ArticleProceedings of the National Academy of Sciences of the United States of America1997
Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
155 citing papers in PubMed, 1 synthesis or guideline pooled it, 560 citations in OpenAlex.
- Pooled it
- High levels of circulating folate concentrations are associated with DNA methylation of tumor suppressor and repair genesClinical epigenetics · 2017Trial
- Integration of epigenetics into ecotoxicology: insights and fundamental research needs.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Arsenic induced Hippo pathway dysregulation linked to hTERT hypo-methylation in breast cancer patients.Frontiers in epigenetics and epigenomics · 2026Article
- Arsenic promotes ROS-mediated malignant transformation of bronchial epithelial cells by specifically downregulating TXNL1 expression.Communications biology · 2025Article
- Arsenome, Arsenobolome, and Arsenobiolome.International journal of molecular sciences · 2025Review
- Comorbidity of hypertension and lung cancer: interplay of genetics and environment.Discover oncology · 2025Review
- How chronic inflammation fuels carcinogenesis as an environmental epimutagen.Discover oncology · 2025Review
- Sodium arsenite-induced DNA methylation alterations exacerbated by p53 knockout in MCF7 cells.Heliyon · 2024Article
- Research progress on the regulatory mechanism of cell senescence in arsenic toxicity: a systematic review.Toxicology research · 2024Review
- Memory effects of prior subculture may impact the quality of multiomic perturbation profiles.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A dynamic model of inorganic arsenic-induced carcinogenesis reveals an epigenetic mechanism for epithelial-mesenchymal plasticity.Environmental pollution (Barking, Essex : 1987) · 2024Article
- Review
- Arsenic-induced prostate cancer: an enigma.Medical oncology (Northwood, London, England) · 2024Review
- Metabolic Carcinogenesis.Cancer treatment and research · 2024Review
- Article
- Effect of Long-Term Low-Dose Arsenic Exposure on DNA Methylation and Gene Expression in Human Liver Cells.International journal of molecular sciences · 2023Article
- Sex differences in paternal arsenic-induced intergenerational metabolic effects are mediated by estrogen.Cell & bioscience · 2023Article
- Chronic PFOA exposure in vitro causes acquisition of multiple tumor cell characteristics in rat liver cells.Toxicology in vitro : an international journal published in association with BIBRA · 2023Article
- Missing Causality and Heritability of Autoimmune Hepatitis.Digestive diseases and sciences · 2023Article
95 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inorganic arsenic, a human carcinogen, is enzymatically methylated for detoxication, consuming S-adenosyl-methionine (SAM) in the process. The fact that DNA methyltransferases (MeTases) require this same methyl donor suggests a role for methylation in arsenic carcinogenesis. Here we test the hypothesis that arsenic-induced initiation results from DNA hypomethylation caused by continuous methyl depletion. The hypothesis was tested by first inducing transformation in a rat liver epithelial cell line by chronic exposure to low levels of arsenic, as confirmed by the development of highly aggressive, malignant tumors after inoculation of cells into Nude mice. Global DNA hypomethylation occurred concurrently with malignant transformation and in the presence of depressed levels of S-adenosyl-methionine. Arsenic-induced DNA hypomethylation was a function of dose and exposure duration, and remained constant even after withdrawal of arsenic. Hyperexpressibility of the MT gene, a gene for which expression is clearly controlled by DNA methylation, was also detected in transformed cells. Acute arsenic or arsenic at nontransforming levels did not induce global hypomethylation of DNA. Whereas transcription of DNA MeTase was elevated, the MeTase enzymatic activity was reduced with arsenic transformation. Taken together, these results indicate arsenic can act as a carcinogen by inducing DNA hypomethylation, which in turn facilitates aberrant gene expression, and they constitute a tenable theory of mechanism in arsenic carcinogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.