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

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.

Prenatal Exposure to Potentially Toxic Metals and Their Effects on Genetic Material in Offspring: a Systematic Review.

In recent years, the background level of environmental pollutants, including metals, has increased. Pollutant exposure during the earliest stages of life may determine chronic disease susceptibility in adulthood because of genetic or epigenetic changes. The objective of this review was to identify the association between prenatal and early postnatal exposure to potentially toxic metals (PTMs) and their adverse effects on the genetic material of offspring. A systematic review was carried out following the Cochrane methodology in four databases: PubMed, Scopus, Web of Science, and the Cochrane Library. Eligible papers were those conducted in humans and published in English between 2010/01/01 and 2021/04/30. A total of 57 articles were included, most of which evaluated prenatal exposure. Most commonly evaluated PTMs were As, Cd, and Pb. Main adverse effects on the genetic material of newborns associated with PTM prenatal exposure were alterations in telomere length, gene or protein expression, mitochondrial DNA content, metabolomics, DNA damage, and epigenetic modifications. Many of these effects were sex-specific, being predominant in boys. One article reported a synergistic interaction between As and Hg, and two articles observed antagonistic interactions between PTMs and essential metals, such as Cu, Se, and Zn. The findings in this review highlight that the problem of PTM exposure persists, affecting the most susceptible populations, such as newborns. Some of these associations were observed at low concentrations of PTMs. Most of the studies have focused on single exposures; however, three interactions between essential and nonessential metals were observed, highlighting that metal mixtures need more attention.