Skip to main content

Advertisement

Log in

Association of glutathione S-transferase Ω 1-1 polymorphisms (A140D and E208K) with the expression of interleukin-8 (IL-8), transforming growth factor beta (TGF-β), and apoptotic protease-activating factor 1 (Apaf-1) in humans chronically exposed to arsenic in drinking water

  • Inorganic compounds
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Human exposure to arsenicals is associated with inflammatory-related diseases including different kinds of cancer as well as non-cancerous diseases like neuro-degenerative diseases, atherosclerosis, hypertension, and diabetes. Interindividual susceptibility has been mainly addressed by evaluating the role of genetic polymorphism in metabolic enzymes in inorganic arsenic (iAs) metabolism. Glutathione S-transferase omega 1-1 (GSTO1-1), which had been associated with iAs metabolism, is also known to participate in inflammatory and apoptotic cellular responses. The polymorphism A140D of GSTO1-1 has been not only associated with distinct urinary profile of arsenic metabolites in populations chronically exposed to iAs in drinking water, but also with higher risk of childhood leukemia and lung disease in non-exposed populations, suggesting that GSTO1-1 involvement in other physiologic processes different from toxics metabolism could be more relevant than is thought. We evaluated the association of the presence of A140D and E208K polymorphisms of GSTO1-1 gene with the expression of genes codifying for proteins involved in the inflammatory and apoptotic response in a human population chronically exposed to iAs through drinking water. A140D polymorphism was associated with higher expression of genes codifying for IL-8 and Apaf-1 mainly in heterozygous individuals, while E208K was associated with higher expression of IL-8 and TGF-β gene, in both cases, the association was independently of iAs exposure level; however, the exposure to iAs increased slightly but significantly the influence of A140D and E208K polymorphisms on such genes expression. These results suggest an important role of GSTO1-1 in the inflammatory response and the apoptotic process and indicate that A140D and E208K polymorphisms could increase the risk of developing inflammatory and apoptosis-related diseases in As-exposed populations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aguirre-Bañuelos P, Escudero-Lourdes C, Sanchez-Peña LC, Del Razo LM, Perez-Urizar J (2008) Inorganic arsenic exposure affects pain behavior and inflammatory response in rat. Toxicol Appl Pharmacol 229:374–385

    Article  PubMed  Google Scholar 

  • Agusa T, Kunito T, Kubota R, Inoue S, Fujihara J, Minh TB, Ha NN, Tu NP, Trang PT, Chamnan C, Takeshita H, Iwata H, Tuyen BC, Viet PH, Tana TS, Tanabe S (2010) Exposure, metabolism, and health effects of arsenic in residents from arsenic-contaminated groundwater areas of Vietnam and Cambodia: a review. Rev Environ Health 25:193–220

    Article  PubMed  CAS  Google Scholar 

  • Apostolakis S, Vogiatzi K, Amanatidou V, Spandidos DA (2009) Interleukin 8 and cardiovascular disease. Cardiovasc Res 84:353–360

    Article  PubMed  CAS  Google Scholar 

  • Balkwill F (2003) Chemokine biology in cancer. Review. Semin Immunol 15:49–55

    Article  PubMed  CAS  Google Scholar 

  • Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Review. Lancet 357:539–545

    Article  PubMed  CAS  Google Scholar 

  • Beard NA, Wei L, Dulhunty AF (2009) Control of muscle ryanodine receptor calcium release channels by proteins in the sarcoplasmic reticulum lumen. Clin Exp Pharmacol Physiol 36:340–345

    Article  PubMed  CAS  Google Scholar 

  • Berglund M, Lindberg AL, Rahman M, Yunus M, Grandér M, Lönnerdal B, Vahter M (2011) Gender and age differences in mixed metal exposure and urinary excretion. Environ Res 111(8):1271–1279

    Article  PubMed  CAS  Google Scholar 

  • Black PC, Dinney CP (2007) Bladder cancer angiogenesis and metastasis–translation from murine model to clinical trial. Cancer Metastasis Rev 26:623–634

    Article  PubMed  Google Scholar 

  • Blobe GC, Schiemann WP, Lodish HF (2000) Role of transforming growth factor beta in human disease. N Engl J Med 342:1350–1358

