Urinary Trivalent Methylated Arsenic Species in a Population Chronically Exposed to Inorganic Arsenic

Overview

Journal Environ Health Perspect

Date 2005 Mar 4

PMID 15743710

Citations 78

Authors

Olga L Valenzuela

Victor H Borja-Aburto

Gonzalo G Garcia-Vargas

Martha B Cruz-Gonzalez

Eliud A Garcia-Montalvo

Emma S Calderon-Aranda

Luz M Del Razo

Affiliations

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Abstract

Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. In this study we examined the relationship between urinary profiles of MAsIII and DMAsIII and skin lesion markers of iAs toxicity in individuals exposed to iAs in drinking water. The study subjects were recruited among the residents of an endemic region of central Mexico. Drinking-water reservoirs in this region are heavily contaminated with iAs. Previous studies carried out in the local populations have found an increased incidence of pathologies, primarily skin lesions, that are characteristic of arseniasis. The goal of this study was to investigate the urinary profiles for the trivalent and pentavalent As metabolites in both high- and low-iAs-exposed subjects. Notably, methylated trivalent arsenicals were detected in 98% of analyzed urine samples. On average, the major metabolite, DMAsIII, represented 49% of total urinary As, followed by DMAsV (23.7%), iAsV (8.6%), iAsIII (8.5%), MAsIII (7.4%), and MAsV (2.8%). More important, the average MAsIII concentration was significantly higher in the urine of exposed individuals with skin lesions compared with those who drank iAs-contaminated water but had no skin lesions. These data suggest that urinary levels of MAsIII, the most toxic species among identified metabolites of iAs, may serve as an indicator to identify individuals with increased susceptibility to toxic and cancer-promoting effects of arseniasis.

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References

Del Razo L, Arellano M, Cebrian M . The oxidation states of arsenic in well-water from a chronic arsenicism area of northern Mexico. Environ Pollut. 1990; 64(2):143-53. DOI: 10.1016/0269-7491(90)90111-o. View

Vega L, Styblo M, Patterson R, Cullen W, Wang C, Germolec D . Differential effects of trivalent and pentavalent arsenicals on cell proliferation and cytokine secretion in normal human epidermal keratinocytes. Toxicol Appl Pharmacol. 2001; 172(3):225-32. DOI: 10.1006/taap.2001.9152. View

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

Thomas D, Waters S, Styblo M . Elucidating the pathway for arsenic methylation. Toxicol Appl Pharmacol. 2004; 198(3):319-26. DOI: 10.1016/j.taap.2003.10.020. View

Zakharyan R, Sampayo-Reyes A, Healy S, Tsaprailis G, Board P, Liebler D . Human monomethylarsonic acid (MMA(V)) reductase is a member of the glutathione-S-transferase superfamily. Chem Res Toxicol. 2001; 14(8):1051-7. DOI: 10.1021/tx010052h. View

Csanaky I, Gregus Z . Species variations in the biliary and urinary excretion of arsenate, arsenite and their metabolites. Comp Biochem Physiol C Toxicol Pharmacol. 2002; 131(3):355-65. DOI: 10.1016/s1532-0456(02)00018-2. View

Radabaugh T, Sampayo-Reyes A, Zakharyan R, Aposhian H . Arsenate reductase II. Purine nucleoside phosphorylase in the presence of dihydrolipoic acid is a route for reduction of arsenate to arsenite in mammalian systems. Chem Res Toxicol. 2002; 15(5):692-8. DOI: 10.1021/tx0101853. View

Mass M, Tennant A, Roop B, Cullen W, Styblo M, Thomas D . Methylated trivalent arsenic species are genotoxic. Chem Res Toxicol. 2001; 14(4):355-61. DOI: 10.1021/tx000251l. View

Schwartz R . Arsenic and the skin. Int J Dermatol. 1997; 36(4):241-50. DOI: 10.1046/j.1365-4362.1997.00101.x. View

10.

APOSHIAN H, Arroyo A, Cebrian M, Del Razo L, Hurlbut K, Dart R . DMPS-arsenic challenge test. I: Increased urinary excretion of monomethylarsonic acid in humans given dimercaptopropane sulfonate. J Pharmacol Exp Ther. 1997; 282(1):192-200. View

11.

Suzuki K, Tomita T, Ogra Y, Ohmichi M . Glutathione-conjugated arsenics in the potential hepato-enteric circulation in rats. Chem Res Toxicol. 2001; 14(12):1604-11. DOI: 10.1021/tx0155496. View

12.

Cohen S, Arnold L, Uzvolgyi E, Cano M, St John M, Yamamoto S . Possible role of dimethylarsinous acid in dimethylarsinic acid-induced urothelial toxicity and regeneration in the rat. Chem Res Toxicol. 2002; 15(9):1150-7. DOI: 10.1021/tx020026z. View

13.

Garcia-Vargas G, Del Razo L, Cebrian M, Albores A, Ostrosky-Wegman P, Montero R . Altered urinary porphyrin excretion in a human population chronically exposed to arsenic in Mexico. Hum Exp Toxicol. 1994; 13(12):839-47. DOI: 10.1177/096032719401301204. View

14.

SHIOBARA Y, Ogra Y, Suzuki K . Animal species difference in the uptake of dimethylarsinous acid (DMA(III)) by red blood cells. Chem Res Toxicol. 2001; 14(10):1446-52. DOI: 10.1021/tx015537k. View

15.

Styblo M, Del Razo L, Vega L, Germolec D, LeCluyse E, Hamilton G . Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells. Arch Toxicol. 2000; 74(6):289-99. DOI: 10.1007/s002040000134. View

16.

Armienta M, Rodriguez R, Cruz O . Arsenic content in hair of people exposed to natural arsenic polluted groundwater at Zimapán, México. Bull Environ Contam Toxicol. 1997; 59(4):583-9. DOI: 10.1007/s001289900519. View

17.

Del Razo L, Garcia-Vargas G, Vargas H, Albores A, Gonsebatt M, Montero R . Altered profile of urinary arsenic metabolites in adults with chronic arsenicism. A pilot study. Arch Toxicol. 1997; 71(4):211-7. DOI: 10.1007/s002040050378. View

18.

Del Razo L, Styblo M, Cullen W, Thomas D . Determination of trivalent methylated arsenicals in biological matrices. Toxicol Appl Pharmacol. 2001; 174(3):282-93. DOI: 10.1006/taap.2001.9226. View

19.

Yeh S . Skin cancer in chronic arsenicism. Hum Pathol. 1973; 4(4):469-85. DOI: 10.1016/s0046-8177(73)80060-7. View

20.

Styblo M, Drobna Z, Jaspers I, Lin S, Thomas D . The role of biomethylation in toxicity and carcinogenicity of arsenic: a research update. Environ Health Perspect. 2002; 110 Suppl 5:767-71. PMC: 1241242. DOI: 10.1289/ehp.110-1241242. View