Cortex and hippocampus DNA epigenetic response to a long-term arsenic exposure via drinking water

Du, Xiaodong; Tian, Meiping; Wang, Xiaoxue; Zhang, Jie; Huang, Qingyu; Liu, Liangpo; Shen, Heqing

doi:10.1016/j.envpol.2017.11.083

Cited by 49 publications

(25 citation statements)

References 67 publications

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“…Tellez-Plaza et al found that increased 5hmC levels in blood DNA were associated with cadmium and arsenic exposure in adult participants that aged 45 to 74 years old in the Strong Heart Study [42]. However, decreases in 5hmC have been reported in both the brain tissues of rats and HEK293T cells treated with arsenite [19,43]. A study based on a U.S. pre-birth cohort reported that maternal mercury exposure is associated with lower 5hmC levels in cord blood and this association could be persistent in early childhood [44].…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism through which PAH exposure causes DNA hydroxymethylation alteration is unclear. Evidence from both in vitro and in vivo studies suggests that OS may play a role in the change in global levels of 5hmC% [19,20,51]. Interestingly, the leading hypothesized mechanisms for PAHassociated toxicity include the generation of ROS that lead to OS [52].…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism of DNA demethylation in pathological process remains obscure. A study revealed that OS may lead to a reduction of 5hmC in arsenic-induced neurotoxicity [19]. A global decrease of 5hmC was found in mice depleted for the major antioxidant enzymes GPx1 and 2 [20], which indicated the role ROS may play in the 5hmC dysregulation.…”

Section: Introductionmentioning

confidence: 99%

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Decreased global DNA hydroxymethylation in neural tube defects: Association with polycyclic aromatic hydrocarbons

et al. 2019

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5-Hydroxymethylcytosine (5hmC), a distinct epigenetic marker that plays a role in DNA active demethylation, has been reported to be important for embryonic development and may respond to environmental exposure. No studies have evaluated the association between DNA hydroxymethylation and the risk for fetal neural tube defects (NTDs), with consideration of prenatal exposure to polycyclic aromatic hydrocarbons (PAHs), a risk factor for NTDs. We measured the global levels of 5hmC% in neural tissue from 92 terminated NTD cases and 33 terminated non-malformed fetuses. A lower level of 5hmC% was found in the NTD cases (median [interquartile range]: 0.25 [0.12-0.39]) compared to the controls (0.45 [0.19-1.00]). After adjusting for periconceptional folate supplementation, risk for NTDs increased with decreasing tertiles of 5hmC% (odds ratio: 7.89, 95% confidence interval: 2.32, 26.86, for the lowest tertile relative to the top tertile; p for trend = 0.002). Linear regression revealed that concentrations of highmolecular-weight PAHs (H_PAHs) in fetal liver tissue were negatively associated with log2transformed 5hmC%. Superoxide dismutase activity and 5hmC% were positively correlated in fetal neural tissue (r s = 0.64; p < 0.05). A mouse whole-embryo culture model was used for further validation. Decreased levels of 5hmC% and increased levels of reactive oxygen species were found in mouse embryos treated with BaP, a well-studied PAH. Taken together, levels of 5hmC% in fetal neural tissue were inversely associated with the risk for NTDs, and this association may be related to oxidative stress induced by exposure to PAHs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Decreased global DNA hydroxymethylation in neural tube defects: Association with polycyclic aromatic hydrocarbons

et al. 2019

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“…Arsenite (iAs III) and trivalent organic (methylated) arsenicals react with thiols (-SH) in proteins and inhibit their activity. Other mechanisms include epigenetic alteration, oxidative stress, inflammation, and autophagic defects [24][25][26]. ROS • , which gives rise to other forms of ROS [29].…”

Section: Ros and Arsenic Toxicitymentioning

confidence: 99%

The Role of Reactive Oxygen Species in Arsenic Toxicity

et al. 2020

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Arsenic poisoning is a global health problem. Chronic exposure to arsenic has been associated with the development of a wide range of diseases and health problems in humans. Arsenic exposure induces the generation of intracellular reactive oxygen species (ROS), which mediate multiple changes to cell behavior by altering signaling pathways and epigenetic modifications, or cause direct oxidative damage to molecules. Antioxidants with the potential to reduce ROS levels have been shown to ameliorate arsenic-induced lesions. However, emerging evidence suggests that constructive activation of antioxidative pathways and decreased ROS levels contribute to chronic arsenic toxicity in some cases. This review details the pathways involved in arsenic-induced redox imbalance, as well as current studies on prophylaxis and treatment strategies using antioxidants.

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“…The top chemical interactor for EGR1 is particulate matter with 43 curated interactions. EGR1 has been shown to have altered gene expression in the response to environmental pollutants like arsenic [ 47 ], bisphenol A, and lead [ 48 ]. Exposure of bronchial epithelial cells to diesel particulate matter has been shown to decrease expression of EGR1 [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Environmental Epigenetics of Diesel Particulate Matter Toxicogenomics

Bilinovich

Lewis

Thompson

et al. 2020

IJERPH

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by disruptions in social communication and behavioral flexibility. Both genetic and environmental factors contribute to ASD risk. Epidemiologic studies indicate that roadway vehicle exhaust and in utero exposure to diesel particulate matter (DPM) are associated with ASD. Using the Comparative Toxicogenomics Database (CTD), we identified genes connected to DPM exposure and ASD, extracted the known enhancers/promoters of the identified genes, and integrated this with Assay for Transposase Accessible Chromatin (ATAC-seq) data from DPM-exposed human neural progenitor cells. Enhancer/promoter elements with significantly different chromosome accessibility revealed enriched DNA sequence motifs with transcription factor binding sites for EGR1. Variant extraction for linkage disequilibrium blocks of these regions followed by analysis through Genome Wide Association Studies (GWAS) revealed multiple neurological trait associations including exploratory eye movement and brain volume measurement. This approach highlights the effects of pollution on the regulatory regions of genes implicated in ASD by genetic studies, indicating convergence of genetic and environmental factors on molecular networks that contribute to ASD. Integration of publicly available data from the CTD, cell culture exposure studies, and phenotypic genetics synergize extensive evidence of chemical exposures on gene regulation for altered brain development.

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Cortex and hippocampus DNA epigenetic response to a long-term arsenic exposure via drinking water

Cited by 49 publications

References 67 publications

Decreased global DNA hydroxymethylation in neural tube defects: Association with polycyclic aromatic hydrocarbons

Decreased global DNA hydroxymethylation in neural tube defects: Association with polycyclic aromatic hydrocarbons

The Role of Reactive Oxygen Species in Arsenic Toxicity

Environmental Epigenetics of Diesel Particulate Matter Toxicogenomics

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