Abstract
Arsenic is a well-known environmental carcinogen and chronic exposure to arsenic through drinking water has been reported to cause skin, bladder and lung cancers, with arsenic metabolites being implicated in the pathogenesis. In contrast, arsenic trioxide (As2O3) is an effective therapeutic agent for the treatment of acute promyelocytic leukemia, in which the binding of arsenite (iAsIII) to promyelocytic leukemia (PML) protein is the proposed initial step. These findings on the two-edged sword characteristics of arsenic suggest that after entry into cells, arsenic reaches the nucleus and triggers various nuclear events. Arsenic is reduced, conjugated with glutathione, and methylated in the cytosol. These biotransformations, including the production of reactive metabolic intermediates, appear to determine the intracellular dynamics, target organs, and biological functions of arsenic.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Allred AL, Hensley AL (1961) Electronegativities of nitrogen, phosphorus, arsenic, antimony and bismuth. J Inorg Nucl Chem 17(1–2):43–54. https://doi.org/10.1016/0022-1902(61)80184-X
Andreae MO (1978) Distribution and speciation of arsenic in natural-waters and some marine-algae. Deep-Sea Res 25(4):391–402. https://doi.org/10.1016/0146-6291(78)90565-9
Andrewes P, Kitchin KT, Wallace K (2003) Dimethylarsine and trimethylarsine are potent genotoxins in vitro. Chem Res Toxicol 16:994–1003
Aposhian HV (1997) Enzymatic methylation of arsenic species and other new approaches to arsenic toxicity. Annu Rev Pharmacol Toxicol 37:397–419
Azeem M, Brownste M, Gillespi RJ (1969) An investigation of structures of adducts of Sf4 with Bf3 Pf5 Asf5 and Sbf5 in solid state and in solution in Hf. Canad J Chem 47(22):4159. https://doi.org/10.1139/v69-689
Banani S, Lee H, Hyman A, Rosen M (2017) Biomolecular condensates: organizers of cellular biochemistry. Nat Rev Mol Cell Biol 18(5):285–298. https://doi.org/10.1038/nrm.2017.7
Bellomo G, Palladini G, Vairetti M (1997) Intranuclear distribution, function and fate of glutathione and glutathione-S-conjugate in living rat hepatocytes studied by fluorescence microscopy. Microsc Res Tech 36(4):243–252
Bentley R, Chasteen T (2002) Microbial methylation of metalloids: arsenic, antimony, and bismuth. Microbiol Mol Biol Rev 66(2):250–271. https://doi.org/10.1128/mmbr.66.2.250-271.2002
Bird ML, Challenger F, Charlton PT, Smith JO (1948) Studies on biological methylation 11. The action of moulds on inorganic and organic compounds of arsenic. Biochem J 43(1):78–83
Bluemlein K, Raab A, Feldmann J (2009) Stability of arsenic peptides in plant extracts: off-line versus on-line parallel elemental and molecular mass spectrometric detection for liquid chromatographic separation. Anal Bioanal Chem 393(1):357–366. https://doi.org/10.1007/s00216-008-2395-z
Bozack A, Hall M, Liu X et al (2019) Folic acid supplementation enhances arsenic methylation: results from a folic acid and creatine supplementation randomized controlled trial in Bangladesh. Am J Clin Nutr 109(2):380–391. https://doi.org/10.1093/ajcn/nqy148
Burns FJ, Uddin AN, Wu F, Nadas A, Rossman TG (2004) Arsenic-induced enhancement of ultraviolet radiation carcinogenesis in mouse skin: a dose-response study. Environ Health Perspect 112(5):599–603
Calatayud M, Gimeno J, Velez D, Devesa V, Montoro R (2010) Characterization of the intestinal absorption of arsenate, monomethylarsonic acid, and dimethylarsinic acid using the Caco-2 cell line. Chem Res Toxicol 23(3):547–556
Carew MW, Leslie EM (2010) Selenium-dependent and -independent transport of arsenic by the human multidrug resistance protein 2 (MRP2/ABCC2): implications for the mutual detoxification of arsenic and selenium. Carcinogenesis 31(8):1450–1455
Challenger F (1945) Biological methylation. Chem Rev 36:315–361
Chen B, Arnold L, Cohen S, Thomas D, Le X (2011) Mouse arsenic (+3 oxidation state) methyltransferase genotype affects metabolism and tissue dosimetry of arsenicals after arsenite administration in drinking water. Toxicol Sci 124(2):320–326. https://doi.org/10.1093/toxsci/kfr246
Chen J, Qin J, Zhu YG, de Lorenzo V, Rosen BP (2013) Engineering the soil bacterium pseudomonas putida for arsenic methylation. Appl Environ Microb 79(14):4493–4495. https://doi.org/10.1128/Aem.01133-13
Chi L, Xue J, Tu P, Lai Y, Ru H, Lu K (2019) Gut microbiome disruption altered the biotransformation and liver toxicity of arsenic in mice. Arch Toxicol 93(1):25–35. https://doi.org/10.1007/s00204-018-2332-7
