An Overview of Arsenic Metabolism and Toxicity

Overview

Journal Curr Protoc Toxicol

Specialty Toxicology

Date 2014 Nov 25

PMID 25419261

Citations 35

Authors

Zuzana Drobna

Miroslav Styblo

David J Thomas

Affiliations

Soon will be listed here.

Abstract

It is likely that at least some of the toxic and carcinogenic effects associated with exposure to inorganic arsenic are, in fact, due to actions of its methylated metabolites. Here, we provide an overview of current models for the biological methylation of arsenicals. This information provides a context for understanding the chemical, biochemical, and genetic approaches to elucidation of the formation and function of metahylated arsenicals which are presented in the following manuscripts.

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References

TSENG W . Effects and dose--response relationships of skin cancer and blackfoot disease with arsenic. Environ Health Perspect. 1977; 19:109-19. PMC: 1637425. DOI: 10.1289/ehp.7719109. View

TSENG W, Chu H, How S, Fong J, Lin C, Yeh S . Prevalence of skin cancer in an endemic area of chronic arsenicism in Taiwan. J Natl Cancer Inst. 1968; 40(3):453-63. View

ENTERLINE P, Day R, Marsh G . Cancers related to exposure to arsenic at a copper smelter. Occup Environ Med. 1995; 52(1):28-32. PMC: 1128146. DOI: 10.1136/oem.52.1.28. View

Chen C, Wang S, Chiou J, Tseng C, Chiou H, Hsueh Y . Arsenic and diabetes and hypertension in human populations: a review. Toxicol Appl Pharmacol. 2007; 222(3):298-304. DOI: 10.1016/j.taap.2006.12.032. View

Lin S, Cullen W, Thomas D . Methylarsenicals and arsinothiols are potent inhibitors of mouse liver thioredoxin reductase. Chem Res Toxicol. 1999; 12(10):924-30. DOI: 10.1021/tx9900775. View

Waters S, Devesa V, Del Razo L, Styblo M, Thomas D . Endogenous reductants support the catalytic function of recombinant rat cyt19, an arsenic methyltransferase. Chem Res Toxicol. 2004; 17(3):404-9. DOI: 10.1021/tx0342161. View

Schwartz R . Paul Ehrlich's magic bullets. N Engl J Med. 2004; 350(11):1079-80. DOI: 10.1056/NEJMp048021. View

CHALLENGER F . Biological methylation. Adv Enzymol Relat Subj Biochem. 1951; 12:429-91. DOI: 10.1002/9780470122570.ch8. View

Navas-Acien A, Silbergeld E, Pastor-Barriuso R, Guallar E . Arsenic exposure and prevalence of type 2 diabetes in US adults. JAMA. 2008; 300(7):814-22. DOI: 10.1001/jama.300.7.814. View

10.

Le X, Ma M, Cullen W, APOSHIAN H, Lu X, Zheng B . Determination of monomethylarsonous acid, a key arsenic methylation intermediate, in human urine. Environ Health Perspect. 2000; 108(11):1015-8. PMC: 1240155. DOI: 10.1289/ehp.001081015. View

11.

Wei M, Wanibuchi H, Yamamoto S, Li W, Fukushima S . Urinary bladder carcinogenicity of dimethylarsinic acid in male F344 rats. Carcinogenesis. 1999; 20(9):1873-6. DOI: 10.1093/carcin/20.9.1873. View

12.

Yamamoto S, Konishi Y, Matsuda T, Murai T, Shibata M, Matsui-Yuasa I . Cancer induction by an organic arsenic compound, dimethylarsinic acid (cacodylic acid), in F344/DuCrj rats after pretreatment with five carcinogens. Cancer Res. 1995; 55(6):1271-6. View

13.

Smith A, Lingas E, Rahman M . Contamination of drinking-water by arsenic in Bangladesh: a public health emergency. Bull World Health Organ. 2000; 78(9):1093-103. PMC: 2560840. View

14.

Waters S, Devesa V, Fricke M, Creed J, Styblo M, Thomas D . Glutathione modulates recombinant rat arsenic (+3 oxidation state) methyltransferase-catalyzed formation of trimethylarsine oxide and trimethylarsine. Chem Res Toxicol. 2004; 17(12):1621-9. DOI: 10.1021/tx0497853. View

15.

Bhattacharjee Y . Toxicology. A sluggish response to humanity's biggest mass poisoning. Science. 2007; 315(5819):1659-61. DOI: 10.1126/science.315.5819.1659. View

16.

Wright M, Bruford E . Human and orthologous gene nomenclature. Gene. 2006; 369:1-6. DOI: 10.1016/j.gene.2005.10.029. View

17.

Naranmandura H, Suzuki N, Suzuki K . Trivalent arsenicals are bound to proteins during reductive methylation. Chem Res Toxicol. 2006; 19(8):1010-8. DOI: 10.1021/tx060053f. View

18.

Lubin J, Pottern L, Stone B, Fraumeni Jr J . Respiratory cancer in a cohort of copper smelter workers: results from more than 50 years of follow-up. Am J Epidemiol. 2000; 151(6):554-65. DOI: 10.1093/oxfordjournals.aje.a010243. View

19.

Douer D, Tallman M . Arsenic trioxide: new clinical experience with an old medication in hematologic malignancies. J Clin Oncol. 2005; 23(10):2396-410. DOI: 10.1200/JCO.2005.10.217. View

20.

Lin S, Del Razo L, Styblo M, Wang C, Cullen W, Thomas D . Arsenicals inhibit thioredoxin reductase in cultured rat hepatocytes. Chem Res Toxicol. 2001; 14(3):305-11. DOI: 10.1021/tx0001878. View