Arsenic Biotransformation as a Cancer Promoting Factor by Inducing DNA Damage and Disruption of Repair Mechanisms

Chronic exposure to arsenic in drinking water poses a major global health concern. Populations exposed to high concentrations of arsenic-contaminated drinking water suffer serious health consequences, including alarming cancer incidence and death rates. Arsenic is biotransformed through sequential addition of methyl groups, acquired from s-adenosylmethionine (SAM). Metabolism of arsenic generates a variety of genotoxic and cytotoxic species, damaging DNA directly and indirectly, through the generation of reactive oxidative species and induction of DNA adducts, strand breaks and cross links, and inhibition of the DNA repair process itself. Since SAM is the methyl group donor used by DNA methyltransferases to maintain normal epigenetic patterns in all human cells, arsenic is also postulated to affect maintenance of normal DNA methylation patterns, chromatin structure, and genomic stability. The biological processes underlying the cancer promoting factors of arsenic metabolism, related to DNA damage and repair, will be discussed here.

• Publication year

  2011

• Venue

  Molecular Biology International

• Publication date

  2011-08-02

• Fields of study

  Biology, Medicine, Chemistry, Environmental Science

• Identifiers
  DOI 10.4061/2011/718974PMID 22091411PMCID 3200225
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Arsenic-induced oxidative stress and its reversibility.

  2011cited by this paper
• Chronic exposure to arsenic causes increased cell survival, DNA damage, and increased expression of mitochondrial transcription factor A (mtTFA) in human prostate epithelial cells.

  2011influential reference
• Cytogenetic insights into DNA damage and repair of lesions induced by a monomethylated trivalent arsenical.

  2010cited by this paper
• Arsenic-induced carcinogenesis--oxidative stress as a possible mode of action and future research needs for more biologically based risk assessment.

  2010cited by this paper
• Arsenic-related DNA copy-number alterations in lung squamous cell carcinomas

  2010cited by this paper
• Age and exposure to arsenic alter base excision repair transcript levels in mice.

  2010cited by this paper
• Requirement of arsenic biomethylation for oxidative DNA damage.

  2009cited by this paper
• Biomarkers of oxidative stress and damage in human populations exposed to arsenic.

  2009cited by this paper
• Sodium arsenite induces ROS generation, DNA oxidative damage, HO-1 and c-Myc proteins, NF-kappaB activation and cell proliferation in human breast cancer MCF-7 cells.

  2009cited by this paper
• Elevated ERCC1 gene expression in blood cells associated with exposure to arsenic from drinking water in Inner Mongolia.

  2009cited by this paper
• BRCA2-dependent homologous recombination is required for repair of Arsenite-induced replication lesions in mammalian cells

  2009cited by this paper
• Comparative genomic hybridization study of arsenic-exposed and non-arsenic-exposed urinary transitional cell carcinoma.

  2008cited by this paper
• Tissue distribution and urinary excretion of inorganic arsenic and its methylated metabolites in C57BL6 mice following subchronic exposure to arsenate in drinking water.

  2008cited by this paper
• Modulation of DNA polymerase beta-dependent base excision repair in cultured human cells after low dose exposure to arsenite.

  2008influential reference
• Evidence against the nuclear in situ binding of arsenicals--oxidative stress theory of arsenic carcinogenesis.

  2008cited by this paper
• Low concentration of arsenite exacerbates UVR-induced DNA strand breaks by inhibiting PARP-1 activity.

  2008cited by this paper
• Arsenic induced mitochondrial DNA damage and altered mitochondrial oxidative function: implications for genotoxic mechanisms in mammalian cells.

  2007cited by this paper
• Altered poly(ADP-ribose) metabolism impairs cellular responses to genotoxic stress in a hypomorphic mutant of poly(ADP-ribose) glycohydrolase.

  2007cited by this paper
• Insights into the carcinogenic mode of action of arsenic.

  2007cited by this paper
• DNA polymerase δ-dependent repair of DNA single strand breaks containing 3′-end proximal lesions

  2007cited by this paper
• Poly(ADP-Ribose) Polymerase 1 Accelerates Single-Strand Break Repair in Concert with Poly(ADP-Ribose) Glycohydrolase

  2007cited by this paper
• Genetic and epigenetic changes induced by chronic low dose exposure to arsenic of mouse testicular Leydig cells.

