{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:46:48Z","timestamp":1790794008650,"version":"4.1.0"},"reference-count":80,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T00:00:00Z","timestamp":1600732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ES000260"],"award-info":[{"award-number":["ES000260"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ES022935"],"award-info":[{"award-number":["ES022935"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ES023174"],"award-info":[{"award-number":["ES023174"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ES026138"],"award-info":[{"award-number":["ES026138"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Arsenic occurs naturally in the environment, and exists predominantly as inorganic arsenite (As (III) and arsenate As (V)). Arsenic contamination of drinking water has long been recognized as a major global health concern. Arsenic exposure causes changes in skin color and lesions, and more severe health conditions such as black foot disease as well as various cancers originating in the lungs, skin, and bladder. In order to efficiently metabolize and excrete arsenic, it is methylated to monomethylarsonic and dimethylarsinic acid. One single enzyme, arsenic methyltransferase (AS3MT) is responsible for generating both metabolites. AS3MT has been purified from several mammalian and nonmammalian species, and its mRNA sequences were determined from amino acid sequences. With the advent of genome technology, mRNA sequences of AS3MT have been predicted from many species throughout the animal kingdom. Horizontal gene transfer had been postulated for this gene through phylogenetic studies, which suggests the importance of this gene in appropriately handling arsenic exposures in various organisms. An altered ability to methylate arsenic is dependent on specific single nucleotide polymorphisms (SNPs) in AS3MT. Reduced AS3MT activity resulting in poor metabolism of iAs has been shown to reduce expression of the tumor suppressor gene, p16, which is a potential pathway in arsenic carcinogenesis. Arsenic is also known to induce oxidative stress in cells. However, the presence of antioxidant response elements (AREs) in the promoter sequences of AS3MT in several species does not correlate with the ability to methylate arsenic. ARE elements are known to bind NRF2 and induce antioxidant enzymes to combat oxidative stress. NRF2 may be partly responsible for the biotransformation of iAs and the generation of methylated arsenic species via AS3MT. In this article, arsenic metabolism, excretion, and toxicity, a discussion of the AS3MT gene and its evolutionary history, and DNA methylation resulting from arsenic exposure have been reviewed.<\/jats:p>","DOI":"10.3390\/biom10091351","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T02:56:43Z","timestamp":1600916203000},"page":"1351","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Arsenic Methyltransferase and Methylation of Inorganic Arsenic"],"prefix":"10.3390","volume":"10","author":[{"given":"Nirmal K.","family":"Roy","sequence":"first","affiliation":[{"name":"Department of Environmental Medicine, NYU School of Medicine, 341 East 25th Street, New York, NY 10010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine, NYU School of Medicine, 341 East 25th Street, New York, NY 10010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine, NYU School of Medicine, 341 East 25th Street, New York, NY 10010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1159\/000507805","article-title":"When Poisons Cure: The Case of Arsenic in Acute Promyelocytic Leukemia","volume":"64","author":"Gurnari","year":"2019","journal-title":"Chemotherapy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0016-7037(55)90042-9","article-title":"Geochemistry of arsenic","volume":"7","author":"Onishi","year":"1955","journal-title":"Geochimica et Cosmochimica Acta"},{"key":"ref_3","unstructured":"Chou, C.H., and Harper, C. (2007). Toxicological Profile for Arsenic."},{"key":"ref_4","unstructured":"WHO (2020, June 01). Arsenic\u2014World Health Organizaiton. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/arsenic."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/0043-1354(72)90052-8","article-title":"A review of the arsenic cycle in natural waters","volume":"6","author":"Ferguson","year":"1972","journal-title":"Water Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"253","DOI":"10.3961\/jpmph.14.036","article-title":"Environmental source of arsenic exposure","volume":"47","author":"Chung","year":"2014","journal-title":"J. Prev. Med. Public Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1136\/pmj.79.933.391","article-title":"Acute and chronic arsenic toxicity","volume":"79","author":"Ratnaike","year":"2003","journal-title":"Postgrad. Med. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.taap.2004.11.022","article-title":"Arsenic exposure, urinary arsenic speciation, and peripheral vascular disease in blackfoot disease-hyperendemic villages in Taiwan","volume":"206","author":"Tseng","year":"2005","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1177\/000331978904000606","article-title":"Blackfoot disease in Taiwan: A 30-year follow-up study","volume":"40","author":"Tseng","year":"1989","journal-title":"Angiology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S1470-2045(09)70134-2","article-title":"A review of human carcinogens\u2014Part C: Metals, arsenic, dusts, and fibres","volume":"10","author":"Straif","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhu, Y., and Costa, M. (2020). Metals and Molecular Carcinogenesis. Carcinogenesis.","DOI":"10.1093\/carcin\/bgaa076"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.taap.2006.12.033","article-title":"Further evidence against a direct genotoxic mode of action for arsenic-induced cancer","volume":"222","author":"Klein","year":"2007","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1093\/toxsci\/kfn104","article-title":"Decreased urinary beta-defensin-1 expression as a biomarker of response to arsenic","volume":"106","author":"Hegedus","year":"2008","journal-title":"Toxicol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ravenscroft, P., Brammer, H., and Richards, K. (2009). Arsenic Pollution: A global Synthesis, John Wiley & Sons.","DOI":"10.1002\/9781444308785"},{"key":"ref_15","first-page":"1093","article-title":"Contamination of drinking-water by arsenic in Bangladesh: A public health emergency","volume":"78","author":"Smith","year":"2000","journal-title":"Bull. World Health Organ."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1503\/cmaj.071456","article-title":"Arsenic threat reaching global dimensions","volume":"177","author":"Bagchi","year":"2007","journal-title":"CMAJ"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1289\/ehp.1205875","article-title":"The broad scope of health effects from chronic arsenic exposure: Update on a worldwide public health problem","volume":"121","author":"Naujokas","year":"2013","journal-title":"Environ. Health Perspect."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"207","DOI":"10.5001\/omj.2011.51","article-title":"Arsenic poisoning in bangladesh","volume":"26","author":"Uddin","year":"2011","journal-title":"Oman Med. J."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yu, W.H., Harvey, C.M., and Harvey, C.F. (2003). Arsenic in groundwater in Bangladesh: A geostatistical and epidemiological framework for evaluating health effects and potential remedies. Water Resour. Res., 39.","DOI":"10.1029\/2002WR001327"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/0926-6917(95)90066-7","article-title":"A unique metabolism of inorganic arsenic in native Andean women","volume":"293","author":"Vahter","year":"1995","journal-title":"Eur. J. Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.jes.2016.10.004","article-title":"Comparative cytotoxicity of fourteen trivalent and pentavalent arsenic species determined using real-time cell sensing","volume":"49","author":"Moe","year":"2016","journal-title":"J. Environ. Sci. (China)"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1006\/taap.2001.9258","article-title":"The cellular metabolism and systemic toxicity of arsenic","volume":"176","author":"Thomas","year":"2001","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_23","first-page":"396","article-title":"Biological methylation","volume":"35","author":"Challenger","year":"1947","journal-title":"Sci. Prog."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jtemb.2016.10.002","article-title":"Tissue-specific distributions of inorganic arsenic and its methylated metabolites, especially in cerebral cortex, cerebellum and hippocampus of mice after a single oral administration of arsenite","volume":"43","author":"Li","year":"2017","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1177\/003685049908200104","article-title":"Methylation of inorganic arsenic in different mammalian species and population groups","volume":"82","author":"Vahter","year":"1999","journal-title":"Sci. Prog."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s002040000134","article-title":"Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells","volume":"74","author":"Styblo","year":"2000","journal-title":"Arch. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/BF00405933","article-title":"Comparison of the urinary excretion of arsenic metabolites after a single oral dose of sodium arsenite, monomethylarsonate, or dimethylarsinate in man","volume":"48","author":"Buchet","year":"1981","journal-title":"Int. Arch. Occup. Environ. Health"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/BF00378431","article-title":"Urinary excretion of inorganic arsenic and its metabolites after repeated ingestion of sodium metaarsenite by volunteers","volume":"48","author":"Buchet","year":"1981","journal-title":"Int. Arch. Occup. Environ. Health"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7769","DOI":"10.1021\/cr300015c","article-title":"Arsenic binding to proteins","volume":"113","author":"Shen","year":"2013","journal-title":"Chem. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.taap.2010.04.013","article-title":"Severe systemic toxicity and urinary bladder cytotoxicity and regenerative hyperplasia induced by arsenite in arsenic (+3 oxidation state) methyltransferase knockout mice. A preliminary report","volume":"246","author":"Yokohira","year":"2010","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/toxsci\/kfs154","article-title":"Release of apoptotic cytochrome C from mitochondria by dimethylarsinous acid occurs through interaction with voltage-dependent anion channel in vitro","volume":"128","author":"Naranmandura","year":"2012","journal-title":"Toxicol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1039\/C4MT00119B","article-title":"Trivalent methylated arsenic metabolites induce apoptosis in human myeloid leukemic HL-60 cells through generation of reactive oxygen species","volume":"6","author":"Rehman","year":"2014","journal-title":"Metallomics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1021\/tx000251l","article-title":"Methylated trivalent arsenic species are genotoxic","volume":"14","author":"Mass","year":"2001","journal-title":"Chem. Res. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00204-013-1141-2","article-title":"Methylarsonous acid causes oxidative DNA damage in cells independent of the ability to biomethylate inorganic arsenic","volume":"88","author":"Tokar","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"A150","DOI":"10.1289\/ehp.124-A150","article-title":"Organoarsenic Drugs over Time: The Pharmacokinetics of Roxarsone in Chicken Meat","volume":"124","author":"Konkel","year":"2016","journal-title":"Environ. Health Perspect."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10795","DOI":"10.1074\/jbc.M110246200","article-title":"A novel S-adenosyl-L-methionine:arsenic(III) methyltransferase from rat liver cytosol","volume":"277","author":"Lin","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.taap.2004.12.002","article-title":"Arsenic (+3 oxidation state) methyltransferase and the inorganic arsenic methylation phenotype","volume":"204","author":"Li","year":"2005","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1745-6150-9-20","article-title":"A new rhesus macaque assembly and annotation for next-generation sequencing analyses","volume":"9","author":"Zimin","year":"2014","journal-title":"Biol. Direct"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.taap.2003.10.020","article-title":"Elucidating the pathway for arsenic methylation","volume":"198","author":"Thomas","year":"2004","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1021\/tx00050a006","article-title":"Enzymatic methylation of arsenic compounds: Assay, partial purification, and properties of arsenite methyltransferase and monomethylarsonic acid methyltransferase of rabbit liver","volume":"8","author":"Zakharyan","year":"1995","journal-title":"Chem. Res. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1146\/annurev.pharmtox.37.1.397","article-title":"Enzymatic methylation of arsenic species and other new approaches to arsenic toxicity","volume":"37","author":"Aposhian","year":"1997","journal-title":"Annu. Rev. Pharm. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1093\/toxsci\/kfr184","article-title":"Arsenic exposure and toxicology: A historical perspective","volume":"123","author":"Hughes","year":"2011","journal-title":"Toxicol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1006\/taap.1999.8687","article-title":"Enzymatic methylation of arsenic compounds. VII. Monomethylarsonous acid (MMAIII) is the substrate for MMA methyltransferase of rabbit liver and human hepatocytes","volume":"158","author":"Zakharyan","year":"1999","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_44","unstructured":"Zhu, Y., Guo, H., Bhattacharya, P., Ahmad, A., Bundschuh, J., and Naidu, R. (2019). Mechanism of as(III) S-adenosylmethionine methyltransferases and the consequences of human polymorphisms in hAS3MT. Environmental Arsenic in a Changing World, CRC Press. [1st ed.]."