Coryell M, McAlpine M, Pinkham N, McDermott T, Walk S (2018) The gut microbiome is required for full protection against acute arsenic toxicity in mouse models. Nat Commun 9(1):5424. https://doi.org/10.1038/s41467-018-07803-9
Csanaky I, Gregus Z (2001) Effect of phosphate transporter and methylation inhibitor drugs on the disposition of arsenate and arsenite in rats. Toxicol Sci 63(1):29–36
Cullen WR, McBride BC, Pickett AW, Reglinski J (1984) The wood preservative chromated copper arsenate is a substrate for trimethylarsine biosynthesis. Appl Environ Microbiol 47(2):443–444
Cullen WR, McBride BC, Manji H, Pickett AW, Reglinski J (1989) The metabolism of methylarsine oxide and sulfide. Appl Organomet Chem 3:71–78
de The H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A (1991) The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell 66(4):675–684
de The H, Le Bras M, Lallemand-Breitenbach V (2012) The cell biology of disease: acute promyelocytic leukemia, arsenic, and PML bodies. J Cell Biol 198(1):11–21. https://doi.org/10.1083/jcb.201112044
Del Razo LM, Styblo M, Cullen WR, Thomas DJ (2001) Determination of trivalent methylated arsenicals in biological matirices. Toxicol Appl Pharmacol 174:282–293
Dheeman DS, Packianathan C, Pillai JK, Rosen BP (2014) Pathway of human AS3MT arsenic methylation. Chem Res Toxicol 27(11):1979–1989. https://doi.org/10.1021/tx500313k
Dopp E, Hartmann LM, von Recklinghausen U et al (2005) Forced uptake of trivalent and pentavalent methylated and inorganic arsenic and its cyto-/genotoxicity in fibroblasts and hepatoma cells. Toxicol Sci 87(1):46–56
Drobna Z, Naranmandura H, Kubachka KM et al (2009) Disruption of the arsenic (+3 Oxidation State) methyltransferase gene in the mouse alters the phenotype for methylation of arsenic and affects distribution and retention of orally administered arsenate. Chem Res Toxicol 22(10):1713–1720
Eguchi N, Kuroda K, Endo G (1997) Metabolites of arsenic induced tetraploids and mitotic arrest in cultured cells. Arch Environ Contam Toxicol 32(2):141–145
Elias M, Wellner A, Goldin-Azulay K et al (2012) The molecular basis of phosphate discrimination in arsenate-rich environments. Nature 491(7422):134–137. https://doi.org/10.1038/nature11517
Enami S, Hoffmann MR, Colussi AJ (2015) OH-Radical Specific addition to glutathione S-Atom at the air-water interface: relevance to the redox balance of the lung epithelial lining fluid. J Phys Chem Lett 6(19):3935–3943. https://doi.org/10.1021/acs.jpclett.5b01819
Erb T, Kiefer P, Hattendorf B, Gunther D, Vorholt J (2012) GFAJ-1 is an arsenate-resistant, phosphate-dependent organism. Science 337(6093):467–470. https://doi.org/10.1126/science.1218455
Fomenko DE, Xing W, Adair BM, Thomas DJ, Gladyshev VN (2007) High-throughput identification of catalytic redox-active cysteine residues. Science 315(5810):387–389. https://doi.org/10.1126/science.1133114
Forman H, Davies M, Kramer A et al (2017) Protein cysteine oxidation in redox signaling: caveats on sulfenic acid detection and quantification. Arch Biochem Biophys 617:26–37. https://doi.org/10.1016/j.abb.2016.09.013
Gadd G (2019) Arsenic toxicity: an arsenic-hyperaccumulating fern uses a bacterial-like tolerance mechanism. Curr Biol 29(12):R580–R582. https://doi.org/10.1016/j.cub.2019.05.003
Garcia-Salgado S, Raber G, Raml R, Magnes C, Francesconi KA (2012) Arsenosugar phospholipids and arsenic hydrocarbons in two species of brown macroalgae. Environ Chem 9(1):63–66. https://doi.org/10.1071/EN11164
Garnier N, Redstone GG, Dahabieh MS et al (2014) The novel arsenical darinaparsin is transported by cystine importing systems. Mol Pharmacol 85(4):576–585. https://doi.org/10.1124/mol.113.089433
Gebel T (1997) Arsenic and antimony: comparative approach on mechanistic toxicology. Chem Biol Interact 107(3):131–144. https://doi.org/10.1016/s0009-2797(97)00087-2
Goering PL, Aposhian HV, Mass MJ, Cebrian M, Beck BD, Waalkes MP (1999) The enigma of arsenic carcinogenesis: role of metabolism. Toxicol Sci 49(1):5–14
Gregus Z, Nemeti B (2002) Purine nucleoside phosphorylase as a cytosolic arsenate reductase. Toxicol Sci 70:13–19
Gregus Z, Gyurasics A, Koszorus L (1998) Interactions between selenium and group va-metalloids (arsenic, antimony and bismuth) in the biliary excretion. Environ Toxicol Pharmacol 5(2):89–99. https://doi.org/10.1016/s1382-6689(97)10008-4