    Article  PubMed  CAS  Google Scholar 

  • Board PG, Coggan M, Cappello J, Zhou H, Oakley AJ, Anders MW (2008) S-(4-Nitrophenacyl) glutathione is a specific substrate for glutathione transferase omega 1-1. Anal Biochem 374:25–30

    Article  PubMed  CAS  Google Scholar 

  • Bretz F, Hothorn T, Westfall PH (2011) Multiple comparisons using R. CRC Press, Boca Raton

    Google Scholar 

  • Bunderson M, Brooks DM, Walker DL, Rosenfeld ME, Coffin JD, Beall HD (2004) Arsenic exposure exacerbates atherosclerotic plaque formation and increases nitrotyrosine and leukotriene biosynthesis. Toxicol Appl Pharmacol 201:32–39

    Article  PubMed  CAS  Google Scholar 

  • Cáceres DD, Werlinger F, Orellana M, Jara M, Rocha R, Alvarado SA, Luis Q (2010) Polymorphism of glutathione S-transferase (GST) variants and its effect on distribution of urinary arsenic species in people exposed to low inorganic arsenic in tap water: an exploratory study. Arch Environ Occup Health 65:140–147

    Article  PubMed  Google Scholar 

  • Cain K (2003) Chemical-induced apoptosis: formation of the Apaf-1 apoptosome. Drug Metab Rev 35:337–363

    Article  PubMed  CAS  Google Scholar 

  • Caroppi P, Sinibaldi F, Fiorucci L, Santucci R (2009) Apoptosis and human diseases: mitochondrion damage and lethal role of released cytochrome C as proapoptotic protein. Curr Med Chem 16:4058–4065

    PubMed  CAS  Google Scholar 

  • Chen YC, Guo YL, Su HJ, Hsueh YM, Smith TJ, Ryan LM (2003a) Arsenic methylation and skin cancer risk in south-western Taiwan. J Occup Environ Med 45:241–248

    Article  PubMed  CAS  Google Scholar 

  • Chen YC, Su HJ, Guo YL, Hsueh YM, Smith TJ, Ryan LM (2003b) Arsenic methylation and bladder cancer risk in Taiwan. Cancer Causes Control 14:303–310

    Article  PubMed  Google Scholar 

  • Chikazawa M, Inoue K, Fukata S, Karashima T, Shuin T (2008) Expression of angiogenesis-related genes regulates different steps in the process of tumor growth and metastasis in human urothelial cell carcinoma of the urinary bladder. Pathobiology 75:335–345

    Article  PubMed  CAS  Google Scholar 

  • Dani SU (2010) Arsenic for the fool: an exponential connection. Sci Total Environ 408:1842–1846

    Article  PubMed  CAS  Google Scholar 

  • De Vizcaya-Ruiz A, Barbier O, Ruiz-Ramos R, Cebrian ME (2009) Biomarkers of oxidative stress and damage in human populations exposed to arsenic. Mutat Res 674:85–92

    PubMed  Google Scholar 

  • Del Razo LM, Arellano MA, Cebrián ME (1990) The oxidation states of arsenic in well-water from a chronic arsenicism area of northern Mexico. Environ Pollut 64:143–153

    Article  PubMed  Google Scholar 

  • Del Razo LM, Styblo M, Cullen WR, Thomas DJ (2001) Determination of trivalent methylated arsenicals in biological matrices. Toxicol Appl Pharmacol 174:282–293

    Article  PubMed  Google Scholar 

  • Drobná Z, Walton FS, Paul DS, Xing W, Thomas DJ, Stýblo M (2010) Metabolism of arsenic in human liver: the role of membrane transporters. Arch Toxicol 84:3–16

    Article  PubMed  Google Scholar 

  • Dulhunty A, Gage P, Curtis S, Chelvanayagam G, Board P (2001) The glutathione transferase structural family includes a nuclear chloride channel and a ryanodine receptor calcium release channel modulator. J Biol Chem 276:3319–3323

    Article  PubMed  CAS  Google Scholar 

  • Engel RR, Hopenhayn-Rich C, Receveur O, Smith AH (1994) Vascular effects of chronic arsenic exposure: a review. Epidemiol Rev 16:184–209

