (OH-PAHs) are commonly employed as biomarkers to estimate PAH exposure levels in humans. However, little is understood about the variability in OH-PAHs among pregnant women across trimesters and their relationship with oxidative stress biomarkers (OSBs). Based on a prospective birth cohort study conducted in Wuhan, China, we selected 644 women who donated (spot) urine samples across different trimesters and measured the urinary concentrations of eight OH-PAHs and three selected OSBs (8-OHG, 8-OHdG, and HNEMA) to explore the relationship between the OH-PAHs and OSBs. Pregnant women were found to be ubiquitously exposed to the PAHs, with detection rates of the OH-PAHs ranging from 86.3% to 100%. 2-Hydroxynaphthalene (2-OH-Nap) had the highest urinary concentrations among the OH-PAHs during the three trimesters (specific gravity-adjusted median values for the first, second, and third trimesters: 1.86, 2.39, and 2.20 ng/mL, respectively). However, low reproducibility of the OH-PAHs was observed across the three trimesters with intraclass correlation coefficients ranged between 0.02 and 0.22. Most urinary OH-PAHs had the highest concentrations at the first trimester and the lowest at the third trimester. Some OH-PAH concentrations were higher in pregnant women with lower educational level [2-hydroxyphenanthrene (2-OH-Phen) and 3-hydroxyphenanthrene (3-OH-Phen)], those who were overweight [2-OH-Nap, 2/3-hydroxyfluorene (2/3-OH-Fluo), 2-OH-Phen, and 4-hydroxyphenanthrene (4-OH-Phen)], those who were unemployed during pregnancy [1-hydroxynaphthalene, 1/9-hydroxyphenanthrene, and 4-OH-Phen], and the samples donated in summer (most OH-PAHs, except for 2-OH-Nap). In multivariable linear mixed-effects model analyses, every OH-PAH was found to be significantly associated with increased levels of the three OSBs. For example, each interquartile range-fold increase in 2/3-OH-Fluo concentration was associated with the largest increase in 8-OHdG (65.4%) and 8-OHG (49.1%), while each interquartile range-fold increase in 3-OH-Phen concentration was associated with the largest increase in HNEMA (76.3%). Weighted quantile sum regression models, which were used to examine the joint effect of OH-PAH mixture on the OSBs, revealed positive associations between the OH-PAH mixture exposure and the OSBs. Specifically, 2/3-OH-Fluo and 2-OH-Nap were the major contributors in the association with oxidative damage of nucleic acids (8-OHdG and 8-OHG), while hydroxyphenanthrenes and 1-hydroxypyrene were the major contributors in the association with oxidative damage of lipid (HNEMA). Further work is required to examine the potential mediating role of oxidative stress in the relationship of adverse health outcomes with elevated PAH exposure among pregnant women.

摘要

多环芳烃(PAHs)是一类普遍存在的污染物,具有不良的健康影响。尿中单羟基化多环芳烃(OH-PAHs)通常被用作估计人类 PAH 暴露水平的生物标志物。然而,人们对孕妇在不同孕期的 OH-PAHs 变异及其与氧化应激生物标志物(OSBs)的关系知之甚少。基于在中国武汉进行的一项前瞻性出生队列研究,我们选择了 644 名在不同孕期捐献(点)尿样的孕妇,并测量了 8 种 OH-PAHs 和 3 种选定的 OSBs(8-OHG、8-OHdG 和 HNEMA)的尿浓度,以探讨 OH-PAHs 与 OSBs 之间的关系。研究发现孕妇普遍接触 PAHs,OH-PAHs 的检出率为 86.3%至 100%。在三个孕期中,2-羟萘(2-OH-Nap)的尿浓度最高(第一、第二和第三个孕期比重调整后的中位数分别为 1.86、2.39 和 2.20ng/mL)。然而,OH-PAHs 在三个孕期的重现性较差,组内相关系数在 0.02 到 0.22 之间。大多数尿 OH-PAHs 在第一个孕期的浓度最高,在第三个孕期的浓度最低。一些 OH-PAHs 的浓度在教育程度较低的孕妇中较高(2-羟菲和 3-羟菲)、超重的孕妇中较高(2-OH-Nap、2/3-羟芴、2-OH-Phen 和 4-羟菲)、孕期失业的孕妇中较高(1-萘酚、1/9-羟菲和 4-羟菲)和夏季捐献的样本中较高(除 2-OH-Nap 外的大多数 OH-PAHs)。在多变量线性混合效应模型分析中,每个 OH-PAH 都与三种 OSBs 水平的升高显著相关。例如,2/3-OH-Fluo 浓度每增加一个四分位间距倍数,与 8-OHdG(65.4%)和 8-OHG(49.1%)的最大增加相关,而 3-OH-Phen 浓度每增加一个四分位间距倍数,与 HNEMA(76.3%)的最大增加相关。加权分位数总和回归模型用于研究 OH-PAH 混合物对 OSBs 的联合效应,结果表明 OH-PAH 混合物暴露与 OSBs 之间存在正相关。具体来说,2/3-OH-Fluo 和 2-OH-Nap 是与核酸氧化损伤(8-OHdG 和 8-OHG)相关的主要贡献者,而羟基菲和 1-羟基芘是与脂质氧化损伤(HNEMA)相关的主要贡献者。需要进一步研究以检验氧化应激在孕妇 PAH 暴露升高与不良健康后果之间的关系中的潜在中介作用。

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