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Environ Health Perspect. Jun 1996; 104(6): 620–628.
PMCID: PMC1469390
Research Article

Methylation study of a population environmentally exposed to arsenic in drinking water.

Abstract

Methylation is considered the detoxification pathway for inorganic arsenic (InAs), an established human carcinogen. Urinary speciation analysis is used to assess the distribution of metabolites [monomethylarsonate (MMA), dimethylarsinate (DMA), and unmethylated arsenic (InAs)], as indicators of methylation capacity. We conducted a large biomarker study in northern Chile of a population chronically exposed to high levels of arsenic in drinking water. We report the results of the methylation study, which focused on the effects of exposure and other variables on the percent InAs, MMA, DMA, and the ratio of MMA to DMA in urine. The study consisted of 122 people in a town with arsenic water levels around 600 micrograms/l and 98 participants in a neighboring town with arsenic levels in water of about 15 micrograms/l. The corresponding mean urinary arsenic levels were 580 micrograms/l and 60 micrograms/l, of which 18.4% and 14.9% were InAs, respectively. The main differences were found for MMA:DMA; exposure, smoking, and being male were associated with higher MMA:DMA, while longer residence, Atacameño ethnicity, and being female were associated with lower MMA:DMA. Together, these variables explained about 30% of the variability in MMA:DMA. Overall, there was no evidence of a threshold for methylation capacity, even at very high exposures, and the interindividual differences were within a much wider range than those attributed to the variables investigated. The differences in percent InAs were small and within the ranges of other studies of background exposure levels. The biological significance of MMA:DMA, which was more than 1.5 times greater in the exposed group, and its relationship to sex, length of exposure, and ethnicity need further investigation because its relevance to health risk is not clear.

