Arsenic exposure from drinking water is associated with decreased gene expression and increased DNA methylation in peripheral blood

Ameer, Syeda Shegufta; Engström, Karin; Hossain, Mohammad Bakhtiar; Concha, Gabriela; Vahter, Marie; Broberg, Karin

doi:10.1016/j.taap.2017.02.019

Cited by 42 publications

(22 citation statements)

References 71 publications

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“…2019 ). In addition, in a study of women in Argentina (

), differential methylation was found at 6 loci ( Ameer et al. 2017 ), and in a study of families in China (adults and children;

), differential methylation was found at 85 loci ( Guo et al.…”

Section: Discussionmentioning

confidence: 99%

“…Studies of adult populations have included cohorts in Bangladesh, identifying 4 CpGs associated with As measured in urine or blood at p Bonferroni < 0:05 (n = 400; 3 CpGs overlapped for both exposure measures) (Argos et al 2015) and 50 CpGs associated with As measured in urine or drinking water at FDR < 0:05 (n = 396; 8 CpGs overlapped for both exposure measures) (Demanelis et al 2019). In addition, in a study of women in Argentina (n = 93), differential methylation was found at 6 loci (Ameer et al 2017), and in a study of families in China (adults and children; n = 102), differential methylation was found at 85 loci (Guo et al 2018). To understand the overlap between loci previously identified as differentially methylated with As exposure, we used a lookup approach of studies analyzing the association between As exposure and DNA methylation measured using the 450K or 850K microarrays.…”

Section: Environmental Health Perspectivesmentioning

confidence: 91%

“…Inconsistent results among epidemiological studies of the association between As exposure and epigenetic dysregulation may be due to differences between populations studied (e.g., age, sex, genetic structure), levels of As exposure, differential residual confounding, and methods for quantifying DNA methylation (Argos 2015). Previous EWAS of As exposure have included birth cohorts in the United States (Green et al 2016;Koestler et al 2013), Bangladesh (Broberg et al 2014;Cardenas et al 2015;Gliga et al 2018;Kile et al 2012), Mexico (Rojas et al 2015), and Taiwan (Kaushal et al 2017), and studies of adults in the United States , Bangladesh (Argos et al 2015;Demanelis et al 2019), Argentina (Ameer et al 2017), and China (Guo et al 2018). In addition, the samples sizes of previous EWAS have ranged from <50-400, resulting in limited statistical, particularly when interrogating a large number of CpG sites (Argos 2015).…”

Section: Introductionmentioning

confidence: 99%

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Locus-Specific Differential DNA Methylation and Urinary Arsenic: An Epigenome-Wide Association Study in Blood among Adults with Low-to-Moderate Arsenic Exposure

Bozack

Domingo‐Relloso

Haack

et al. 2020

Environ Health Perspect

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BACKGROUND: Chronic exposure to arsenic (As), a human toxicant and carcinogen, remains a global public health problem. Health risks persist after As exposure has ended, suggesting epigenetic dysregulation as a mechanistic link between exposure and health outcomes. OBJECTIVES: We investigated the association between total urinary As and locus-specific DNA methylation in the Strong Heart Study, a cohort of American Indian adults with low-to-moderate As exposure [total urinary As, mean ð±SDÞ lg=g creatinine: 11.7 (10.6)]. METHODS: DNA methylation was measured in 2,325 participants using the Illumina MethylationEPIC array. We implemented linear models to test differentially methylated positions (DMPs) and the DMRcate method to identify regions (DMRs) and conducted gene ontology enrichment analysis. Models were adjusted for estimated cell type proportions, age, sex, body mass index, smoking, education, estimated glomerular filtration rate, and study center. Arsenic was measured in urine as the sum of inorganic and methylated species. RESULTS: In adjusted models, methylation at 20 CpGs was associated with urinary As after false discovery rate (FDR) correction (FDR < 0:05). After Bonferroni correction, 5 CpGs remained associated with total urinary As (p Bonferroni < 0:05), located in SLC7A11, ANKS3, LINGO3, CSNK1D, ADAMTSL4. We identified one DMR on chromosome 11 (chr11:2,322,050-2,323,247), annotated to C11orf2; TSPAN32 genes. DISCUSSION: This is one of the first epigenome-wide association studies to investigate As exposure and locus-specific DNA methylation using the Illumina MethylationEPIC array and the largest epigenome-wide study of As exposure. The top DMP was located in SLC7A11A, a gene involved in cystine/glutamate transport and the biosynthesis of glutathione, an antioxidant that may protect against As-induced oxidative stress. Additional DMPs were located in genes associated with tumor development and glucose metabolism. Further research is needed, including research in more diverse populations, to investigate whether As-related DNA methylation signatures are associated with gene expression or may serve as biomarkers of disease development.

