Importance of being thiomethylated: Formation, fate, and effects of methylated thioarsenicals

Chemical Research in Toxicology

Volumn 28, Issue 3, 2015, Pages 281-289

  Wang, Qian Qian ^a,b   Thomas, David J ^c   Naranmandura, Hua ^a,b  

^a School of Medicine and Public Health   (China)

^b ZHEJIANG UNIVERSITY   (China)

^c U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARSENIC DERIVATIVE; HYDROGEN SULFIDE; OXYGEN; ORGANOARSENIC DERIVATIVE; THIOL DERIVATIVE;

ATOM; CHEMICAL REACTION; CYTOTOXICITY; ENVIRONMENTAL FACTOR; ENZYMOLOGY; HUMAN; LONG TERM EXPOSURE; METABOLISM; METABOLITE; METHYLATION; NONHUMAN; REVIEW; ANIMAL; ARSENIC POISONING;

ANIMALIA;

ANIMALS; ARSENIC POISONING; ARSENICALS; HUMANS; METHYLATION; SULFHYDRYL COMPOUNDS;

EID: 84924915505     PISSN: 0893228X     EISSN: 15205010     Source Type: Journal    
DOI: 10.1021/tx500464t     Document Type: Review

References (109)

1. Bouteille, B., Oukem, O., Bisser, S., and Dumas, M. (2003) Treatment perspectives for human African trypanosomiasis Fundam. Clin. Pharmacol. 17, 171-181
2. Powell, B. L., Moser, B., Stock, W., Gallagher, R. E., Willman, C. L., Stone, R. M., Rowe, J. M., Coutre, S., Feusner, J. H., and Gregory, J. (2010) Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710 Blood 116, 3751-3757
3. Powell, B. L. (2011) Arsenic trioxide in acute promyelocytic leukemia: potion not poison Expert Rev. Anticancer 11, 1317-1319
4. IARC (2004) Some drinking-water disinfectants and contaminants, including arsenic. IARC Monogr. Eval. Carcinog. Risks Hum. 84, 1.
5. Hong, Y.-S., Song, K.-H., and Chung, J.-Y. (2014) Health effects of chronic arsenic exposure Am. J. Prev. Med. 47, 245
6. Wang, W., Cheng, S., and Zhang, D. (2014) Association of inorganic arsenic exposure with liver cancer mortality: a meta-analysis Environ. Res. 135, 120-125
7. Saint-Jacques, N., Parker, L., Brown, P., and Dummer, T. J. (2014) Arsenic in drinking water and urinary tract cancers: a systematic review of 30 years of epidemiological evidence Environ. Health 13, 44
8. Moon, K., Guallar, E., and Navas-Acien, A. (2012) Arsenic exposure and cardiovascular disease: an updated systematic review Curr. Atheroscler. Rep. 14, 542-555
9. Farzan, S. F., Karagas, M. R., and Chen, Y. (2013) In utero and early life arsenic exposure in relation to long-term health and disease Toxicol. Appl. Pharmacol. 272, 384-390
10. Chung, J. Y., Yu, S. D., and Hong, Y. S. (2014) Environmental source of arsenic exposure J. Prev. Med. Public Health 47, 253-257
11. Shankar, S., Shanker, U., and Shikha (2014) Arsenic contamination of groundwater: a review of sources, prevalence, health risks, and strategies for mitigation Sci. World J. 2014, 304524
12. Watanabe, T. and Hirano, S. (2013) Metabolism of arsenic and its toxicological relevance Arch. Toxicol. 87, 969-979
13. Zhu, Y.-G., Yoshinaga, M., Zhao, F.-J., and Rosen, B. P. (2014) Earth abides arsenic biotransformations Annu. Rev. Earth Planet Sci. 42, 443-467
14. Challenger, F. (1945) Biological methylation Chem. Rev. 36, 315-361
15. Petrick, J. S., Ayala-Fierro, F., Cullen, W. R., Carter, D. E., and Aposhian, H. V. (2000) Monomethylarsonous acid (MMA(III)) is more toxic than arsenite in Chang human hepatocytes Toxicol. Appl. Pharmacol. 163, 203-207