  2007cited by this paper
• Oxidative stress and cancer: have we moved forward?

  2007cited by this paper
• Mutation at the Polymerase Active Site of Mouse DNA Polymerase δ Increases Genomic Instability and Accelerates Tumorigenesis

  2007cited by this paper
• Lung cancer in never smokers — a different disease

  2007cited by this paper
• Fifty-year study of lung and bladder cancer mortality in Chile related to arsenic in drinking water.

  2007cited by this paper
• DNA double-strand break repair: from mechanistic understanding to cancer treatment.

  2007cited by this paper
• Cytogenetically balanced translocations are associated with focal copy number alterations

  2007cited by this paper
• Blindness Survey Methods: Response from Sudan Study Authors

  2007cited by this paper
• Poly(ADP-ribose): novel functions for an old molecule

  2006cited by this paper
• Arsenic Exposure Is Associated with Decreased DNA Repair in Vitro and in Individuals Exposed to Drinking Water Arsenic

  2006cited by this paper
• Role of Oxidative Stress in Arsenic-Induced Toxicity

  2006cited by this paper
• High resolution analysis of non‐small cell lung cancer cell lines by whole genome tiling path array CGH

  2006cited by this paper
• Free radicals, metals and antioxidants in oxidative stress-induced cancer.

  2006cited by this paper
• Chronic Arsenic Exposure and Oxidative Stress: OGG1 Expression and Arsenic Exposure, Nail Selenium, and Skin Hyperkeratosis in Inner Mongolia

  2006cited by this paper
• The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer.

  2006cited by this paper
• Induction of DNA strand breaks, DNA-protein crosslinks and sister chromatid exchanges by arsenite in a human lung cell line.

  2006cited by this paper
• Specific induction of oxidative stress in terminal bronchiolar Clara cells during dimethylarsenic-induced lung tumor promoting process in mice.

  2005cited by this paper
• High-resolution genomic profiles of human lung cancer.

  2005cited by this paper
• Ageing and PARP.

  2005cited by this paper
• Comutagenesis of sodium arsenite with ultraviolet radiation in Chinese hamster V79 cells

  2005cited by this paper
• Lack of poly(ADP-ribose) polymerase-1 gene product enhances cellular sensitivity to arsenite.

  2005cited by this paper
• A new metabolic pathway of arsenite: arsenic–glutathione complexes are substrates for human arsenic methyltransferase Cyt19

  2005cited by this paper
• Mitochondrial damage mediates genotoxicity of arsenic in mammalian cells.

  2005cited by this paper
• Arsenic: In Search of an Antidote to a Global Poison

  2005cited by this paper
• Architectural Role of Mitochondrial Transcription Factor A in Maintenance of Human Mitochondrial DNA

  2004cited by this paper
• The genetics of geochemistry.

  2004cited by this paper
• DNA single-strand breaks and neurodegeneration.

  2004cited by this paper
• Mitochondrial transcription factor A regulates mtDNA copy number in mammals.

  2004cited by this paper
• Arsenic induces oxidative DNA damage in mammalian cells

  2004cited by this paper
• Oxidative mechanism of arsenic toxicity and carcinogenesis

  2004cited by this paper
• Immunohistochemical analysis of oxidative DNA damage in arsenic-related human skin samples from arsenic-contaminated area of China.

  2004cited by this paper
• Arsenic drinking water exposure and urinary excretion among adults in the Yaqui Valley, Sonora, Mexico.

  2004cited by this paper
• FAST TRACK DECREASED DNA REPAIR GENE EXPRESSION AMONG INDIVIDUALS EXPOSED TO ARSENIC IN UNITED STATES DRINKING WATER

  2003cited by this paper
• Regulation of redox and DNA repair genes by arsenic: Low dose protection against oxidative stress?

  2003cited by this paper
• Arsenite and its biomethylated metabolites interfere with the formation and repair of stable BPDE-induced DNA adducts in human cells and impair XPAzf and Fpg.