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Selected References

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  • Bates MN, Smith AH, Hopenhayn-Rich C. Arsenic ingestion and internal cancers: a review. Am J Epidemiol. 1992 Mar 1;135(5):462–476. [PubMed]
  • Wu MM, Kuo TL, Hwang YH, Chen CJ. Dose-response relation between arsenic concentration in well water and mortality from cancers and vascular diseases. Am J Epidemiol. 1989 Dec;130(6):1123–1132. [PubMed]
  • Chen CJ, Chen CW, Wu MM, Kuo TL. Cancer potential in liver, lung, bladder and kidney due to ingested inorganic arsenic in drinking water. Br J Cancer. 1992 Nov;66(5):888–892. [PMC free article] [PubMed]
  • Smith AH, Hopenhayn-Rich C, Bates MN, Goeden HM, Hertz-Picciotto I, Duggan HM, Wood R, Kosnett MJ, Smith MT. Cancer risks from arsenic in drinking water. Environ Health Perspect. 1992 Jul;97:259–267. [PMC free article] [PubMed]
  • Carlson-Lynch H, Beck BD, Boardman PD. Arsenic risk assessment. Environ Health Perspect. 1994 Apr;102(4):354–356. [PMC free article] [PubMed]
  • Hewitt DJ, Millner GC, Nye AC, Simmons HF. Investigation of arsenic exposure from soil at a superfund site. Environ Res. 1995 Feb;68(2):73–81. [PubMed]
  • Tam GK, Charbonneau SM, Bryce F, Pomroy C, Sandi E. Metabolism of inorganic arsenic (74As) in humans following oral ingestion. Toxicol Appl Pharmacol. 1979 Sep 15;50(2):319–322. [PubMed]
  • Buchet JP, Lauwerys R, Roels H. Urinary excretion of inorganic arsenic and its metabolites after repeated ingestion of sodium metaarsenite by volunteers. Int Arch Occup Environ Health. 1981;48(2):111–118. [PubMed]
  • Hopenhayn-Rich C, Smith AH, Goeden HM. Human studies do not support the methylation threshold hypothesis for the toxicity of inorganic arsenic. Environ Res. 1993 Feb;60(2):161–177. [PubMed]
  • Warner ML, Moore LE, Smith MT, Kalman DA, Fanning E, Smith AH. Increased micronuclei in exfoliated bladder cells of individuals who chronically ingest arsenic-contaminated water in Nevada. Cancer Epidemiol Biomarkers Prev. 1994 Oct-Nov;3(7):583–590. [PubMed]
  • Beck BD, Boardman PD, Hook GC, Rudel RA, Slayton TM, Carlson-Lynch H. Response to Smith et al. Environ Health Perspect. 1995 Jan;103(1):15–17. [PMC free article]
  • Boeniger MF, Lowry LK, Rosenberg J. Interpretation of urine results used to assess chemical exposure with emphasis on creatinine adjustments: a review. Am Ind Hyg Assoc J. 1993 Oct;54(10):615–627. [PubMed]
  • Georis B, Cardenas A, Buchet JP, Lauwerys R. Inorganic arsenic methylation by rat tissue slices. Toxicology. 1990 Jul;63(1):73–84. [PubMed]
  • Thompson DJ. A chemical hypothesis for arsenic methylation in mammals. Chem Biol Interact. 1993 Sep;88(2-3):89–14. [PubMed]
  • Bell DA, Taylor JA, Paulson DF, Robertson CN, Mohler JL, Lucier GW. Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer. J Natl Cancer Inst. 1993 Jul 21;85(14):1159–1164. [PubMed]
  • Giralt M, Lafuente A, Pujol F, Mallol J. Enhanced glutathione S-transferase activity and glutathione content in human bladder cancer. Followup study: influence of smoking. J Urol. 1993 Jun;149(6):1452–1454. [PubMed]
  • Hirata M, Tanaka A, Hisanaga A, Ishinishi N. Effects of glutathione depletion on the acute nephrotoxic potential of arsenite and on arsenic metabolism in hamsters. Toxicol Appl Pharmacol. 1990 Dec;106(3):469–481. [PubMed]
  • Buchet JP, Lauwerys R. Study of factors influencing the in vivo methylation of inorganic arsenic in rats. Toxicol Appl Pharmacol. 1987 Oct;91(1):65–74. [PubMed]
  • Buchet JP, Lauwerys R. Role of thiols in the in-vitro methylation of inorganic arsenic by rat liver cytosol. Biochem Pharmacol. 1988 Aug 15;37(16):3149–3153. [PubMed]
  • Bogdan GM, Sampayo-Reyes A, Aposhian HV. Arsenic binding proteins of mammalian systems: I. Isolation of three arsenite-binding proteins of rabbit liver. Toxicology. 1994 Nov 11;93(2-3):175–193. [PubMed]
  • Gonsebatt ME, Vega L, Montero R, Garcia-Vargas G, Del Razo LM, Albores A, Cebrian ME, Ostrosky-Wegman P. Lymphocyte replicating ability in individuals exposed to arsenic via drinking water. Mutat Res. 1994 Oct-Dec;313(2-3):293–299. [PubMed]
  • Borgoño JM, Vicent P, Venturino H, Infante A. Arsenic in the drinking water of the city of Antofagasta: epidemiological and clinical study before and after the installation of a treatment plant. Environ Health Perspect. 1977 Aug;19:103–105. [PMC free article] [PubMed]
  • Tu SH, Shirachi DY. Cytotoxicity of inorganic and organic arsenics in cell culture. Proc West Pharmacol Soc. 1992;35:61–63. [PubMed]
  • Yamanaka K, Ohba H, Hasegawa A, Sawamura R, Okada S. Mutagenicity of dimethylated metabolites of inorganic arsenics. Chem Pharm Bull (Tokyo) 1989 Oct;37(10):2753–2756. [PubMed]
  • Endo G, Kuroda K, Okamoto A, Horiguchi S. Dimethylarsenic acid induces tetraploids in Chinese hamster cells. Bull Environ Contam Toxicol. 1992 Jan;48(1):131–137. [PubMed]
  • Weinshilboum R. Pharmacogenetics of methylation: relationship to drug metabolism. Clin Biochem. 1988 Aug;21(4):201–210. [PubMed]
  • Caporaso N, Landi MT, Vineis P. Relevance of metabolic polymorphisms to human carcinogenesis: evaluation of epidemiologic evidence. Pharmacogenetics. 1991 Oct;1(1):4–19. [PubMed]
  • Zhong S, Wyllie AH, Barnes D, Wolf CR, Spurr NK. Relationship between the GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis. 1993 Sep;14(9):1821–1824. [PubMed]

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