Guimaraes LHS, Segura FR, Tonani L et al (2019) Arsenic volatilization by Aspergillus sp. and Penicillium sp. isolated from rice rhizosphere as a promising eco-safe tool for arsenic mitigation. J Environ Manag 237:170–179. https://doi.org/10.1016/j.jenvman.2019.02.060
Gupta V, Carroll K (1840) Carroll K (2014) Sulfenic acid chemistry, detection and cellular lifetime. Biochim Biophys Acta 2:847–875. https://doi.org/10.1016/j.bbagen.2013.05.040
Han MJ, Meng X, Lippincott L (2007) Determination of configuration of arsenite-glutathione complexes using ECSTM. Toxicol Lett 175(1–3):57–63. https://doi.org/10.1016/j.toxlet.2007.09.009
Hasegawa H, Papry R, Ikeda E et al (2019) Freshwater phytoplankton: biotransformation of inorganic arsenic to methylarsenic and organoarsenic. Sci Rep 9(1):12074. https://doi.org/10.1038/s41598-019-48477-7
Hayakawa T, Kobayashi Y, Cui X, Hirano S (2005) A new metabolic pathway of arsenite: arsenic-glutathione complexes are substrates for human arsenic methyltransferase Cyt19. Arch Toxicol 79(4):183–191. https://doi.org/10.1007/s00204-004-0620-x
He X, Ma Q (2009) Induction of metallothionein I by arsenic via metal-activated transcription factor 1: critical role of C-terminal cysteine residues in arsenic sensing. J Biol Chem 284(19):12609–12621. https://doi.org/10.1074/jbc.M901204200
He X, Chen MG, Lin GX, Ma Q (2006) 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. J Biol Chem 281(33):23620–23631
Healy SM, Casarez EA, Ayala-Fierro F, Aposhian H (1998) Enzymatic methylation of arsenic compounds V. Arsenite methyltransferase activity in tissues of mice. Toxicol Appl Pharmacol 148(1):65–70
Healy SM, Wildfang E, Zakharyan RA, Aposhian HV (1999) Diversity of inorganic arsenite biotransformation. Biol Trace Elem Res 68(3):249–266
Hester S, Drobna Z, Andrews D et al (2009) Expression of AS3MT alters transcriptional profiles in human urothelial cells exposed to arsenite. Hum Exp Toxicol 28(1):49–61. https://doi.org/10.1177/0960327109102368
Hirano S, Kobayashi Y (2006) Cytotoxic effects of S-(dimethylarsino)-glutathione: a putative intermediate metabolite of inorganic arsenicals. Toxicology 227(1–2):45–52. https://doi.org/10.1016/j.tox.2006.07.009
Hirano S, Cui X, Li S et al (2003) Difference in uptake and toxicity of trivalent and pentavalent inorganic arsenic in rat heart microvessel endothelial cells. Arch Toxicol 77(6):305–312. https://doi.org/10.1007/s00204-003-0447-x
Hirano S, Kobayashi Y, Cui X, Kanno S, Hayakawa T, Shraim A (2004) The accumulation and toxicity of methylated arsenicals in endothelial cells: important roles of thiol compounds. Toxicol Appl Pharmacol 198(3):458–467. https://doi.org/10.1016/j.taap.2003.10.023
Hirano S, Watanabe T, Kobayashi Y (2013) Effects of arsenic on modification of promyelocytic leukemia (PML): PML responds to low levels of arsenite. Toxicol Appl Pharmacol 273(3):590–599. https://doi.org/10.1016/j.taap.2013.10.004
Hirano S, Tadano M, Kobayashi Y, Udagawa O, Kato A (2015) Solubility shift and sumoylaltion of promyelocytic leukemia (PML) protein in response to arsenic(III) and fate of the SUMOylated PML. Toxicol Appl Pharmacol 287(3):191–201. https://doi.org/10.1016/j.taap.2015.05.018
Hirano S, Udagawa O, Kobayashi Y, Kato A (2018) Solubility changes of promyelocytic leukemia (PML) and SUMO monomers and dynamics of PML nuclear body proteins in arsenite-treated cells. Toxicol Appl Pharmacol 360:150–159. https://doi.org/10.1016/j.taap.2018.10.001
Hosein P, Craig M, Tallman M et al (2012) A multicenter phase II study of darinaparsin in relapsed or refractory Hodgkin's and non-Hodgkin's lymphoma. Am J Hematol 87(1):111–114. https://doi.org/10.1002/ajh.22232
Howe C, Gamble M (2016) Influence of arsenic on global levels of histone posttranslational modifications: a review of the literature and challenges in the field. Curr Environ Health Rep 3(3):225–237. https://doi.org/10.1007/s40572-016-0104-1
Hughes MF, Edwards BC, Herbin-Davis KM, Saunders J, Styblo M, Thomas DJ (2010) Arsenic (+3 oxidation state) methyltransferase genotype affects steady-state distribution and clearance of arsenic in arsenate-treated mice. Toxicol Appl Pharmacol. https://doi.org/10.1016/j.taap.2010.09.017
IARC (2012) Arsenic, metals, fibres, and dusts. IARC Monogr Eval Carcinog Risks Hum 100(Pt C):11–465
Ilina Y, Sloma E, Maciaszczyk-Dziubinska E et al (2008) Characterization of the DNA-binding motif of the arsenic-responsive transcription factor Yap8p. Biochem J 415(3):467–475. https://doi.org/10.1042/BJ20080713
IPCS (2001) Arsenic and arsenic compounds, vol 224. World Health Organization, Geneva