  2003cited by this paper
• Effects of arsenic on telomerase and telomeres in relation to cell proliferation and apoptosis in human keratinocytes and leukemia cells in vitro.

  2003cited by this paper
• Poly(ADP-ribose) Polymerase-1 (PARP-1) Is Required in Murine Cell Lines for Base Excision Repair of Oxidative DNA Damage in the Absence of DNA Polymerase β*

  2003cited by this paper
• Highly oxidised gold skarn fluids evolution in the Mezcala deposit, Guerrero, Mexico

  2003cited by this paper
• Oxidative stress as a possible mode of action for arsenic carcinogenesis.

  2003cited by this paper
• Oxidative DNA damage following exposure to dimethylarsinous iodide: the formation of cis-thymine glycol.

  2003cited by this paper
• Mechanism of arsenic carcinogenesis: an integrated approach.

  2003cited by this paper
• Modulation of DNA repair processes by arsenic and selenium compounds.

  2003cited by this paper
• Methylated trivalent arsenicals as candidate ultimate genotoxic forms of arsenic: Induction of chromosomal mutations but not gene mutations

  2003cited by this paper
• Plasmid DNA damage caused by methylated arsenicals, ascorbic acid and human liver ferritin.

  2002cited by this paper
• Worldwide Occurrences of Arsenic in Ground Water

  2002cited by this paper
• Induction of DNA polymerase beta-dependent base excision repair in response to oxidative stress in vivo.

  2002cited by this paper
• Arsenic trioxide induces apoptosis through a reactive oxygen species-dependent pathway and loss of mitochondrial membrane potential in HeLa cells.

  2002cited by this paper
• Arsenic-related chromosomal alterations in bladder cancer.

  2002cited by this paper
• A review of the source, behaviour and distribution of arsenic in natural waters

  2002cited by this paper
• Skin manifestations of arsenicosis in two villages in Bangladesh

  2002cited by this paper
• High incidence of epithelial cancers in mice deficient for DNA polymerase δ proofreading

  2002cited by this paper
• Coordination of altered DNA repair and damage pathways in arsenite-exposed keratinocytes.

  2002cited by this paper
• A NovelS-Adenosyl-l-methionine:Arsenic(III) Methyltransferase from Rat Liver Cytosol*

  2002cited by this paper
• Methylated trivalent arsenic species are genotoxic.

  2001cited by this paper
• Genetic toxicology of a paradoxical human carcinogen, arsenic: a review.

  2001cited by this paper
• Oral administration of dimethylarsinic acid, a main metabolite of inorganic arsenic, in mice promotes skin tumorigenesis initiated by dimethylbenz(a)anthracene with or without ultraviolet B as a promoter.

  2001cited by this paper
• Role of metabolism in arsenic toxicity.

  2001cited by this paper
• Identification of dimethylarsinous and monomethylarsonous acids in human urine of the arsenic-affected areas in West Bengal, India.

  2001cited by this paper
• Induction of oxyradicals by arsenic: implication for mechanism of genotoxicity.

  2001influential reference
• Stress-related gene expression in mice treated with inorganic arsenicals.

  2001cited by this paper
• Base excision repair is impaired in mammalian cells lacking Poly(ADP-ribose) polymerase-1.

  2000cited by this paper
• Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells

  2000cited by this paper
• Nucleotide excision repair and human syndromes.

  2000cited by this paper
• Mechanisms of arsenic carcinogenicity: genetic or epigenetic mechanisms?

  2000cited by this paper
• Lung Cancer and Arsenic Concentrations in Drinking Water in Chile

  2000cited by this paper
• Genetic polymorphism in the biotransformation of inorganic arsenic and its role in toxicity.

  2000cited by this paper
• Monomethylarsonous acid (MMA(III)) is more toxic than arsenite in Chang human hepatocytes.

  2000cited by this paper
• Risk of internal cancers from arsenic in drinking water.

  2000cited by this paper
• Arsenic species that cause release of iron from ferritin and generation of activated oxygen.

  2000cited by this paper
• DNA damage in arsenite- and cadmium-treated bovine aortic endothelial cells.