16. Styblo, M., Del Razo, L. M., Vega, L., Germolec, D. R., LeCluyse, E. L., Hamilton, G. A., Reed, W., Wang, C., Cullen, W. R., and Thomas, D. J. (2000) Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells Arch. Toxicol. 74, 289-299
17. III)-induced cytotoxicity Toxicol. Appl. Pharmacol. 260, 241-249
18. Zhang, Y. F., Zhang, M., Huang, X. L., Fu, Y. J., Jiang, Y. H., Bao, L. L., Maimaitiyiming, Y., Zhang, J. G., Wang, Q. Q., and Naranmandura, H. (2014) Combination of arsenic and cryptotanshinone induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in breast cancer cells Metallomics 7, 165-173
19. Rehman, K., Fu, Y. J., Zhang, Y. F., Wang, Q. Q., Wu, B., Wu, Y., Zhou, X. Y., Sun, W. H., Sun, T. F., and Naranmandura, H. (2014) Trivalent methylated arsenic metabolites induce apoptosis in human myeloid leukemic HL-60 cells through generation of reactive oxygen species Metallomics 6, 1502-1512
20. Antonelli, R., Shao, K., Thomas, D. J., Sams, R., and Cowden, J. (2014) AS3MT, GSTO, and PNP polymorphisms: impact on arsenic methylation and implications for disease susceptibility Environ. Res. 132, 156-167
21. Hayakawa, T., Kobayashi, Y., Cui, X., and Hirano, S. (2005) A new metabolic pathway of arsenite: arsenic-glutathione complexes are substrates for human arsenic methyltransferase Cyt19 Arch. Toxicol. 79, 183-191
22. Naranmandura, H., Suzuki, N., and Suzuki, K. T. (2006) Trivalent arsenicals are bound to proteins during reductive methylation Chem. Res. Toxicol. 19, 1010-1018
23. Cullen, W. R. (2014) Chemical mechanism of arsenic biomethylation Chem. Res. Toxicol. 27, 457-461
24. Ajees, A. A., Marapakala, K., Packianathan, C., Sankaran, B., and Rosen, B. P. (2012) Structure of an As(III) S-adenosylmethionine methyltransferase: insights into the mechanism of arsenic biotransformation Biochemistry 51, 5476-5485
25. Dheeman, D. S., Packianathan, C., Pillai, J. K., and Rosen, B. P. (2014) Pathway of human AS3MT arsenic methylation Chem. Res. Toxicol. 27, 1979-1989
26. Naranmandura, H. (2014) Letter to the Editor regarding the article by Dheeman et al., 2014 Chem. Res. Toxicol. 27, 2011
27. Thomas, D. J. and Rosen, B. P. (2013) Arsenic Methyltransferases, in Encyclopedia of Metalloproteins pp 138-143, Springer, New York.
28. Ding, L., Saunders, R. J., Drobna, Z., Walton, F. S., Xun, P., Thomas, D. J., and Styblo, M. (2012) Methylation of arsenic by recombinant human wild-type arsenic (+3 oxidation state) methyltransferase and its methionine 287 threonine (M287T) polymorph: Role of glutathione Toxicol. Appl. Pharmacol. 264, 121-130
29. Thomas, D. J., Li, J., Waters, S. B., Xing, W., Adair, B. M., Drobna, Z., Devesa, V., and Styblo, M. (2007) Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals Exp. Biol. Med. 232, 3-13
30. Drobna, Z., Naranmandura, H., Kubachka, K. M., Edwards, B. C., Herbin-Davis, K., Styblo, M., Le, X. C., Creed, J. T., Maeda, N., Hughes, M. F., and Thomas, D. J. (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, 1713-1720
31. Hughes, M. F., Edwards, B. C., Herbin-Davis, K. M., Saunders, J., Styblo, M., and Thomas, D. J. (2010) Arsenic (+3 oxidation state) methyltransferase genotype affects steady-state distribution and clearance of arsenic in arsenate-treated mice Toxicol. Appl. Pharmacol. 249, 217-223
32. Chen, B., Arnold, L. L., Cohen, S. M., Thomas, D. J., and Le, X. C. (2011) Mouse arsenic (+ 3 oxidation state) methyltransferase genotype affects metabolism and tissue dosimetry of arsenicals after arsenite administration in drinking water Toxicol. Sci. 124, 320-326