Ito K, Bernardi R, Morotti A et al (2008) PML targeting eradicates quiescent leukaemia-initiating cells. Nature 453(7198):1072–1078. https://doi.org/10.1038/nature07016
Jiang J, Tam L, Wang P, Wang Y (2018) Arsenite targets the ring finger domain of Rbx1 E3 ubiquitin ligase to inhibit proteasome-mediated degradation of Nrf2. Chem Res Toxicol 31(5):380–387. https://doi.org/10.1021/acs.chemrestox.8b00062
Kakizuka A, Miller WH Jr, Umesono K et al (1991) Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor. PML Cell 66(4):663–674
Kala SV, Neely MW, Kala G et al (2000) The MRP2/cMOAT transporter and arsenic-glutathione complex formation are required for biliary excretion of arsenic. J Biol Chem 275(43):33404–33408
Kanaki K, Pergantis SA (2008) Development of mass spectrometric methods for detecting arsenic-glutathione complexes. J Am Soc Mass Spectr 19(10):1559–1567
Kato K, Yamanaka K, Hasegawa A, Okada S (2003) Active arsenic species produced by GSH-dependent reduction of dimethylarsinic acid cause micronuclei formation in peripheral reticulocytes of mice. Mutat Res 539(1–2):55–63
Kato A, Kobayashi Y, Udagawa O, Hirano S (2017) Pharmacodynamics of S-dimethylarsino-glutathione, a putative metabolic intermediate of inorganic arsenic, in mice. Biochem Pharmacol 126:79–86. https://doi.org/10.1016/j.bcp.2016.11.020
Kettenhofen N, Wood M (2010) Formation, reactivity, and detection of protein sulfenic acids. Chem Res Toxicol 23(11):1633–1646. https://doi.org/10.1021/tx100237w
Kitchin KT, Wallace K (2005) Arsenite binding to synthetic peptides based on the Zn finger region and the estrogen binding region of the human estrogen receptor-alpha. Toxicol Appl Pharmacol 206(1):66–72
Kitchin KT, Wallace K (2006a) Arsenite binding to synthetic peptides: the effect of increasing length between two cysteines. J Biochem Mol Toxicol 20(1):35–38
Kitchin KT, Wallace K (2006b) Dissociation of arsenite-peptide complexes: triphasic nature, rate constants, half-lives, and biological importance. J Biochem Mol Toxicol 20(1):48–56
Kobayashi Y, Hirano S (2008) Effects of endogenous hydrogen peroxide and glutathione on the stability of arsenic metabolites in rat bile. Toxicol Appl Pharmacol 232(1):33–40. https://doi.org/10.1016/j.taap.2008.06.003
Kobayashi Y, Hirano S (2013) The role of glutathione in the metabolism of diphenylarsinic acid in rats. Metallomics 5(5):469–478. https://doi.org/10.1039/c2mt20228j
Kobayashi Y, Cui X, Hirano S (2005) Stability of arsenic metabolites, arsenic triglutathione [As(GS)3] and methylarsenic diglutathione [CH3As(GS)2], in rat bile. Toxicology 211(1–2):115–123. https://doi.org/10.1016/j.tox.2005.03.001
Lallemand-Breitenbach V, Zhu J, Puvion F et al (2001) Role of promyelocytic leukemia (PML) sumolation in nuclear body formation, 11S proteasome recruitment, and As2O3-induced PML or PML/retinoic acid receptor alpha degradation. J Exp Med 193(12):1361–1371
Li JL, Sun YQ, Zhang X et al (2018) A methyltransferase gene from arbuscular mycorrhizal fungi involved in arsenic methylation and volatilization. Chemosphere 209:392–400. https://doi.org/10.1016/j.chemosphere.2018.06.092
Lin S, Shi Q, Nix FB et al (2002) A novel S-adenosyl-L-methionine: arsenic (III) methyltransferase from rat liver cytosol. J Biol Chem 277:10795–10803
Lindberg A, Rahman M, Persson L, Vahter M (2008) The risk of arsenic induced skin lesions in Bangladeshi men and women is affected by arsenic metabolism and the age at first exposure. Toxicol Appl Pharmacol 230(1):9–16. https://doi.org/10.1016/j.taap.2008.02.001
Lu M, Wang H, Li XF et al (2004) Evidence of hemoglobin binding to arsenic as a basis for the accumulation of arsenic in rat blood. Chem Res Toxicol 17(12):1733–1742
Lu M, Wang H, Wang Z, Li X, Le X (2008) Identification of reactive cysteines in a protein using arsenic labeling and collision-induced dissociation tandem mass spectrometry. J Proteome Res 7(8):3080–3090. https://doi.org/10.1021/pr700662y
Lu K, Cable PH, Abo RP et al (2013) Gut microbiome perturbations induced by bacterial infection affect arsenic biotransformation. Chem Res Toxicol 26(12):1893–1903. https://doi.org/10.1021/tx4002868
Maciaszczyk-Dziubinska E, Migdal I, Migocka M, Bocer T, Wysocki R (2010) The yeast aquaglyceroporin Fps1p is a bidirectional arsenite channel. FEBS Lett 584(4):726–732. https://doi.org/10.1016/j.febslet.2009.12.027
Maciaszczyk-Dziubinska E, Wawrzycka D, Wysocki R (2012) Arsenic and antimony transporters in eukaryotes. Int J Mol Sci 13(3):3527–3548. https://doi.org/10.3390/ijms13033527