    PubMed  CAS  Google Scholar 

  • Escudero-Lourdes C, Medeiros MK, Cárdenas-González MC, Wnek SM, Gandolfi JA (2010) Low level exposure to monomethyl arsonous acid-induced the over-production of inflammation-related cytokines and the activation of cell signals associated with tumor progression in a urothelial cell model. Toxicol Appl Pharmacol 244:162–173

    Article  PubMed  CAS  Google Scholar 

  • Guha Mazumder DN (2008) Chronic arsenic toxicity & human health. Indian J Med Res 128:436–447

    PubMed  CAS  Google Scholar 

  • Gustafson B (2010) Adipose tissue, inflammation and atherosclerosis. J Atheroscler Thromb 17(4):332–341

    Article  PubMed  CAS  Google Scholar 

  • Huang C, Ke Q, Costa M, Shi X (2004) Molecular mechanisms of arsenic carcinogenesis. Mol Cell Biochem 255:57–66

    Article  PubMed  CAS  Google Scholar 

  • Jiang X, McDermott JR, Ajees AA, Rosen BP, Liu Z (2010) Trivalent arsenicals and glucose use different translocation pathways in mammalian GLUT1. Metallomics 2:211–219

    Article  PubMed  CAS  Google Scholar 

  • Kalman DA, Hughes J, van Belle G, Burbacher T, Bolgiano D, Coble K, Mottet NK, Polissar L (1990) The effect of variable environmental arsenic contamination on urinary concentrations of arsenic species. Environ Health Perspect 89:145–151

    Article  PubMed  CAS  Google Scholar 

  • Karagas MR, Tosteson TD, Morris JS, Demidenko E, Mott LA, Heaney J (2004) Incidence of transitional cell carcinoma of the bladder and arsenic exposure in New Hampshire. Cancer Causes Control 15:465–472

    Article  PubMed  Google Scholar 

  • Kile ML, Hoffman E, Hsueh YM, Afroz S, Quamruzzaman Q, Rahman M, Mahiuddin G, Ryan L, Christiani DC (2009) Variability in biomarkers of arsenic exposure and metabolism in adults over time. Environ Health Perspect 117:455–460

    PubMed  CAS  Google Scholar 

  • Kumagai Y, Sumi D (2007) Arsenic: signal transduction, transcription factor, and biotransformation involved in cellular response and toxicity. Annu Rev Pharmacol Toxicol 47:243–462

    Article  PubMed  CAS  Google Scholar 

  • Kurttio P, Komulainen H, Hakala E, Kahelin H, Pekkanen J (1998) Urinary excretion of arsenic species after exposure to arsenic present in drinking water. Arch Environ Contam Toxicol 34(3):297–305

    Article  PubMed  CAS  Google Scholar 

  • Laliberte RE, Perregaux DG, Hoth LR, Rosner PJ, Jordan CK, Peese KM, Eggler JF, Dombroski MA, Geoghegan KF, Gabel CA (2005) Glutathione s transferase omega 1-1 is a target of cytokine release inhibitory drug and may be responsible for their effect on interleukin 1 posttranslational processing. J Biol Chem 278:16567–16578

    Article  Google Scholar 

  • Lantz RC, Hays AM (2006) Role of oxidative stress in arsenic-induced toxicity. Drug Metab Rev 38:791–804

    Article  PubMed  CAS  Google Scholar 

  • Lemarie A, Morzadec C, Bourdonnay E, Fardel O, Vernhet L (2006) Human macrophages constitute targets for immunotoxic inorganic arsenic. J Immunol 177:3019–3027

    PubMed  CAS  Google Scholar 

  • Li YJ, Scott WK, Zhang L, Lin PI, Oliveira SA, Skelly T, Doraiswamy MP, Welsh-Bohmer KA, Martin ER, Haines JL, Pericak-Vance MA, Vance JM (2006) Revealing the role of glutathione S-transferase omega in age-at-onset of Alzheimer and Parkinson diseases. Neurobiol Aging 27:1087–1093

    Article  PubMed  CAS  Google Scholar 

  • Marahatta SB, Punyarit P, Bhudisawasdi V, Paupairoj A, Wongkham S, Petmitr S (2006) Polymorphism of glutathione-S-transferase omega gene and risk of cancer. Cancer Lett 236:276–281