33. Yokohira, M., Arnold, L. L., Pennington, K. L., Suzuki, S., Kakiuchi-Kiyota, S., Herbin-Davis, K., Thomas, D. J., and Cohen, S. M. (2011) Effect of sodium arsenite dose administered in the drinking water on the urinary bladder epithelium of female arsenic (+3 oxidation state) methyltransferase knockout mice Toxicol. Sci. 121, 257-266
34. Naranmandura, H., Suzuki, N., Iwata, K., Hirano, S., and Suzuki, K. T. (2007) Arsenic metabolism and thioarsenicals in hamsters and rats Chem. Res. Toxicol. 20, 616-624
35. Planer-Friedrich, B., Suess, E., Scheinost, A. C., and Wallschlager, D. (2010) Arsenic speciation in sulfidic waters: reconciling contradictory spectroscopic and chromatographic evidence Anal. Chem. 82, 10228-10235
36. Mandal, B. K. and Suzuki, K. T. (2002) Arsenic round the world: a review Talanta 58, 201-235
37. Wallschlager, D. and Stadey, C. J. (2007) Determination of (Oxy)thioarsenates in sulfidic waters Anal. Chem. 79, 3873-3880
38. Qin, J., Lehr, C. R., Yuan, C. G., Le, X. C., McDermott, T. R., and Rosen, B. P. (2009) Biotransformation of arsenic by a Yellowstone thermoacidophilic eukaryotic alga Proc. Natl. Acad. Sci. U.S.A. 106, 5213-5217
39. Gong, Z., Lu, X., Cullen, W. R., and Le, X. C. (2001) Unstable trivalent arsenic metabolites, monomethylarsonous acid and dimethylarsinous acid J. Anal. At. Spectrom. 16, 1409-1413
40. Gong, Z., Lu, X., Ma, M., Watt, C., and Le, X. C. (2002) Arsenic speciation analysis Talanta 58, 77-96
41. McCleskey, R. B., Nordstrom, D. K., and Maest, A. S. (2004) Preservation of water samples for arsenic (III/V) determinations: an evaluation of the literature and new analytical results Appl. Geochem. 19, 995-1009
42. Cheam, V. and Agemian, H. (1980) Preservation of inorganic arsenic species at microgram levels in water samples Analyst 105, 737-743
43. Planer-Friedrich, B. and Wallschlager, D. (2009) A critical investigation of hydride generation-based arsenic speciation in sulfidic waters Environ. Sci. Technol. 43, 5007-5013
44. Raml, R., Rumpler, A., Goessler, W., Vahter, M., Li, L., Ochi, T., and Francesconi, K. A. (2007) Thio-dimethylarsinate is a common metabolite in urine samples from arsenic-exposed women in Bangladesh Toxicol. Appl. Pharmacol. 222, 374-380
45. Conklin, S. D., Fricke, M. W., Creed, P. A., and Creed, J. T. (2008) Investigation of the pH effects on the formation of methylated thio-arsenicals, and the effects of pH and temperature on their stability J. Anal. At. Spectrom. 23, 711-716
46. Raml, R., Goessler, W., Traar, P., Ochi, T., and Francesconi, K. A. (2005) Novel thioarsenic metabolites in human urine after ingestion of an arsenosugar, 2′,3′-dihydroxypropyl 5-deoxy-5-dimethylarsinoyl-beta-D-riboside Chem. Res. Toxicol. 18, 1444-1450
47. Bhymer, C. and Caruso, J. A. (2004) Arsenic and its speciation analysis using high-performance liquid chromatography and inductively coupled plasma mass spectrometry J. Chromatogr., A 1045, 1-13
48. Adair, B. M., Moore, T., Conklin, S. D., Creed, J. T., Wolf, D. C., and Thomas, D. J. (2007) Tissue distribution and urinary excretion of dimethylated arsenic and its metabolites in dimethylarsinic acid- or arsenate-treated rats Toxicol. Appl. Pharmacol. 222, 235-242