Maroui M, Kheddache-Atmane S, El AF, Dianoux L, Aubry M, Chelbi-Alix M (2012) Requirement of PML SUMO interacting motif for RNF4- or arsenic trioxide-induced degradation of nuclear PML isoforms. PLoS ONE 7(9):e44949. https://doi.org/10.1371/journal.pone.0044949
Marshall G, Ferreccio C, Yuan Y et al (2007) Fifty-year study of lung and bladder cancer mortality in Chile related to arsenic in drinking water. J Natl Cancer Inst 99(12):920–928. https://doi.org/10.1093/jnci/djm004
Mass MJ, Tennant A, Roop BC et al (2001) Methylated trivalent arsenic species are genotoxic. Chem Res Toxicol 14(4):355–361
Meyer S, Matissek M, Muller SM et al (2014) In vitro toxicological characterisation of three arsenic-containing hydrocarbons. Metallomics 6(5):1023–1033. https://doi.org/10.1039/c4mt00061g
Mizoi M, Takabayashi F, Nakano M et al (2005) The role of trivalent dimethylated arsenic in dimethylarsinic acid-promoted skin and lung tumorigenesis in mice: tumor-promoting action through the induction of oxidative stress. Toxicol Lett 158(2):87–94. https://doi.org/10.1016/j.toxlet.2005.03.009
Mizumura A, Watanabe T, Kobayashi Y, Hirano S (2010) Identification of arsenite-and arsenic diglutathione-binding proteins in human hepatocarcinoma cells. Toxicol Appl Pharmacol 242(2):119–125. https://doi.org/10.1016/j.taap.2009.10.013
Mukhopadhyay R, Dey S, Xu N et al (1996) Trypanothione overproduction and resistance to antimonials and arsenicals in Leishmania. Proc Natl Acad Sci USA 93(19):10383–10387. https://doi.org/10.1073/pnas.93.19.10383
Mukhopadhyay R, Rosen B, Phung L, Silver S (2002) Microbial arsenic: from geocycles to genes and enzymes. FEMS Microbiol Rev 26(3):311–325. https://doi.org/10.1111/j.1574-6976.2002.tb00617.x
Muller S, Miller WH Jr, Dejean A (1998) Trivalent antimonials induce degradation of the PML-RAR oncoprotein and reorganization of the promyelocytic leukemia nuclear bodies in acute promyelocytic leukemia NB4 cells. Blood 92(11):4308–4316
Munro KL, Mariana A, Klavins AI et al (2008) Microprobe XRF mapping and XAS investigations of the intracellular metabolism of arsenic for understanding arsenic-induced toxicity. Chem Res Toxicol 21(9):1760–1769. https://doi.org/10.1021/tx800128d
Nakamura K, Yoshio H, Ling P, Yamauchi H (2009) Methyl transfer from a hydrophobic vitamin B-12 derivative to arsenic trioxide. J Organomet Chem 694(6):916–921. https://doi.org/10.1016/j.jorganchem.2008.12.002
Naranmandura H, Suzuki N, Suzuki KT (2006) Trivalent arsenicals are bound to proteins during reductive methylation. Chem Res Toxicol 19(8):1010–1018
Naranmandura H, Suzuki N, Iwata K, Hirano S, Suzuki KT (2007) Arsenic metabolism and thioarsenicals in hamsters and rats. Chem Res Toxicol 20(4):616–624. https://doi.org/10.1021/tx700038x
Neil B, Carpenter Y, Conrad E, Saunders CDL (2010) The chemistry of arsenic, antimony and bismuth. Wiley
Nemeti B, Gregus Z (2002a) Mitochondria work as reactors in reducing arsenate to arsenite. Toxicol Appl Pharmacol 182(3):208–218
Nemeti B, Gregus Z (2002b) Reduction of arsenate to arsenite in hepatic cytosol. Toxicol Sci 70:4–12
Nemeti B, Gregus Z (2013) Reduction of dimethylarsinic acid to the highly toxic dimethylarsinous acid by rats and rat liver cytosol. Chem Res Toxicol 26(3):432–443. https://doi.org/10.1021/tx300505v
Nemeti B, Csanaky I, Gregus Z (2003) Arsenate reduction in human erythrocytes and rats-testing the role of purine nucleoside phosphorylase. Toxicol Sci 74(1):22–31
Nielson K, Atkin C, Winge D (1985) Distinct metal-binding configurations in metallothionein. J Biol Chem 260(9):5342–5350
Nino S, Morales-Martinez A, Chi-Ahumada E et al (2019) Arsenic exposure contributes to the bioenergetic damage in an alzheimer's disease model. ACS Chem Neurosci 10(1):323–336. https://doi.org/10.1021/acschemneuro.8b00278
Ochi T, Kaise T, Oya-Ohta Y (1994) Glutathione plays different roles in the induction of the cytotoxic effects of inorganic and organic arsenic compounds in cultured BALB/c 3T3 cells. Experientia 50(2):115–120. https://doi.org/10.1007/bf01984946
Pakulska D, Czerczak S (2006) Hazardous effects of arsine: a short review. Int J Occup Med Environ Health 19(1):36–44. https://doi.org/10.2478/v10001-006-0003-z
Perry MR, Wyllie S, Raab A, Feldmann J, Fairlamb AH (2013) Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis. Proc Natl Acad Sci USA 110(49):19932–19937. https://doi.org/10.1073/pnas.1311535110