    Article  PubMed  CAS  Google Scholar 

  • Marnell LL, Garcia-Vargas GG, Chowdhury UK, Zakharyan RA, Walsh B, Avram MD, Kopplin MJ, Cebrian ME, Silbergeld EK, Aposhian HV (2003) Polymorphisms in the human Monomethyl arsonic Acid (MMAV) reductase/hGSTO1 gene and changes in urinary arsenic profiles. Chem Res Toxicol 16:1507–1513

    Article  PubMed  CAS  Google Scholar 

  • Meliker JR, Wahl RL, Cameron LL, Nriagu JO (2007) Arsenic in drinking water and cerebrovascular disease, diabetes mellitus, and kidney disease in Michigan: a standardized mortality ratio analysis. Environ Health 6(4):1–11

    Google Scholar 

  • Méndez-Gómez J, García-Vargas GG, López-Carrillo L, Calderón-Aranda ES, Gómez A, Vera E, Valverde M, Cebrián ME, Rojas E (2008) Genotoxic effects of environmental exposure to arsenic and lead on children in region Lagunera, Mexico. Ann N Y Acad Sci 1140:358–367

    Article  PubMed  Google Scholar 

  • Mukherjee B, Salavaggione OE, Pelleymounter LL, Moon I, Eckloff BW, Schaid DJ, Wieben ED, Weinshilboum RM (2006) Glutathione S-transferase omega 1 and omega 2 pharmacogenomics. Drug Metab Dispos 7:1237–1246

    Article  Google Scholar 

  • Piaggi S, Raggi C, Corti A, Pitzalis E, Mascherpa MC, Saviozzi M, Pompella A, Casini AF (2010) Glutathione transferase omega 1-1 (GSTO1-1) plays an anti-apoptotic role in cell resistance to cisplatin toxicity. Carcinogenesis 31(5):804–811

    Article  PubMed  CAS  Google Scholar 

  • Pongstaporn W, Pakakasama S, Sanguansin S, Hongeng S, Petmitr S (2009) Polymorphism of glutathione S-Transferase Omega gene: association with risk of childhood acute lymphoblastic leukemia. J Cancer Res Clin Oncol 135:673–678

    Article  PubMed  CAS  Google Scholar 

  • Rahman MM, Ng JC, Naidu R (2009) Chronic exposure of arsenic via drinking water and its adverse health impacts on humans. Environ Geochem Health Suppl 1:189–200

    Article  Google Scholar 

  • Sampayo-Reyes A, Hernández A, El-Yamani N, López-Campos C, Mayet-Machado E, Rincón-Castañeda CB, Limones-Aguilar Mde L, López-Campos JE, de León MB, González-Hernández S, Hinojosa-Garza D, Marcos R (2010) Arsenic induces DNA damage in environmentally exposed Mexican children and adults. Influence of GSTO1 and AS3MT polymorphisms. Toxicol Sci 117(1):63–71

    Google Scholar 

  • Schläwicke Engström K, Broberg K, Concha G, Nermell B, Warholm M, Vahter M (2007) Genetic polymorphisms influencing arsenic metabolism: evidence from Argentina. Environ Health Perspect 115(4):599–605

    Article  PubMed  Google Scholar 

  • Shi H, Xianglin S, Ke J (2004) Oxidative mechanism of arsenic toxicity and carcinogenesis. Mol Cell Biochem 255:67–78

    Article  PubMed  CAS  Google Scholar 

  • Siegel PM, Massague J (2003) Cytostatic and apoptotic actions of TGF-βeta in homeostasis and cancer. Nat Rev Cancer 3:807–821

    Article  PubMed  CAS  Google Scholar 

  • Simeonova PP, Hulderman T, Harki D, Luster MI (2003) Arsenic exposure accelerates atherogenesis in apolipoprotein E(−/−) mice. Environ Health Perspect 111(14):1744–1748

    Article  PubMed  CAS  Google Scholar 

  • Tanaka-Kagawa T, Jinno H, Hasegawa T, Makino Y, Seko Y, Hanioka N, Ando M (2003) Functional characterization of two variant human GSTO 1-1 s (Ala140Asp and Thr217Asn). Biochem Biophys Res Commun 301:516–520