49. Suzuki, S., Arnold, L. L., Pennington, K. L., Chen, B., Naranmandura, H., Le, X. C., and Cohen, S. M. (2010) Dietary administration of sodium arsenite to rats: relations between dose and urinary concentrations of methylated and thio-metabolites and effects on the rat urinary bladder epithelium Toxicol. Appl. Pharmacol. 244, 99-105
50. Naranmandura, H., Rehman, K., Le, X. C., and Thomas, D. J. (2013) Formation of methylated oxyarsenicals and thioarsenicals in wild-type and arsenic (+3 oxidation state) methyltransferase knockout mice exposed to arsenate Anal. Bioanal. Chem. 405, 1885-1891
51. Hansen, H. R., Raab, A., Jaspars, M., Milne, B. F., and Feldmann, J. (2004) Sulfur-containing arsenical mistaken for dimethylarsinous acid [DMA(III)] and identified as a natural metabolite in urine: major implications for studies on arsenic metabolism and toxicity Chem. Res. Toxicol. 17, 1086-1091
52. Hansen, H. R., Pickford, R., Thomas-Oates, J., Jaspars, M., and Feldmann, J. (2004) 2-Dimethylarsinothioyl acetic acid identified in a biological sample: the first occurrence of a mammalian arsinothioyl metabolite Angew. Chem., Int. Ed. 116, 341-344
53. Fricke, M. W., Zeller, M., Sun, H., Lai, V. W., Cullen, W. R., Shoemaker, J. A., Witkowski, M. R., and Creed, J. T. (2005) Chromatographic separation and identification of products from the reaction of dimethylarsinic acid with hydrogen sulfide Chem. Res. Toxicol. 18, 1821-1829
54. Orthaber, A., Sax, A. F., and Francesconi, K. A. (2012) Oxygen versus sulfur: structure and reactivity of substituted arsine oxides and arsine sulfides J. Comput. Chem. 33, 112-117
55. Suarez, F., Furne, J., Springfield, J., and Levitt, M. (1998) Production and elimination of sulfur-containing gases in the rat colon Am. J. Physiol.: Gastrointest. Liver Physiol. 274, G727-G733
56. Shen, X., Carlstrom, M., Borniquel, S., Jadert, C., Kevil, C. G., and Lundberg, J. O. (2013) Microbial regulation of host hydrogen sulfide bioavailability and metabolism Free Radical Biol. Med. 60, 195-200
57. Martin, G. R., McKnight, G. W., Dicay, M. S., Coffin, C. S., Ferraz, J. G. P., and Wallace, J. L. (2010) Hydrogen sulphide synthesis in the rat and mouse gastrointestinal tract Dig. Liver Dis. 42, 103-109
58. 2S biogenesis, decay and signaling Antioxid. Redox Signaling 20, 770-782
59. Gadalla, M. M. and Snyder, S. H. (2010) Hydrogen sulfide as a gasotransmitter J. Neurosci. 113, 14-26
60. Teague, B., Asiedu, I., and Moore, P. K. (2002) The smooth muscle relaxant effect of hydrogen sulphide in vitro: evidence for a physiological role to control intestinal contractility Br. J. Pharmacol. 137, 139-145
61. 2S as a novel endogenous gaseous K-ATP channel opener EMBO J. 20, 6008-6016
62. Abe, K. and Kimura, H. (1996) The possible role of hydrogen sulfide as an endogenous neuromodulator J. Neurosci. 16, 1066-1071
63. 2S biogenesis Biochim. Biophys. Acta 1814, 1518-1527
64. Benavides, G. A., Squadrito, G. L., Mills, R. W., Patel, H. D., Isbell, T. S., Patel, R. P., Darley-Usmar, V. M., Doeller, J. E., and Kraus, D. W. (2007) Hydrogen sulfide mediates the vasoactivity of garlic Proc. Natl. Acad. Sci. U.S.A. 104, 17977-17982
65. 2S biogenesis via alternative trans-sulfuration reactions J. Biol. Chem. 284, 22457-22466
66. 2S in the gastrointestinal tract: still in search of a physiologic function Antioxid. Redox Signaling 12, 1135-1146