Piatek K, Schwerdtle T, Hartwig A, Bal W (2008) Monomethylarsonous acid destroys a tetrathiolate zinc finger much more efficiently than inorganic arsenite: mechanistic considerations and consequences for DNA repair inhibition. Chem Res Toxicol 21(3):600–606. https://doi.org/10.1021/tx7003135
Qin J, Rosen BP, Zhang Y, Wang G, Franke S, Rensing C (2006) Arsenic detoxification and evolution of trimethylarsine gas by a microbial arsenite S-adenosylmethionine methyltransferase. Proc Natl Acad Sci U S A 103(7):2075–2080
Raab A, Meharg AA, Jaspars M, Genney DR, Feldmann J (2004) Arsenic-glutathione complexes - their stability in solution and during separation by different HPLC modes. J Anal Atom Spectrom 19(1):183–190. https://doi.org/10.1039/b307945g
Raab A, Wright SH, Jaspars M, Meharg AA, Feldmann J (2007) Pentavalent arsenic can bind to biomolecules. Angew Chem Int Ed Engl 46(15):2594–2597
Rabieh S, Hirner AV, Matschullat J (2008) Determination of arsenic species in human urine using high performance liquid chromatography (HPLC) coupled with inductively coupled plasma mass spectrometry (ICP-MS). J Anal Atom Spectrom 23(4):544–549
Radabaugh TR, Aposhian HV (2000) Enzymatic reduction of arsenic compounds in mammalian systems: reduction of arsenate to arsenite by human liver arsenate reductase. Chem Res Toxicol 13(1):26–30
Ramadan D, Rancy PC, Nagarkar RP, Schneider JP, Thorpe C (2009) Arsenic(III) species inhibit oxidative protein folding in vitro. Biochemistry 48(2):424–432. https://doi.org/10.1021/bi801988x
Rasheed H, Slack R, Kay P (2016) Human health risk assessment for arsenic: a critical review. Crit Rev Environ Sci Technol 46(19–20):1529–1583. https://doi.org/10.1080/10643389.2016.1245551
Rosen B (2002) Biochemistry of arsenic detoxification. FEBS Lett 529(1):86–92. https://doi.org/10.1016/s0014-5793(02)03186-1
Rumpler A, Edmonds JS, Katsu M et al (2008) Arsenic-containing long-chain fatty acids in cod-liver oil: a result of biosynthetic infidelity? Angew Chem Int Ed Engl 47(14):2665–2667. https://doi.org/10.1002/anie.200705405
Sakurai T, Qu W, Sakurai MH, Waalkes MP (2002) A major human arsenic metabolite, dimethylarsinic acid, requires reduced glutathione to induce apoptosis. Chem Res Toxicol 15(5):629–637
Sakurai T, Kojima C, Kobayashi Y et al (2006) Toxicity of a trivalent organic arsenic compound, dimethylarsinous glutathione in a rat liver cell line (TRL 1215). Br J Pharmacol. 149(7):888–897. https://doi.org/10.1038/sj.bjp.0706899
Sampayo Reyes A, Zakharyan RA, Healy SM, Aposhian HV (2000) Monomethylarsonic acid reductase and monomethylarsonous acid in hamster tissue. Chem Res Toxicol 13(11):1181–1186
Savage L, Carey M, Williams P, Meharg A (2018) Biovolatilization of arsenic as arsines from seawater. Environ Sci Technol 52(7):3968–3974. https://doi.org/10.1021/acs.est.7b06456
Savage L, Carey M, Williams PN, Meharg AA (2019) Maritime deposition of organic and inorganic arsenic. Environ Sci Technol 53(13):7288–7295. https://doi.org/10.1021/acs.est.8b06335
Scott N, Hatlelid KM, MacKenzie NE, Carter DE (1993) Reactions of arsenic(III) and arsenic(V) species with glutathione. Chem Res Toxicol 6(1):102–106
Shen Z, Chen G, Ni J et al (1997) Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood 89(9):3354–3360
Shen S, Yang L, Lin H, Wu C, Su T, Chen Y (2008) Reactive oxygen species-dependent HSP90 protein cleavage participates in arsenical As(+3)- and MMA(+3)-induced apoptosis through inhibition of telomerase activity via JNK activation. Toxicol Appl Pharmacol 229(2):239–251. https://doi.org/10.1016/j.taap.2008.01.018
Shi K, Li C, Rensing C, Dai X, Fan X, Wang G (2018) Efflux transporter ArsK is responsible for bacterial resistance to arsenite, antimonite, trivalent roxarsone, and methylarsenite. Appl Environ Microbiol. https://doi.org/10.1128/AEM.01842-18
Shiobara Y, Ogra Y, Suzuki K (2001) Animal species difference in the uptake of dimethylarsinous acid (DMA(III)) by red blood cells. Chem Res Toxicol 14(10):1446–1452. https://doi.org/10.1021/tx015537k
Smith A, Lopipero P, Bates M, Steinmaus C (2002) Public health. Arsenic epidemiology and drinking water standards. Science 296(5576):2145–2146. https://doi.org/10.1126/science.1072896
Soignet S, Maslak P, Wang Z et al (1998) Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med 339(19):1341–1348. https://doi.org/10.1056/NEJM199811053391901
Soza-Ried C, Bustamante E, Caglevic C, Rolfo C, Sirera R, Marsiglia H (2019) Oncogenic role of arsenic exposure in lung cancer: a forgotten risk factor. Crit Rev Oncol Hematol 139:128–133. https://doi.org/10.1016/j.critrevonc.2019.01.012
