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儿童早期汞暴露与端粒长度和线粒体 DNA 含量的关系。

Early life exposure to mercury and relationships with telomere length and mitochondrial DNA content in European children.

机构信息

Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain; Preventive Medicine and Public Health, Food Sciences, Toxicology and Forensic Medicine Department, Universitat de València, Valencia, Spain.

Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, United Kingdom.

出版信息

Sci Total Environ. 2024 Jul 1;932:173014. doi: 10.1016/j.scitotenv.2024.173014. Epub 2024 May 9.

DOI:10.1016/j.scitotenv.2024.173014
PMID:38729362
Abstract

BACKGROUND

Telomere length (TL) and mitochondrial function expressed as mitochondrial DNA copy number (mtDNAcn) are biomarkers of aging and oxidative stress and inflammation, respectively. Methylmercury (MeHg), a common pollutant in fish, induces oxidative stress. We hypothesized that elevated oxidative stress from exposure to MeHg decreases mtDNAcn and shortens TL.

METHODS

Study participants are 6-11-year-old children from the HELIX multi-center birth cohort study, comprising six European countries. Prenatal and postnatal total mercury (THg) concentrations were measured in blood samples, TL and mtDNAcn were determined in child DNA. Covariates and confounders were obtained by questionnaires. Robust regression models were run, considering sociodemographic and lifestyle covariates, as well as fish consumption. Sex, ethnicity, and fish consumption interaction models were also run.

RESULTS

We found longer TL with higher pre- and postnatal THg blood concentrations, even at low-level THg exposure according to the RfD proposed by the US EPA. The prenatal association showed a significant linear relationship with a 3.46 % increase in TL for each unit increased THg. The postnatal association followed an inverted U-shaped marginal non-linear relationship with 1.38 % an increase in TL for each unit increased THg until reaching a cut-point at 0.96 μg/L blood THg, from which TL attrition was observed. Higher pre- and postnatal blood THg concentrations were consistently related to longer TL among cohorts and no modification effect of fish consumption nor children's sex was observed. No association between THg exposure and mtDNAcn was found.

DISCUSSION

We found evidence that THg is associated with TL but the associations seem to be time- and concentration-dependent. Further studies are needed to clarify the mechanism behind the telomere changes of THg and related health effects.

摘要

背景

端粒长度(TL)和线粒体功能分别以线粒体 DNA 拷贝数(mtDNAcn)表示,是衰老和氧化应激、炎症的生物标志物。甲基汞(MeHg)是鱼类中的一种常见污染物,会引起氧化应激。我们假设,暴露于 MeHg 引起的氧化应激增加会降低 mtDNAcn 并缩短 TL。

方法

研究参与者是来自 HELIX 多中心出生队列研究的 6-11 岁儿童,该研究包括六个欧洲国家。在血液样本中测量了产前和产后总汞(THg)浓度,在儿童 DNA 中测定了 TL 和 mtDNAcn。通过问卷获得了协变量和混杂因素。运行了稳健回归模型,考虑了社会人口统计学和生活方式协变量以及鱼类摄入量。还运行了性别、种族和鱼类摄入量的交互模型。

结果

我们发现,即使在根据美国环保署提出的 RfD 处于低水平 THg 暴露的情况下,较高的产前和产后 THg 血浓度也与较长的 TL 相关。产前关联呈线性关系,每单位 THg 增加 3.46%,TL 增加。产后关联呈倒 U 型边际非线性关系,THg 每单位增加 1.38%,TL 增加,直到达到血 THg 0.96μg/L 的切点,从那时起,TL 就会缩短。较高的产前和产后血 THg 浓度与各队列中较长的 TL 一直相关,并且没有观察到鱼类摄入量或儿童性别对 TL 的修饰作用。THg 暴露与 mtDNAcn 之间没有关联。

讨论

我们发现 THg 与 TL 之间存在关联,但这些关联似乎与时间和浓度有关。需要进一步的研究来阐明 THg 对端粒变化的作用机制及其相关的健康影响。

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