67. Furne, J., Saeed, A., and Levitt, M. D. (2008) Whole tissue hydrogen sulfide concentrations are orders of magnitude lower than presently accepted values Am. J. Physiol.: Regul., Integr. Comp. Physiol. 295, R1479-R1485
68. Linden, D. R., Sha, L., Mazzone, A., Stoltz, G. J., Bernard, C. E., Furne, J. K., Levitt, M. D., Farrugia, G., and Szurszewski, J. H. (2008) Production of the gaseous signal molecule hydrogen sulfide in mouse tissues J. Neurosci. 106, 1577-1585
69. Weisiger, R. A., Pinkus, L. M., and Jakoby, W. B. (1980) Thiol S-methyltransferase-suggested role in detoxication of intestinal hydrogen-sulfide Biochem. Pharmacol. 29, 2885-2887
70. Furne, J., Springfield, J., Koenig, T., DeMaster, E., and Levitt, M. D. (2001) Oxidation of hydrogen sulfide and methanethiol to thiosulfate by rat tissues: a specialized function of the colonic mucosa Biochem. Pharmacol. 62, 255-259
71. Levitt, M. D., Furne, J., Springfield, J., Suarez, F., and DeMaster, E. (1999) Detoxification of hydrogen sulfide and methanethiol in the cecal mucosa J. Clin. Invest. 104, 1107-1114
72. Libiad, M., Yadav, P. K., Vitvitsky, V., Martinov, M., and Banerjee, R. (2014) Organization of the human mitochondrial hydrogen sulfide oxidation pathway J. Biol. Chem. 289, 30901-30910
73. Rowland, I. and Davies, M. (1981) In vitro metabolism of inorganic arsenic by the gastro-intestinal microflora of the rat J. Appl. Toxicol. 1, 278-283
74. Hall, L. L., George, S. E., Kohan, M. J., Styblo, M., and Thomas, D. J. (1997) In vitro methylation of inorganic arsenic in mouse intestinal cecum Toxicol. Appl. Pharmacol. 147, 101-109
75. Van de Wiele, T., Gallawa, C. M., Kubachka, K. M., Creed, J. T., Basta, N., Dayton, E. A., Whitacre, S., Du Laing, G., and Bradham, K. (2010) Arsenic metabolism by human gut microbiota upon in vitro digestion of contaminated soils Environ. Health Perspect. 118, 1004-1009
76. Conklin, S. D., Ackerman, A. H., Fricke, M. W., Creed, P. A., Creed, J. T., Kohan, M. C., Herbin-Davis, K., and Thomas, D. J. (2006) In vitro biotransformation of an arsenosugar by mouse anaerobic cecal microflora and cecal tissue as examined using IC-ICP-MS and LC-ESI-MS/MS Analyst 131, 648-655
77. Leffers, L., Ebert, F., Taleshi, M. S., Francesconi, K. A., and Schwerdtle, T. (2013) In vitro toxicological characterization of two arsenosugars and their metabolites Mol. Nutr. Food Res. 57, 1270-1282
78. Leffers, L., Wehe, C. A., Huwel, S., Bartel, M., Ebert, F., Taleshi, M. S., Galla, H. J., Karst, U., Francesconi, K. A., and Schwerdtle, T. (2013) In vitro intestinal bioavailability of arsenosugar metabolites and presystemic metabolism of thio-dimethylarsinic acid in Caco-2 cells Metallomics 5, 1031-1042
79. Kubachka, K. M., Kohan, M. C., Conklin, S. D., Herbin-Davis, K., Creed, J. T., and Thomas, D. J. (2009) In vitro biotransformation of dimethylarsinic acid and trimethylarsine oxide by anaerobic microflora of mouse cecum analyzed by HPLC-ICP-MS and HPLC-ESI-MS J. Anal. At. Spectrom. 24, 1062-1068
80. Kubachka, K. M., Kohan, M. C., Herbin-Davis, K., Creed, J. T., and Thomas, D. J. (2009) Exploring the in vitro formation of trimethylarsine sulfide from dimethylthioarsinic acid in anaerobic microflora of mouse cecum using HPLC-ICP-MS and HPLC-ESI-MS Toxicol. Appl. Pharmacol. 239, 137-143