Spuches AM, Kruszyna HG, Rich AM, Wilcox DE (2005) Thermodynamics of the As(III)-thiol interaction: arsenite and monomethylarsenite complexes with glutathione, dihydrolipoic acid, and other thiol ligands. Inorg Chem 44(8):2964–2972. https://doi.org/10.1021/ic048694q
Styblo M, Drobna Z, Jaspers I, Lin S, Thomas DJ (2002) The role of biomethylation in toxicity and carcinogenicity of arsenic: a research update. Environ Health Perspect 110:767–771
Styblo M, Douillet C, Bangma J, Eaves L (2019) Differential metabolism of inorganic arsenic in mice from genetically diverse collaborative cross strains. Arch Toxicol 93(10):2811–2822. https://doi.org/10.1007/s00204-019-02559-7
Sun H, Li H, Harvey I, Sadler P (1999) Interactions of bismuth complexes with metallothionein(II). J Biol Chem 274(41):29094–29101. https://doi.org/10.1074/jbc.274.41.29094
Suner MA, Devesa V, Munoz O, Velez D, Montoro R (2001) Application of column switching in high-performance liquid chromatography with on-line thermo-oxidation and detection by HG-AAS and HG-AFS for the analysis of organoarsenical species in seafood samples. J Anal Atom Spectrom 16(4):390–397. https://doi.org/10.1039/B007518n
Suzuki N, Naranmandura H, Hirano S, Suzuki KT (2008) Theoretical calculations and reaction analysis on the interaction of pentavalent thioarsenicals with biorelevant thiol compounds. Chem Res Toxicol 21(2):550–553. https://doi.org/10.1021/tx700346z
Twaddle N, Vanlandingham M, Fisher J, Doerge D (2018) Metabolism and disposition of arsenic species from controlled dosing with sodium arsenite in adult female CD-1 mice. III. Toxicokinetic studies following oral and intravenous administration. Food Chem Toxicol 121:676–686. https://doi.org/10.1016/j.fct.2018.09.068
Valenzuela OL, Borja-Aburto VH, Garcia-Vargas GG et al (2005) Urinary trivalent methylated arsenic species in a population chronically exposed to inorganic arsenic. Environ Health Perspect 113(3):250–254
Verma S, Verma PK, Pande V, Tripathi RD, Chakrabarty D (2016) Transgenic Arabidopsis thaliana expressing fungal arsenic methyltransferase gene (WaarsM) showed enhanced arsenic tolerance via volatilization. Environ Exp Bot 132:113–120. https://doi.org/10.1016/j.envexpbot.2016.08.012
Verma S, Verma PK, Meher AK, Bansiwal AK, Tripathi RD, Chakrabarty D (2018) A novel fungal arsenic methyltransferase, WaarsM reduces grain arsenic accumulation in transgenic rice (Oryza sativa L.). J Hazard Mater 344:626–634. https://doi.org/10.1016/j.jhazmat.2017.10.037
Villa-Bellosta R, Sorribas V (2010) Arsenate transport by sodium/phosphate cotransporter type IIb. Toxicol Appl Pharmacol 247(1):36–40. https://doi.org/10.1016/j.taap.2010.05.012
Von Recklinghausen U, Hartmann L, Rabieh S et al (2008) Methylated bismuth, but not bismuth citrate or bismuth glutathione, induces cyto- and genotoxic effects in human cells in vitro. Chem Res Toxicol 21(6):1219–1228. https://doi.org/10.1021/tx700304e
Waalkes MP, Liu J, Ward JM, Diwan BA (2004) Animal models for arsenic carcinogenesis: inorganic arsenic is a transplacental carcinogen in mice. Toxicol Appl Pharmacol 198(3):377–384
Wang Z, Zhang H, Li X, Le X (2007) Study of interactions between arsenicals and thioredoxins (human and E. coli) using mass spectrometry. Rapid Commun Mass Spectrom 21(22):3658–3666. https://doi.org/10.1002/rcm.3263
Wang XJ, Sun Z, Chen WM, Li YJ, Villeneuve NF, Zhang DD (2008) Activation of Nrf2 by arsenite and monomethylarsonous acid is independent of Keap1-C151: enhanced Keap1-Cul3 interaction. Toxicol Appl Pharmacol 230(3):383–389. https://doi.org/10.1016/j.taap.2008.03.003
Wang S, Li X, Song X, Geng Z, Hu X, Wang Z (2012) Rapid equilibrium kinetic analysis of arsenite methylation catalyzed by recombinant human arsenic (+3 oxidation state) methyltransferase (hAS3MT). J Biol Chem 287(46):38790–38799. https://doi.org/10.1074/jbc.M112.368050
Wang Q, Zhou X, Zhang Y et al (2015) Methylated arsenic metabolites bind to PML protein but do not induce cellular differentiation and PML-RARalpha protein degradation. Oncotarget 6(28):25646–25659. https://doi.org/10.18632/oncotarget.4662
Wanibuchi H, Yamamoto S, Chen H et al (1996) Promoting effects of dimethylarsinic acid on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in rats. Carcinogenesis 17(11):2435–2439
Watanabe T, Hirano S (2013) Metabolism of arsenic and its toxicological relevance. Arch Toxicol 87(6):969–979. https://doi.org/10.1007/s00204-012-0904-5
