Decreased DNA repair capacity caused by exposure to metal mixtures is modulated by the PARP1 rs1136410 variant in newborns from a polluted metropolitan area

被引:1
|
作者
Paz-Sabillon, Marvin [1 ]
Montes-Castro, Nereida [2 ]
Torres-Sanchez, Luisa [3 ]
Del Razo, Luz M. [1 ]
Cordova, Emilio J. [4 ]
Quintanilla-Vega, Betzabet [1 ]
机构
[1] Cinvestav, Dept Toxicol, Ave IPN 2508, Mexico City 07360, Mexico
[2] Autonomous Univ West, Dept Hlth Sci, Culiacan Reg Unit, Lola Beltran Blvd, Culiacan 80020, Sinaloa, Mexico
[3] Natl Inst Publ Hlth, Ctr Populat Hlth Res, Ave Univ 655, Cuernavaca 62100, Morelos, Mexico
[4] Natl Inst Genom Med, Dept Clin Res, Oncogen Consortium Lab, Mexico City 14610, Mexico
关键词
Newborns; Prenatal exposure; Metal mixture; DNA repair; PARP1; variant; BIOMONITORING EQUIVALENTS; VAL762ALA POLYMORPHISM; PRENATAL EXPOSURE; BLOOD; PARP1; LEAD; SELENIUM; CANCER; DAMAGE; ONSET;
D O I
10.1016/j.envres.2023.117631
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Background: 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. Aim: 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. Methods: 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. Results: 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). Conclusion: Prenatal exposure to metal mixtures negatively affected DRC in newborns, and the PARP1 rs1136410 variant had a modulating role in this association.
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页数:10
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  • [1] Prenatal exposure to mixtures of potentially toxic and essential metals decreased DNA repair capacity in newborns from a polluted area
    Paz-Sabillon, M.
    Montes-Castro, N.
    Del Razo, L. M.
    Torres-Sanchez, L.
    Quintanilla-Vega, B.
    TOXICOLOGY LETTERS, 2023, 384 : S222 - S222