81. Pinyayev, T. S., Kohan, M. J., Herbin-Davis, K., Creed, J. T., and Thomas, D. J. (2011) Preabsorptive metabolism of sodium arsenate by anaerobic microbiota of mouse cecum forms a variety of methylated and thiolated arsenicals Chem. Res. Toxicol. 24, 475-477
82. Suzuki, K. T., Mandal, B. K., Katagiri, A., Sakuma, Y., Kawakami, A., Ogra, Y., Yamaguchi, K., Sei, Y., Yamanaka, K., Anzai, K., Ohmichi, M., Takayama, H., and Aimi, N. (2004) Dimethylthioarsenicals as arsenic metabolites and their chemical preparations Chem. Res. Toxicol. 17, 914-921
83. Naranmandura, H. and Suzuki, K. T. (2008) Formation of dimethylthioarsenicals in red blood cells Toxicol. Appl. Pharmacol. 227, 390-399
84. Hansen, H. R., Jaspars, M., and Feldmann, J. (2004) Arsinothioyl-sugars produced by in vitro incubation of seaweed extract with liver cytosol analysed by HPLC coupled simultaneously to ES-MS and ICP-MS Analyst 129, 1058-1064
85. Bu, N., Wang, H. Y., Hao, W. H., Liu, X., Xu, S., Wu, B., Anan, Y., Ogra, Y., Lou, Y. J., and Naranmandura, H. (2011) Generation of thioarsenicals is dependent on the enterohepatic circulation in rats Metallomics 3, 1064-1073
86. Rehman, K., Chen, Z., Wang, W. W., Wang, Y. W., Sakamoto, A., Zhang, Y. F., Naranmandura, H., and Suzuki, N. (2012) Mechanisms underlying the inhibitory effects of arsenic compounds on protein tyrosine phosphatase (PTP) Toxicol. Appl. Pharmacol. 263, 273-280
87. Suzuki, K. T., Tomita, T., Ogra, Y., and Ohmichi, M. (2001) Glutathione-conjugated arsenics in the potential hepato-enteric circulation in rats Chem. Res. Toxicol. 14, 1604-1611
88. Kala, S. V., Kala, G., Prater, C. I., Sartorelli, A. C., and Lieberman, M. W. (2004) Formation and urinary excretion of arsenic triglutathione and methylarsenic diglutathione Chem. Res. Toxicol. 17, 243-249
89. Banerjee, M., Carew, M. W., Roggenbeck, B. A., Whitlock, B. D., Naranmandura, H., Le, X. C., and Leslie, E. M. (2014) A novel pathway for arsenic elimination: human multidrug resistance protein 4 (MRP4/ABCC4) mediates cellular export of dimethylarsinic acid (DMAV) and the diglutathione conjugate of monomethylarsonous acid (MMAIII) Mol. Pharmacol. 86, 168-79
90. Carew, M. W., Naranmandura, H., Shukalek, C. B., Le, X. C., and Leslie, E. M. (2011) Monomethylarsenic diglutathione transport by the human multidrug resistance protein 1 (MRP1/ABCC1) Drug Metab. Dispos. 39, 2298-2304
91. Raab, A., Wright, S. H., Jaspars, M., Meharg, A. A., and Feldmann, J. (2007) Pentavalent arsenic can bind to biomolecules Angew. Chem., Int. Ed. 46, 2594-2597
92. Yehiayan, L., Stice, S., Liu, G. L., Matulis, S., Boise, L. H., and Cai, Y. (2014) Dimethylarsinothioyl glutathione as a metabolite in human multiple myeloma cell lines upon exposure to darinaparsin Chem. Res. Toxicol. 27, 754-764
93. Suzuki, K. T., Iwata, K., Naranmandura, H., and Suzuki, N. (2007) Metabolic differences between two dimethylthioarsenicals in rats Toxicol. Appl. Pharmacol. 218, 166-173
94. Naranmandura, H., Bu, N., Suzuki, K. T., Lou, Y., and Ogra, Y. (2010) Distribution and speciation of arsenic after intravenous administration of monomethylmonothioarsonic acid in rats Chemosphere 81, 206-213
95. Naranmandura, H., Iwata, K., Suzuki, K. T., and Ogra, Y. (2010) Distribution and metabolism of four different dimethylated arsenicals in hamsters Toxicol. Appl. Pharmacol. 245, 67-75
96. Naranmandura, H., Ibata, K., and Suzuki, K. T. (2007) Toxicity of dimethylmonothioarsinic acid toward human epidermoid carcinoma A431 cells Chem. Res. Toxicol. 20, 1120-1125