Wei M, Wanibuchi H, Yamamoto S, Li W, Fukushima S (1999) Urinary bladder carcinogenicity of dimethylarsinic acid in male F344 rats. Carcinogenesis 20(9):1873–1876
Wildfang E, Radabaugh TR, Aposhian HV (2001) Enzymatic methylation of arsenic compounds IX: liver arsenite methyltransferase and arsenate reductase activities in primates. Toxicology 168(3):213–221
Wolle MM, Conklin SD, Wittenberg J (2019) Matrix-induced transformation of arsenic species in seafoods. Anal Chim Acta 1060:53–63. https://doi.org/10.1016/j.aca.2019.02.027
Xue X, Ye J, Raber G et al (2019) Identification of steps in the pathway of arsenosugar biosynthesis. Environ Sci Technol 53(2):634–641. https://doi.org/10.1021/acs.est.8b04389
Yamamoto S, Konishi Y, Matsuda T et al (1995) Cancer induction by an organic arsenic compound, dimethylarsinic acid (cacodylic acid), in F344/DuCrj rats after pretreatment with five carcinogens. Cancer Res 55(6):1271–1276
Yamanaka K, Hoshino M, Okamoto M, Sawamura R, Hasegawa A, Okada S (1990) Induction of DNA damage by dimethylarsine, a metabolite of inorganic arsenics, is for the major part likely due to Its peroxyl radical. Biochem Biophys Res Commun 168(1):58–64
Yan H, Wang N, Weinfeld M, Cullen WR, Le XC (2009) Identification of arsenic-binding proteins in human cells by affinity chromatography and mass spectrometry. Anal Chem 81(10):4144–4152. https://doi.org/10.1021/ac900352k
Ye J, Chang Y, Yan Y et al (2014) Identification and characterization of the arsenite methyltransferase from a protozoan, Tetrahyrnena pyriformis. Aquat Toxicol 149:50–57. https://doi.org/10.1016/j.aquatox.2014.01.028
Yehiayan L, Pattabiraman M, Kavallieratos K, Wang XT, Boise LH, Cai Y (2009) Speciation, formation, stability and analytical challenges of human arsenic metabolites. J Anal Atom Spectrom 24(10):1397–1405
Yehiayan L, Membreno N, Matulis SM, Boise LH, Cai Y (2011) Extraction tool and matrix effects on arsenic speciation analysis in cell lines. Anal Chim Acta 699(2):187–192
Yokohira M, Arnold LL, Pennington KL et al (2010) Severe systemic toxicity and urinary bladder cytotoxicity and regenerative hyperplasia induced by arsenite in arsenic (+3 oxidation state) methyltransferase knockout mice. A preliminary report. Toxicol Appl Pharmacol 246(1–2):1–7. https://doi.org/10.1016/j.taap.2010.04.013
Yuan C, Lu X, Qin J, Rosen BP, Le XC (2008) Volatile arsenic species released from Escherichia coli expressing the AsIII S-adenosylmethionine methyltransferase gene. Environ Sci Technol 42(9):3201–3206
Zakharyan RA, Aposhian HV (1999) Arsenite methylation by methylvitamin B-12 and glutathione does not require an enzyme. Toxicol Appl Pharmacol 154(3):287–291
Zakharyan RA, Sampayo Reyes A, Healy SM et al (2001) Human monomethylarsonic acid (MMAV) reductase is a member of the glutathione-S-transferase superfamily. Chem Res Toxicol 14:1051–1057
Zhang XW, Yan XJ, Zhou ZR et al (2010) Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML. Science 328(5975):240–243. https://doi.org/10.1126/science.1183424
Zhang J, Cao TT, Tang Z, Shen QR, Rosen BP, Zhao FJ (2015) Arsenic methylation and volatilization by arsenite S-adenosylmethionine methyltransferase in pseudomonas alcaligenes NBRC14159. Appl Environ Microb 81(8):2852–2860. https://doi.org/10.1128/Aem.03804-14
Zhang J, Xu Y, Cao T, Chen J, Rosen B, Zhao F (2017) Arsenic methylation by a genetically engineered Rhizobium-legume symbiont. Plant Soil 416(1–2):259–269. https://doi.org/10.1007/s11104-017-3207-z
Zhou X, Sun X, Cooper KL, Wang F, Liu KJ, Hudson LG (2011) Arsenite interacts selectively with zinc finger proteins containing C3H1 or C4 motifs. J Biol Chem 286(26):22855–22863. https://doi.org/10.1074/jbc.M111.232926
Zhou J, Riccardi D, Beste A, Smith J, Parks J (2014) Mercury methylation by HgcA: theory supports carbanion transfer to Hg(II). Inorg Chem 53(2):772–777. https://doi.org/10.1021/ic401992y
Acknowledgements
This work was partially supported by a Grant-in-Aid from the Japan Society for the Promotion of Science (16K15386).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The author has no conflicts of interest regarding the contents of this article.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Hirano, S. Biotransformation of arsenic and toxicological implication of arsenic metabolites. Arch Toxicol 94, 2587–2601 (2020). https://doi.org/10.1007/s00204-020-02772-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00204-020-02772-9