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5213","DOI":"10.1073\/pnas.0900238106","article-title":"Biotransformation of arsenic by a Yellowstone thermoacidophilic eukaryotic alga","volume":"106","author":"Qin","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1021\/bi201500c","article-title":"Identification of catalytic residues in the as(III) S-adenosylmethionine methyltransferase","volume":"51","author":"Marapakala","year":"2012","journal-title":"Biochemistry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5476","DOI":"10.1021\/bi3004632","article-title":"Structure of an As(III) S-adenosylmethionine methyltransferase: Insights into the mechanism of arsenic biotransformation","volume":"51","author":"Ajees","year":"2012","journal-title":"Biochemistry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1021\/tx500313k","article-title":"Pathway of human AS3MT arsenic methylation","volume":"27","author":"Dheeman","year":"2014","journal-title":"Chem. Res. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Palmgren, M., Engstr\u00f6m, K., Hallstr\u00f6m, B.M., Wahlberg, K., S\u00f8ndergaard, D.A., S\u00e4ll, T., and Broberg, K. (2017). AS3MT-mediated tolerance to arsenic evolved by multiple independent horizontal gene transfers from bacteria to eukaryotes. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0175422"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.taap.2012.07.024","article-title":"Methylation of arsenic by recombinant human wild-type arsenic (+3 oxidation state) methyltransferase and its methionine 287 threonine (M287T) polymorph: Role of glutathione","volume":"264","author":"Ding","year":"2012","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1097\/FPC.0b013e3282f7f46b","article-title":"High arsenic metabolic efficiency in AS3MT287Thr allele carriers","volume":"18","author":"Hernandez","year":"2008","journal-title":"Pharm. Genom."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1021\/acs.chemrestox.7b00113","article-title":"Nonsynonymous Polymorphisms in the Human AS3MT Arsenic Methylation Gene: Implications for Arsenic Toxicity","volume":"30","author":"Li","year":"2017","journal-title":"Chem. Res. Toxicol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1177\/0748233708093355","article-title":"Differential oxidative stress and DNA damage in rat brain regions and blood following chronic arsenic exposure","volume":"24","author":"Mishra","year":"2008","journal-title":"Toxicol. Ind. Health"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Mathers, J., Fraser, J.A., McMahon, M., Saunders, R.D., Hayes, J.D., and McLellan, L.I. (2004). Antioxidant and cytoprotective responses to redox stress. Biochem. Soc. Symp., 157\u2013176.","DOI":"10.1042\/bss0710157"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1089\/ars.2005.7.385","article-title":"Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation","volume":"7","author":"Kobayashi","year":"2005","journal-title":"Antioxid. Redox Signal."},{"key":"ref_56","unstructured":"Muriel, P. (2017). Nrf2: A Key Regulator of Redox Signaling in Liver Diseases. Liver Pathophysiology, Academic Press."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5361","DOI":"10.1073\/pnas.94.10.5361","article-title":"Functional antioxidant responsive elements","volume":"94","author":"Wasserman","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7130","DOI":"10.1128\/MCB.24.16.7130-7139.2004","article-title":"Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2","volume":"24","author":"Kobayashi","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Chatterjee, N., Tian, M., Spirohn, K., Boutros, M., and Bohmann, D. (2016). Keap1-Independent Regulation of Nrf2 Activity by Protein Acetylation and a BET Bromodomain Protein. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006072"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"23620","DOI":"10.1074\/jbc.M604120200","article-title":"Arsenic induces NAD(P)H-quinone oxidoreductase I by disrupting the Nrf2 x Keap1 x Cul3 complex and recruiting Nrf2 x Maf to the antioxidant response element enhancer","volume":"281","author":"He","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.taap.2008.03.003","article-title":"Activation of Nrf2 by arsenite and monomethylarsonous acid is independent of Keap1-C151: Enhanced Keap1-Cul3 interaction","volume":"230","author":"Wang","year":"2008","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"27251","DOI":"10.1074\/jbc.M602746200","article-title":"Nrf2 possesses a redox-sensitive nuclear exporting signal in the Neh5 transactivation domain","volume":"281","author":"Li","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.jtbi.2012.09.019","article-title":"A semi-mechanistic integrated toxicokinetic-toxicodynamic (TK\/TD) model for arsenic(III) in hepatocytes","volume":"317","author":"Stamatelos","year":"2013","journal-title":"J. Theor. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.freeradbiomed.2014.10.575","article-title":"Regulation of iNOS function and cellular redox state by macrophage Gch1 reveals specific requirements for tetrahydrobiopterin in NRF2 activation","volume":"79","author":"McNeill","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_65","unstructured":"(2020, June 01). Clustal Omega. Available online: https:\/\/www.ebi.ac.uk\/Tools\/msa\/clustalo\/."},{"key":"ref_66","unstructured":"(2020, June 01). Simple Phylogeny. Available online: https:\/\/www.ebi.ac.uk\/Tools\/phylogeny\/simple_phylogeny\/."},{"key":"ref_67","first-page":"3","article-title":"Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals","volume":"232","author":"Thomas","year":"2007","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1271\/bbb.100751","article-title":"Rapid biotransformation of arsenate into oxo-arsenosugars by a freshwater unicellular green alga, Chlamydomonas reinhardtii","volume":"75","author":"Miyashita","year":"2011","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1289\/ehp.1002114","article-title":"An emerging role for epigenetic dysregulation in arsenic toxicity and carcinogenesis","volume":"119","author":"Ren","year":"2011","journal-title":"Environ. Health Perspect."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.toxlet.2010.10.015","article-title":"Effects of MEK and DNMT inhibitors on arsenic-treated human uroepithelial cells in relation to Cyclin-D1 and p16","volume":"200","author":"Huang","year":"2011","journal-title":"Toxicol. Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1093\/carcin\/bgm228","article-title":"Carcinogenesis and microsatellite instability: The interrelationship between genetics and epigenetics","volume":"29","author":"Imai","year":"2008","journal-title":"Carcinogenesis"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1039\/c2mt20120h","article-title":"Environmental arsenic exposure and DNA methylation of the tumor suppressor gene p16 and the DNA repair gene MLH1: Effect of arsenic metabolism and genotype","volume":"4","author":"Hossain","year":"2012","journal-title":"Metallomics"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1289\/ehp.1002471","article-title":"Polymorphisms in arsenic(+III oxidation state) methyltransferase (AS3MT) predict gene expression of AS3MT as well as arsenic metabolism","volume":"119","author":"Engstrom","year":"2011","journal-title":"Environ. Health Perspect."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1289\/ehp.9734","article-title":"Genetic polymorphisms influencing arsenic metabolism: Evidence from Argentina","volume":"115","author":"Broberg","year":"2007","journal-title":"Environ. Health Perspect."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Engstrom, K.S., Hossain, M.B., Lauss, M., Ahmed, S., Raqib, R., Vahter, M., and Broberg, K. (2013). Efficient arsenic metabolism\u2014The AS3MT haplotype is associated with DNA methylation and expression of multiple genes around AS3MT. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053732"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"7364","DOI":"10.1074\/jbc.M512227200","article-title":"Human arsenic methyltransferase (AS3MT) pharmacogenetics: Gene resequencing and functional genomics studies","volume":"281","author":"Wood","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/s41437-019-0285-0","article-title":"Recent population genomic insights into the genetic basis of arsenic tolerance in humans: The difficulties of identifying positively selected loci in strongly bottlenecked populations","volume":"124","author":"Apata","year":"2020","journal-title":"Heredity (Edinb.)"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/ajpa.23193","article-title":"Human adaptation to arsenic in Andean populations of the Atacama Desert","volume":"163","author":"Apata","year":"2017","journal-title":"Am. J. Phys. Anthr."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/evan.21720","article-title":"Living in poisoning environments: Invisible risks and human adaptation","volume":"27","author":"Arriaza","year":"2018","journal-title":"Evol. Anthr."},{"key":"ref_80","first-page":"255","article-title":"Arseniasis as an environmental hypothetical explanation for the origin of the oldest artificial mummification practice in the world","volume":"37","author":"Ariazza","year":"2005","journal-title":"Chungara Revista de Antropo\u013aogia Chilena"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/9\/1351\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:12:24Z","timestamp":1760177544000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/9\/1351"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,22]]},"references-count":80,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["biom10091351"],"URL":"https:\/\/doi.org\/10.3390\/biom10091351","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,22]]}}}