  2000cited by this paper
• Poly(ADP-ribose) polymerase-1: what have we learned from the deficient mouse model?

  2000cited by this paper
• Occurrence of monomethylarsonous acid in urine of humans exposed to inorganic arsenic.

  2000cited by this paper
• The role of orally administered dimethylarsinic acid, a main metabolite of inorganic arsenics, in the promotion and progression of UVB-induced skin tumorigenesis in hairless mice.

  2000cited by this paper
• Base excision repair in yeast and mammals.

  2000cited by this paper
• Modulation of base excision repair by low density lipoprotein, oxidized low density lipoprotein and antioxidants in mouse monocytes.

  2000cited by this paper
• Modulation of DNA Repair and Glutathione Levels in Human Keratinocytes by Micromolar Arsenite

  1999cited by this paper
• The Department of Health and Human Services.

  1999cited by this paper
• The role of oxidative DNA damage in human arsenic carcinogenesis: detection of 8-hydroxy-2'-deoxyguanosine in arsenic-related Bowen's disease.

  1999cited by this paper
• Stimulation of reactive oxygen, but not reactive nitrogen species, in vascular endothelial cells exposed to low levels of arsenite.

  1999cited by this paper

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• Can quercetin reduce arsenic induced toxicity in mouse BALB/c 3T3 fibroblast cells? A study involving in vitro, molecular docking, and ADME predictions

  2025cites this paper
• Synergic effect of arsenic exposure related methylation changes in three cohorts exposed to levels of this toxicant

  2025cites this paper
• Arsenome, Arsenobolome, and Arsenobiolome

  2025cites this paper
• Risk assessment of As, Cd, Cr, and Pb via the consumption of seafood in Haikou

  2024cites this paper
• Effects of Prenatal Exposure to Arsenic on T Cell Development in Children

  2023cites this paper
• Chromosomal aberration and genetic differentiation of Oreochromis niloticus affected by heavy metals from an iron ore mine area

  2022cites this paper
• A Review on Detection Techniques, Health Hazards and Human Health Risk Assessment of Arsenic Pollution in Soil and Groundwater

  2022cites this paper
• CHD4 plays a critical role in arsenite-induced oxidative damage in human urothelial carcinoma.

  2022cites this paper
• A Comprehensive Transcriptomic Analysis of Arsenic-Induced Bladder Carcinogenesis

  2022cites this paper
• Arsenic Exposure through Dietary Intake and Associated Health Hazards in the Middle East

  2022cites this paper
• Differential metabolism of arsenicals regulates Fps1-mediated arsenite transport

  2022cites this paper
• Arsenic as an environmental and human health antagonist: A review of its toxicity and disease initiation.

  2022cites this paper
• Transgenerational effects in DNA methylation, genotoxicity and reproductive phenotype by chronic arsenic exposure

  2021cites this paper
• Different mechanisms of arsenic related signaling in cellular proliferation, apoptosis and neo-plastic transformation.

  2021cites this paper
• Role of Arsenic in Carcinogenesis

  2021cites this paper
• Polymorphisms of the AS3MT gene are associated with arsenic methylation capacity and damage to the P21 gene in arsenic trioxide plant workers

  2021influential citation
• Predicting the Outcome of Arsenic Toxicity on Exposed Juvenile Male-Humans: A Shift to Infertility

  2021cites this paper
• Reproductive Toxicity of Arsenic: What We Know and What We Need to Know?

  2021cites this paper
• An arsenic stress signaling code in yeast

  2021cites this paper
• Intergenerational and transgenerational effects of environmental factors and a role for the epigenome

  2020cites this paper
• The role of H3K9me2‐regulated base excision repair genes in the repair of DNA damage induced by arsenic in HaCaT cells and the effects of Ginkgo biloba extract intervention

  2020cites this paper
• Joint effects of genomic markers and urinary methylation capacity associated with inorganic arsenic metabolism on the occurrence of cancers among residents in arseniasis-endemic areas: A cohort subset with average fifteen-year follow-up

  2020cites this paper
• Environmental Arsenic Exposure and Human Health Risk

  2019cites this paper
• Impact of heavy metals with host cells: Special focus on nickel-mediated pathologies and novel interventional approaches.

