Arsenic‐Induced Changes to the Epigenome

Bailey, Kathryn A.; Fry, Rebecca C.

doi:10.1002/9781118349045.ch8

Cited by 11 publications

(18 citation statements)

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“…Previous reviews have highlighted that most studies of the effects of arsenical exposure on miRNAs have been performed in vitro , and few have investigated the functional consequences of these perturbations [22, 23]. In recent years, in vitro studies have continued to predominate, but many are mechanistic in nature, in which miRNAs have been implicated in mediating various toxic effects of arsenicals (Table 3).…”

Section: Arsenic and Micrornas (Mirnas)mentioning

confidence: 99%

“…Previous reviews have emphasized the following general findings associated with arsenical exposure: (1) both global and gene-specific changes in DNA methylation levels have been observed, (2) histones are targeted for post-translational modifications, and (3) miRNA levels are perturbed [22–24]. In the present review, we expand upon this information and synthesize and evaluate the current state of knowledge of arsenic-associated epigenetic modifications, particularly in the context of their biological significance in disease development.…”

Section: Introductionmentioning

confidence: 99%

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Arsenic-Associated Changes to the Epigenome: What Are the Functional Consequences?

Bailey

Fry

2014

Curr Envir Health Rpt

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Inorganic arsenic (iAs) poses a major threat to worldwide human health, and yet the molecular mechanisms underlying the toxic effects associated with iAs exposure are not well understood. There is increasing experimental evidence indicating that epigenetic modifications may play a major role in the development of diseases associated with exposure to environmental toxicants. Research in the field has firmly established that iAs exposure is associated with epigenetic alterations including changes in DNA methylation, miRNA abundance, and post-translational histone modifications. Here, we summarize recent studies that have expanded the current knowledge of these relationships. These studies have pinpointed specific regions of the genome and genes that are targets of arsenical-induced epigenetic changes, including those associated with in utero iAs exposure. The recent literature indicates that iAs biotransformation likely plays an important role in the relationship between iAs exposure and the epigenome, in addition to the sex and genetic background of individuals. The research also shows that relatively low to moderate exposure to iAs is associated with epigenetic effects. However, while it is well established that arsenicals can alter components of the epigenome, in many cases, the biological significance of these alterations remains unknown. The manner by which these and future studies may help inform the role of epigenetic modifications in the development of iAs-associated disease is evaluated and the need for functional validation emphasized.

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Section: Arsenic and Micrornas (Mirnas)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Arsenic-Associated Changes to the Epigenome: What Are the Functional Consequences?

Bailey

Fry

2014

Curr Envir Health Rpt

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“…DNA methylation patterns are tissue specific, and one critical limitation for human epigenetic studies is that tissues that are relevant for disease etiology cannot be easily obtained in most cases from patients and study participants (Baccarelli et al, 2012; Terry et al, 2011). Human in vivo studies of DNA methylation have often used blood (Tarantini et al, 2009; Bacarelli et al, 2009; Hou et al, 2010; Wright et al, 2010; Bailey KA et al, 2012; Bollati et al, 2009) or buccal cells as easily obtainable specimens in patients as well as in healthy individuals (Baccarelli et al, 2012). Characterizing methylation signatures in DNA from peripheral blood may have important implications as a biomarker for early diagnosis and prognosis (Qiu, et al, 2012; Terry et al, 2011).…”

Section: Discusionmentioning

confidence: 99%

DNA methylation of extracellular matrix remodeling genes in children exposed to arsenic

Gonzalez-Cortes

Recio-Vega

Lantz

et al. 2017

Toxicology and Applied Pharmacology

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Several novel mechanistic findings regarding to arsenic’s pathogenesis has been reported and some of them suggest that the etiology of some arsenic induced diseases are due in part to heritable changes to the genome via epigenetic processes such as DNA methylation, histone maintenance, and mRNA expression. Recently, we reported that arsenic exposure during in utero and early life was associated with impairment in the lung function and abnormal receptor for advanced glycation endproducts (RAGE), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) sputum levels. Based on our results and the reported arsenic impacts on DNA methylation, we designed this study in our cohort of children exposed in utero and early childhood to arsenic with the aim to associate DNA methylation of MMP9, TIMP1 and RAGE genes with its protein sputum levels and with urinary and toenail arsenic levels. The results disclosed hypermethylation in MMP9 promotor region in the most exposed children; and an increase in the RAGE sputum levels among children with the mid methylation grade; there were also positive associations between MMP9 DNA methylation with arsenic toenail concentrations; RAGE DNA methylation with iAs, and %DMA; and finally between TIMP1 DNA methylation with the first arsenic methylation. A negative correlation between MMP9 sputum levels with its DNA methylation was registered. In conclusion, arsenic exposure during in utero and early life modifies DNA methylation in the evaluated genes. This may contribute to abnormal extracellular matrix remodeling genes expression altering protein levels with a subsequent lung function impairment.

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“…Arsenic exposure and effects on DNA methylation have been studied in vitro , in vivo , and within human populations, as reviewed in [13], yet the biological consequences of the observed changes have not been established. In addition, a causal relationship between iAs exposure, DNA methylation changes, and oncogenesis has not been established.…”

Section: Toxic Metal Exposure and Epigeneticsmentioning

confidence: 99%

“…The long-term health consequences associated with prenatal iAs exposure support that iAs may exert its effects through epigenetic mechanisms as it is not a mutagen. The effects of chronic iAs exposure and development of disease are more extensively described by Bailey and Fry [13]. …”

Section: Toxic Metal Exposure and Epigeneticsmentioning

confidence: 99%

Investigating Epigenetic Effects of Prenatal Exposure to Toxic Metals in Newborns: Challenges and Benefits

et al. 2014

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Increasing evidence suggests that epigenetic alterations can have a great impact on human health, and that epigenetic mechanisms (DNA methylation, histone modifications, and microRNAs) may be particularly relevant in responding to environmental toxicant exposure early in life. The epigenome plays a vital role in embryonic development, tissue differentiation, and development of disease by controlling gene expression. In this review, we discuss what is currently known about epigenetic alterations in response to prenatal exposure to inorganic arsenic (iAs) and lead (Pb), focusing specifically on their effects on DNA methylation. We then describe how epigenetic alterations are studied in newborns as potential biomarkers of in utero environmental toxicant exposure, and the benefits and challenges of this approach. In summary, the studies highlighted herein indicate how epigenetic mechanisms have an impact on early-life exposure to iAs and Pb and the research that is being done to move towards an understanding of the relationships between toxicant-induced epigenetic alterations and disease development. Although much remains unknown, several groups are working to understand the correlative and causal effects of early-life toxic metal exposure on epigenetic changes and to find out how these may result in later disease development.

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Arsenic‐Induced Changes to the Epigenome

Cited by 11 publications

References 184 publications

Arsenic-Associated Changes to the Epigenome: What Are the Functional Consequences?

Arsenic-Associated Changes to the Epigenome: What Are the Functional Consequences?

DNA methylation of extracellular matrix remodeling genes in children exposed to arsenic

Investigating Epigenetic Effects of Prenatal Exposure to Toxic Metals in Newborns: Challenges and Benefits

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