ArticleEnvironmental and molecular mutagenesis2016
Dysregulation of DNA methylation induced by past arsenic treatment causes persistent genomic instability in mammalian cells.
Article in Environmental and molecular mutagenesis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Effects of anthropogenic influences in the DNA methylation and expression of genes involved in the metabolism of Geophagus surinamensis from the Pará River (Amazon, Brazil).Ecotoxicology (London, England) · 2026Article
- Impact of Arsenite on Transient and Persistent Histone H3 Modifications and Transcriptional Response.Chemical research in toxicology · 2026Article
- Metal carcinogens and cancer: integrating genetic and epigenetic perspectives.Frontiers in oncology · 2026Review
- Article
- Changes in Energy Dynamics in Arsenic Exposure based Neurotoxicity: A Comprehensive Review.Current medicinal chemistry · 2025Review
- Mechanisms of genotoxicity and proteotoxicity induced by the metalloids arsenic and antimony.Cellular and molecular life sciences : CMLS · 2023Review
- Nutritional epigenomic and DNA-damage modulation effect of natural stilbenoids.Scientific reports · 2023Article
- Arsenic and cancer: Evidence and mechanisms.Advances in pharmacology (San Diego, Calif.) · 2023Article
- Exposure of pigs to glyphosate affects gene-specific DNA methylation and gene expression.Toxicology reports · 2022Article
- Arsenic co-carcinogenesis: Inhibition of DNA repair and interaction with zinc finger proteins.Seminars in cancer biology · 2021Review
- Connections between endoplasmic reticulum stress-associated unfolded protein response, mitochondria, and autophagy in arsenic-induced carcinogenesis.Seminars in cancer biology · 2021Review
- Nutrition, one-carbon metabolism and arsenic methylation.Toxicology · 2021Review
- Health Effects Associated With Pre- and Perinatal Exposure to Arsenic.Frontiers in genetics · 2021Review
- Article
- A review of arsenic exposure and lung cancer.Toxicology research · 2019Review
- Arsenic‑induced BRCA1 CpG promoter methylation is associated with the downregulation of ERα and resistance to tamoxifen in MCF7 breast cancer cells and mouse mammary tumor xenografts.International journal of oncology · 2019Article
- State of the science review of the health effects of inorganic arsenic: Perspectives for future research.Environmental toxicology · 2019Review
- The Impact of Long-term Exposure to Low Levels of Inorganic Arsenic on the Hypomethylation of SEPT9 Promoter in Epithelial-Mesenchymal Transformed Colorectal Cancer Cell Lines.International journal of molecular and cellular medicine · 2019Article
- Nutritional Influences on One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity.Annual review of nutrition · 2018Review
- Methylation of cytokines gene promoters in IL-1β-treated human intestinal epithelial cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The mechanisms by which arsenic-induced genomic instability is initiated and maintained are poorly understood. To investigate potential epigenetic mechanisms, in this study we evaluated global DNA methylation levels in V79 cells and human HaCaT keratinocytes at several time points during expanded growth of cell cultures following removal of arsenite exposures. We have found altered genomic methylation patterns that persisted up to 40 cell generations in HaCaT cells after the treatments were withdrawn. Moreover, mRNA expression levels were evaluated by RT-PCR for DNMT1, DNMT3A, DNMT3B, HMLH1, and HMSH2 genes, demonstrating that the down regulation of DNMT3A and DNMT3B genes, but not DNMT1, occurred in an arsenic dose-dependent manner, and persisted for many cell generations following removal of the arsenite, offering a plausible mechanism of persistently genotoxic arsenic action. Analyses of promoter methylation status of the DNA mismatch repair genes HMLH1 and HMSH2 show that HMSH2, but not HMLH1, was epigenetically regulated by promoter hypermethylation changes following arsenic treatment. The results reported here demonstrate that arsenic exposure promptly induces genome-wide global DNA hypomethylation, and some specific gene promoter methylation changes, that persist for many cell generations following withdrawal of arsenite, supporting the hypothesis that the cells undergo epigenetic reprogramming at both the gene and genome level that is durable over many cell generations in the absence of further arsenic treatment. These DNA methylation changes, in concert with other known epigenome alterations, are likely contributing to long-lasting arsenic-induced genomic instability that manifests in several ways, including aberrant chromosomal effects.
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Registered trials
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