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“…2019 ). In addition, in a study of women in Argentina (

), differential methylation was found at 6 loci ( Ameer et al. 2017 ), and in a study of families in China (adults and children;

), differential methylation was found at 85 loci ( Guo et al.…”

Section: Discussionmentioning

confidence: 99%

Section: Environmental Health Perspectivesmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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Locus-Specific Differential DNA Methylation and Urinary Arsenic: An Epigenome-Wide Association Study in Blood among Adults with Low-to-Moderate Arsenic Exposure

Bozack

Domingo‐Relloso

Haack

et al. 2020

Environ Health Perspect

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“…Two other reports suggest that arsenic reduces whole DNA 5-methylcytosine methylation levels in the bladders [ 12 , 33 ]. In contrast, one report indicates that an increased arsenic exposure is associated with a lower gene expression and hypermethylation in human peripheral blood [ 34 ]. Because the reprogrammed DNA methylation would induce gene expression change, the effect of arsenic on the DNA methylation of mouse urothelium may be one of the causes contributing to the promotion of BBN-induced carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

The interaction of arsenic and N-butyl-N-(4-hydroxybutyl)nitrosamine on urothelial carcinogenesis in mice

et al. 2017

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The bladder is an important organ for the storage of excreted water and metabolites. If metabolites with carcinogenic characteristics are present in urine, the urothelial lining of the bladder could be damaged and genetically altered. In this study, we analyzed the interaction of arsenic and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) on mouse bladder carcinogenesis. Our previous study found that arsenic affects BBN-altered urothelial enzymatic activity, protein expression, DNA oxidation and global DNA CpG methylation levels. In this study, two mouse models were used. First, after administering a co-treatment of BBN and arsenic for 20 weeks, BBN alone led to a urothelial carcinoma formation of 20%, and arsenic promoted a BBN-induced urothelial carcinoma formation of 10%. The protein expression of GSTM1, GSTO1, NQO1, and p21 did not change by arsenic along with the BBN co-treatment, but the Sp1 expression increased. In the second mouse model, BBN was a pretreatment promoter; arsenic dose-dependently deteriorated BBN-promoted dysplasia by 10% and 40% at 10 ppm and 100 ppm, respectively. Conversely, BBN pretreatment also accelerated arsenic-induced dysplasia by 30%. The urothelial carcinogenic effect reversed after ceasing BBN for a period of 20 weeks. In summary, three conclusions were drawn from this study. The first is the mutual promotion of arsenic and BBN in bladder carcinogenesis. Second, arsenic dosages without bladder carcinogenicity (10 ppm) or with slight carcinogenicity (100 ppm) promote BBN-induced mice bladder cancer progression. Finally, the dysplastic urothelium had reverted to near-normal morphology after ceasing BBN intake for 20 weeks, providing a good suggestion for people who want to quit smoking.

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“…[2] Exposure to arsenic may cause reduced IQ in children, as well as cause bladder and lung cancer, and skin and circulatory system damage. [3] As many as 200 million people are exposed to drinking water with arsenic concentrations that exceed the WHO guideline of 10 ppb. [4] In some countries, measured arsenic concentrations in contaminated ground water have been observed at levels up to 1000 ppb.…”

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confidence: 99%

A Highly Sensitive Enzymatic Catalysis System for Trace Detection of Arsenic in Water

Liu

Cao

et al. 2017

Chemistry A European J

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Arsenic (As) is an extremely toxic element that exists in the environment in different chemical forms. The detection of arsenic in potable water remains a challenging task. This study presents a highly sensitive enzymatic catalysis system for trace sensing of inorganic arsenic in water. This is the first enzyme-catalyzed fluorescence assay capable of detecting arsenic at concentrations below the allowable level adopted by the World Health Organization (10 ppb in drinking water). The enzyme catalytically produces fluorescent NADH in the presence of arsenate, which enables facile detection of arsenate at concentrations in the 0 – 200 ppb range. Calibration curves made at a set time interval allow accurate determination of unknown arsenic samples. This method holds potential for interfacing with automated analytical sampling systems to allow arsenic determinations in environmental health applications.

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Arsenic exposure from drinking water is associated with decreased gene expression and increased DNA methylation in peripheral blood

Cited by 42 publications

References 71 publications

Locus-Specific Differential DNA Methylation and Urinary Arsenic: An Epigenome-Wide Association Study in Blood among Adults with Low-to-Moderate Arsenic Exposure

Locus-Specific Differential DNA Methylation and Urinary Arsenic: An Epigenome-Wide Association Study in Blood among Adults with Low-to-Moderate Arsenic Exposure

The interaction of arsenic and N-butyl-N-(4-hydroxybutyl)nitrosamine on urothelial carcinogenesis in mice

A Highly Sensitive Enzymatic Catalysis System for Trace Detection of Arsenic in Water

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