97. Ochi, T., Kita, K., Suzuki, T., Rumpler, A., Goessler, W., and Francesconi, K. A. (2008) Cytotoxic, genotoxic and cell-cycle disruptive effects of thio-dimethylarsinate in cultured human cells and the role of glutathione Toxicol. Appl. Pharmacol. 228, 59-67
98. Naranmandura, H., Carew, M. W., Xu, S., Lee, J., Leslie, E. M., Weinfeld, M., and Le, X. C. (2011) Comparative toxicity of arsenic metabolites in human bladder cancer EJ-1 cells Chem. Res. Toxicol. 24, 1586-1596
99. Naranmandura, H., Ogra, Y., Iwata, K., Lee, J., Suzuki, K. T., Weinfeld, M., and Le, X. C. (2009) Evidence for toxicity differences between inorganic arsenite and thioarsenicals in human bladder cancer cells Toxicol. Appl. Pharmacol. 238, 133-140
100. Leffers, L., Unterberg, M., Bartel, M., Hoppe, C., Pieper, I., Stertmann, J., Ebert, F., Humpf, H. U., and Schwerdtle, T. (2013) In vitro toxicological characterisation of the S-containing arsenic metabolites thio-dimethylarsinic acid and dimethylarsinic glutathione Toxicology 305, 109-119
101. Ebert, F., Leffers, L., Weber, T., Berndt, S., Mangerich, A., Beneke, S., Burkle, A., and Schwerdtle, T. (2014) Toxicological properties of the thiolated inorganic arsenic and arsenosugar metabolite thio-dimethylarsinic acid in human bladder cells J. Trace Elem. Med. Biol. 28, 138-146
102. Wei, M., Wanibuchi, H., Morimura, K., Iwai, S., Yoshida, K., Endo, G., Nakae, D., and Fukushima, S. (2002) Carcinogenicity of dimethylarsinic acid in male F344 rats and genetic alterations in induced urinary bladder tumors Carcinogenesis 23, 1387-1397
103. Cohen, S. M., Ohnishi, T., Arnold, L. L., and Le, X. C. (2007) Arsenic-induced bladder cancer in an animal model Toxicol. Appl. Pharmacol. 222, 258-263
104. Cohen, S. M., Arnold, L. L., Uzvolgyi, E., Cano, M., St John, M., Yamamoto, S., Lu, X., and Le, X. C. (2002) Possible role of dimethylarsinous acid in dimethylarsinic acid-induced urothelial toxicity and regeneration in the rat Chem. Res. Toxicol. 15, 1150-1157
105. Cohen, S. M., Yamamoto, S., Cano, M., and Arnold, L. L. (2001) Urothelial cytotoxicity and regeneration induced by dimethylarsinic acid in rats Toxicol. Sci. 59, 68-74
106. Cohen, S. M., Arnold, L. L., Eldan, M., Lewis, A. S., and Beck, B. D. (2006) Methylated arsenicals: the implications of metabolism and carcinogenicity studies in rodents to human risk assessment Crit. Rev. Toxicol. 36, 99-133
107. Shen, J., Wanibuchi, H., Salim, E. I., Wei, M., Kinoshita, A., Yoshida, K., Endo, G., and Fukushima, S. (2003) Liver tumorigenicity of trimethylarsine oxide in male Fischer 344 rats - association with oxidative DNA damage and enhanced cell proliferation Carcinogenesis 24, 1827-1835
108. Yoshida, K., Kuroda, K., Zhou, X., Inoue, Y., Date, Y., Wanibuchi, H., Fukushima, S., and Endo, G. (2003) Urinary sulfur-containing metabolite produced by intestinal bacteria following oral administration of dimethylarsinic acid to rats Chem. Res. Toxicol. 16, 1124-1129
109. Kenyon, E. M., Hughes, M. F., Adair, B. M., Highfill, J. H., Crecelius, E. A., Clewell, H. J., and Yager, J. W. (2008) Tissue distribution and urinary excretion of inorganic arsenic and its methylated metabolites in C57BL6 mice following subchronic exposure to arsenate in drinking water Toxicol. Appl. Pharmacol. 232, 448-455