    Article  PubMed  CAS  Google Scholar 

  • Thomas DJ (2007) Molecular processes in cellular arsenic metabolism. Toxicol Appl Pharmacol 222(3):365–373

    Google Scholar 

  • Trouba KJ, Germolec DR (2004) Micromolar concentrations of sodium arsenite induce cyclooxygenase-2 expression and stimulate p42/44 mitogen-activated protein kinase phosphorylation in normal human epidermal keratinocytes. Toxicol Sci 79(2):248–257

    Article  PubMed  CAS  Google Scholar 

  • Tseng CH (2008) Arsenic exposure and diabetes mellitus in the United States. JAMA 300(23):2728

    Google Scholar 

  • Tseng CH (2009) A review on environmental factors regulating arsenic methylation in humans. Toxicol Appl Pharmacol 235(3):338–350

    Article  PubMed  CAS  Google Scholar 

  • Tseng CH, Huang YK, Huang YL, Chung CJ, Yang MH, Chen CJ, Hsueh YM (2005) Arsenic exposure, urinary arsenic speciation, and peripheral vascular disease in blackfoot disease-hyperendemic villages in Taiwan. Toxicol Appl Pharmacol 206(3):299–308. Erratum in: Toxicol Appl Pharmacol. 2006 Mar 1;211(2):175

    Google Scholar 

  • Wang XJ, Sun Z, Chen W, Eblin KE, Gandolfi JA, Zhang DD (2007) Nrf2 protects human bladder urothelial cells from arsenite and monomethylarsonous acid toxicity. Toxicol Appl Pharmacol 225:206–213

    Article  PubMed  CAS  Google Scholar 

  • Waugh DJ, Wilson C (2008) The interleukin-8 pathway in cancer. Clin Cancer Res 14(21):6735–6741

    Article  PubMed  CAS  Google Scholar 

  • Wnek SM, Medeiros MK, Eblin KE, Gandolfi AJ (2009) Persistence of DNA damage following exposure of human bladder cells to chronic monomethylarsonous acid. Toxicol Appl Pharmacol 241(2):202–209

    Article  PubMed  CAS  Google Scholar 

  • Wu J, Liu J, Waalkes MP, Cheng ML, Li L, Li CX, Yang Q (2008) High dietary fat exacerbates arsenic-induced liver fibrosis in mice. Exp Biol Med (Maywood) 233(3):377–384

    Article  CAS  Google Scholar 

  • Xi S, Jin Y, Lv X, Sun G (2010) Distribution and speciation of arsenic by transplacental and early life exposure to inorganic arsenic in offspring rats. Biol Trace Elem Res 134(1):84–97

    Article  PubMed  CAS  Google Scholar 

  • Xie K (2001) Interleukin-8 and human cancer biology. Cytokine Growth Factor Rev 12(4):375–391

    Article  PubMed  CAS  Google Scholar 

  • Yanbaeva DG, Wouters EF, Dentener MA, Spruit MA, Reynaert NL (2009) Association of glutathione-S-transferase omega haplotypes with susceptibility to chronic obstructive pulmonary disease. Free Radic Res 43(8):738–743

    Article  PubMed  CAS  Google Scholar 

  • Yu L, Kalla K, Guthrie E, Vidrine A, Klimecki WT (2003) Genetic variation in genes associated with arsenic metabolism glutathione S transferase Omega 1-1 and purine nucleoside phosphorylase polymorphisms in European and indigenous Americans. Environ Health Perspect 111:1421–1427

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by SEP-CONACYT grant M-44051 to Claudia Escudero-Lourdes. Diana M Escobar received a partial scholarship through this grant. We thank Maggie Brunner, M.A., for reviewing the English translation.

Conflict of interest

The authors have no conflict of interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Claudia Escudero-Lourdes.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Escobar-García, D.M., Del Razo, L.M., Sanchez-Peña, L.C. et al. Association of glutathione S-transferase Ω 1-1 polymorphisms (A140D and E208K) with the expression of interleukin-8 (IL-8), transforming growth factor beta (TGF-β), and apoptotic protease-activating factor 1 (Apaf-1) in humans chronically exposed to arsenic in drinking water. Arch Toxicol 86, 857–868 (2012). https://doi.org/10.1007/s00204-012-0802-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-012-0802-x

Keywords

Navigation