Epigenetics in metal carcinogenesis: nickel, arsenic, chromium and cadmium

Arita, Adriana; Costa, Max

doi:10.1039/b903049b

Cited by 345 publications

(237 citation statements)

References 90 publications

(165 reference statements)

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“…For example, epigenetic variations among populations have been shown to be influenced by differences in geographic location, lifestyles and nutritional status [7]. Epigenetic mechanisms are influenced by heavy metal exposure [30], the latter often being a consequence of geographic location. Individuals from Nigeria, the country of origin for YRI, are more exposed to heavy metals than Europeans and Americans [31,32].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D receptor gene methylation is associated with ethnicity, tuberculosis, and TaqI polymorphism

et al. 2011

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The Vitamin D Receptor (VDR) gene encodes a transcription factor which, on activation by vitamin D, modulates diverse biological processes including calcium homeostasis and immune function. Genetic variation involving VDR shows striking differences in allele frequency between populations and has been associated with disease susceptibility including tuberculosis and autoimmunity, although results have often been conflicting. We hypothesized that methylation of VDR may be population specific and that the combination of differential methylation and genetic variation may characterise TB predisposition. We use bisulphite conversion and/or pyrosequencing to analyse the methylation status of 17 CpGs of VDR and to genotype 7 SNPs in the 3′ CpG Island (CGI 1060), including the commonly studied SNPs ApaI (rs7975232) and TaqI (rs731236). We show that for lymphoblastoid cell lines from two ethnically diverse populations (Yoruba from HapMap, n=30 and Caucasians, n=30) together with TB cases (n=32) and controls (n=29) from the Venda population of South Africa there are methylation variable positions (MVPs) in the 3′ end that significantly distinguish ethnicity (9/17 CpGs) and TB status (3/17 CpGs). Moreover methylation status shows complex association with TaqI genotype highlighting the need to consider both genetic and epigenetic variants in genetic studies of VDR association with disease.

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Section: Discussionmentioning

confidence: 99%

Vitamin D receptor gene methylation is associated with ethnicity, tuberculosis, and TaqI polymorphism

et al. 2011

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“…A number of studies have demonstrated that iAs exposure induces global and gene-specific post-translational histone modifications such as reduction of acetylation in histone H3 and H4: loss of H4Lys 16 10 and H2AX phosphorylation, and decreases in H2B ubiquitination (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26).…”

mentioning

confidence: 99%

Quantitative Mass Spectrometry Reveals Changes in Histone H2B Variants as Cells Undergo Inorganic Arsenic-Mediated Cellular Transformation

Rea

Eleazer

Eckstein

et al. 2016

Molecular & Cellular Proteomics

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Exposure to inorganic arsenic, a ubiquitous environmental toxic metalloid, leads to carcinogenesis. However, the mechanism is unknown. Several studies have shown that inorganic arsenic exposure alters specific gene expression patterns, possibly through alterations in chromatin structure. While most studies on understanding the mechanism of chromatin-mediated gene regulation have focused on histone post-translational modifications, the role of histone variants remains largely unknown. Incorporation of histone variants alters the functional properties of chromatin. To understand the global dynamics of chromatin structure and function in arsenic-mediated carcinogenesis, analysis of the histone variants incorporated into the nucleosome and their covalent modifications is required. Here we report the first global mass spectrometric analysis of histone H2B variants as cells undergo arsenic-mediated epithelial to mesenchymal transition. We used electron capture dissociation-based top-down tandem mass spectrometry analysis validated with quantitative reverse transcription real-time polymerase chain reaction to identify changes in the expression levels of H2B variants in inorganic arsenic-mediated epithelial-mesenchymal transition. We identified changes in the expression levels of specific histone H2B variants in two cell types, which are dependent on dose and length of exposure of inorganic arsenic. In particular, we found increases in H2B variants H2B1H/1K/1C/1J/1O and H2B2E/2F, and significant decreases in H2B1N/1D/1B as cells undergo inorganic arsenic-mediated epithelial-mesenchymal transition. The analysis of these histone vari-

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“…However, the effect of Cd in carcinogenesis has not been studied in relation to DNA hydroxymethylation, which would enable a better understanding of Cd exposed carcinogenesis [98]. A similar effect of heavy metals on IDH, SDH and FH inhibition may throw light on alternate 5hmC deregulation mode of carcinogenesis.…”

Section: Heavy Metals Deregulate 5-hydroxymethylcytosinementioning

confidence: 99%

Regulation and Functional Significance of 5-Hydroxymethylcytosine in Cancer

et al. 2017

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Epigenetic modes of gene regulation are important for physiological conditions and its aberrant changes can lead to disease like cancer. 5-hydroxymethylcytosine (5hmC) is an oxidized form of 5-methylcytosine (5mC) catalyzed by Ten Eleven Translocation (TET) enzymes. 5hmC is considered to be a demethylation intermediate and is emerging as a stable and functional base modification. The global loss of 5hmC level is commonly observed in cancers and tumorigenic germline mutations in IDH, SDH and FH are found to be inhibiting TET activity. Although a global loss of 5hmC is characteristic in cancers, locus-specific 5hmC gain implicates selective gene expression control. The definitive role of 5hmC as a tumor suppressing or promoting modification can be deduced by identifying locus-specific 5hmC modification in different types of cancer. Determining the genes carrying 5hmC modifications and its selective variation will open up new therapeutic targets. This review outlines the role of global and locus-specific changes of 5hmC in cancers and the possible mechanisms underlying such changes. We have described major cellular factors that influence 5hmC levels and highlighted the significance of 5hmC in tumor micro environmental condition like hypoxia.

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Epigenetics in metal carcinogenesis: nickel, arsenic, chromium and cadmium

Cited by 345 publications

References 90 publications

Vitamin D receptor gene methylation is associated with ethnicity, tuberculosis, and TaqI polymorphism

Vitamin D receptor gene methylation is associated with ethnicity, tuberculosis, and TaqI polymorphism

Quantitative Mass Spectrometry Reveals Changes in Histone H2B Variants as Cells Undergo Inorganic Arsenic-Mediated Cellular Transformation

Regulation and Functional Significance of 5-Hydroxymethylcytosine in Cancer

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