Department of Toxicology, Cinvestav, Ave. IPN 2508, San Pedro Zacatenco, Mexico City, 07360, Mexico.
Department of Health Sciences, Autonomous University of the West, Culiacán Regional Unit, Lola Beltrán Blvd, Culiacán, Sinaloa, 80020, Mexico.
Environ Res. 2024 Jan 15;241:117631. doi: 10.1016/j.envres.2023.117631. Epub 2023 Nov 14.
DNA damage caused by exposure to metal mixtures and the potential modulating role of genes involved in DNA repair and the antioxidant response have not been evaluated in newborns.
The aim was to evaluate the association between prenatal exposure to metal mixtures and DNA repair capacity (DRC) in newborns from the Metropolitan Area of Mexico City (MAMC), a heavily polluted area, and the impact of variants in genes involved in DNA repair and the antioxidant response on this association.
We analyzed cord blood samples obtained at delivery from 125 healthy newborns from the MAMC. Twenty-four elements were determined by inductively coupled plasma mass spectrometry (ICP‒MS), but only 12 (Cu, I, Se, Zn, As, Ba, Cs, Mn, Sb, Sr, Pb, and Ti) were quantified in most samples. DRC was assessed by the challenge-comet assay, and OGG1, PARP1, and NFE2L2 genotyping was performed with TaqMan probes. Metal mixtures were identified and analyzed using principal component analysis (PCA) and weighted quantile sum (WQS) regression. Independent adjusted linear regression models were used to evaluate the associations.
A null DRC was observed in 46% of newborns. The metals with the highest concentrations were Mn, Sr, Ti, and Pb. Essential elements showed normal levels. Only the mixture characterized by increased As, Cs, Cu, Se, and Zn levels was inversely associated with DRC. As was the principal contributor (37.8%) in the negative direction in the DRC followed by Ba and Sb, according to the WQS regression. Newborns carrying of the derived (G) allele of the PARP1 rs1136410 variant showed decreased DRC by exposure to some potentially toxic metals (PTMs) (As, Cs, and Ba).
Prenatal exposure to metal mixtures negatively affected DRC in newborns, and the PARP1 rs1136410 variant had a modulating role in this association.
暴露于金属混合物会造成 DNA 损伤，而涉及 DNA 修复和抗氧化反应的基因的潜在调节作用在新生儿中尚未得到评估。
本研究旨在评估墨西哥城大都市区（MAMC）内新生儿产前暴露于金属混合物与 DNA 修复能力（DRC）之间的关联，并探讨涉及 DNA 修复和抗氧化反应的基因变异对此关联的影响。
我们分析了来自 MAMC 的 125 名健康新生儿的脐带血样本。通过电感耦合等离子体质谱法（ICP-MS）测定了 24 种元素，但大多数样本仅定量了其中的 12 种（Cu、I、Se、Zn、As、Ba、Cs、Mn、Sb、Sr、Pb 和 Ti）。通过彗星试验评估 DRC，使用 TaqMan 探针进行 OGG1、PARP1 和 NFE2L2 基因分型。采用主成分分析（PCA）和加权分位数总和（WQS）回归识别和分析金属混合物。采用独立调整的线性回归模型评估相关性。
46%的新生儿出现了 DRC 缺失。浓度最高的金属为 Mn、Sr、Ti 和 Pb。必需元素处于正常水平。只有表现为 As、Cs、Cu、Se 和 Zn 水平升高的混合物与 DRC 呈负相关。根据 WQS 回归，As 是 DRC 呈负向的主要贡献者（占 37.8%），其次是 Ba 和 Sb。PARP1 rs1136410 变体的衍生（G）等位基因携带者在暴露于一些潜在有毒金属（PTMs）（As、Cs 和 Ba）时，DRC 降低。
产前暴露于金属混合物会对新生儿的 DRC 产生负面影响，而 PARP1 rs1136410 变体在这种关联中具有调节作用。