  2019cites this paper
• Exposure to arsenic in utero is associated with various types of DNA damage and micronuclei in newborns: a birth cohort study

  2019cites this paper
• Risk assessment of low arsenic exposure using biomarkers of oxidative and genotoxic stress in a piscine model

  2019cites this paper
• Association between selenium, cadmium, and arsenic levels and genetic polymorphisms in DNA repair genes (XRCC5, XRCC6) in gastric cancerous and non-cancerous tissue.

  2019cites this paper
• Exposure to Arsenite in CD-1 Mice during Juvenile and Adult Stages: Effects on Intestinal Microbiota and Gut-Associated Immune Status

  2018cites this paper
• Environmental arsenic exposure: From genetic susceptibility to pathogenesis.

  2018cites this paper
• The role of molecular modelling strategies in validating the effects of chrysin on sodium arsenite-induced chromosomal and DNA damage

  2018cites this paper
• The Effect of Aqueous Extract of White Tea on the Levels of Antioxidant Enzymes of Rats\' Liver Tissue Exposed to Arsenic

  2018cites this paper
• Genotoxicity of 11 heavy metals detected as food contaminants in two human cell lines

  2018cites this paper
• Chronic Arsenic Toxicity and Cancer Corresponding

  2018cites this paper
• Arsenicosis in bladder pathology and schistosomiasis in Eggua, Nigeria

  2018cites this paper
• Dual effects of sulfasalazine on rat sperm characteristics, spermatogenesis, and steroidogenesis in two experimental models.

  2018cites this paper
• Quantitative assessment of lung and bladder cancer risk and oral exposure to inorganic arsenic: Meta-regression analyses of epidemiological data.

  2017cites this paper
• Molecular insight of arsenic-induced carcinogenesis and its prevention

  2017cites this paper
• Long-term exposure of immortalized keratinocytes to arsenic induces EMT, impairs differentiation in organotypic skin models and mimics aspects of human skin derangements

  2017cites this paper
• Cytotoxicity and genotoxicity effects of arsenic trioxide on SQ20B human laryngeal carcinoma cells.

  2017influential citation
• Effects of arsenic toxicity beyond epigenetic modifications

  2017cites this paper
• Oncogenomic disruptions in arsenic-induced carcinogenesis

  2017cites this paper
• Relationship between genotoxic damage and arsenic blood concentrations in individuals residing in an arsenic contaminated area in Morelos, Mexico

  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2015cites this paper
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  2015cites this paper
• Repair Activity Impaired by Arsenic: Recovery by Phytochemicals

  2015cites this paper
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• Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes.

  2014cites this paper
• Genotoxic and epigenetic mechanisms in arsenic carcinogenicity

  2014influential citation
• Epitenetic mechanisms of arsenic-induced transformation in human keratinocytes

  2014cites this paper
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• Arsenic Contamination: Unavoidable Natural Phenomenon or an Anthropogenic Crisis

  2013cites this paper
• Arsenic in drinking and lung cancer mortality in Taiwan

  2013cites this paper
• Reduction of arsenite-enhanced ultraviolet radiation-induced DNA damage by supplemental zinc.

  2013cites this paper
• Arsenic Exposure and Cancer Mortality in a US-Based Prospective Cohort: The Strong Heart Study

  2013cites this paper
• Arsenic-Induced Genotoxicity and Genetic Susceptibility to Arsenic-Related Pathologies

  2013influential citation
• Myocardial toxicity of acute promyelocytic leukaemia drug-arsenic trioxide.

  2013cites this paper
• Modeling the Effects of Dietary Arsenic and Nutrient Intake on Urinary Arsenic Biomarkers

  2012cites this paper
• The epigenetic lorax: gene-environment interactions in human health.

  2012cites this paper
• Hepatoprotective efficacy of curcumin against arsenic trioxide toxicity

  2012cites this paper
• Estudo comparativo da qualidade parasitológica e toxicológica entre hortaliças cultivadas com água de reuso e hortaliças comercializadas em Ribeirão Preto - SP.

  2011cites this paper
• Induction of Human Squamous Cell-Type Carcinomas by Arsenic

  2011cites this paper