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Project Publications: University of Arizona: Critical Events in the Transformation of Human Bladder Cells by Low-Level Arsenic Exposure

Superfund Research Program

Critical Events in the Transformation of Human Bladder Cells by Low-Level Arsenic Exposure

Project Leader: A. Jay Gandolfi
Grant Number: P42ES004940
Funding Period: 2000-2015
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  • Lopez-Carillo L, Gamboa-Loira B, Gandolfi A, Cebrian ME. 2020. Inorganic arsenic methylation capacity and breast cancer by immunohistochemical subtypes in northern Mexican women. Environ Res 184:doi:10.1016/j.envres.2020.109361 PMID:32209496


  • Garcia-Rico L, Meza-Figueroa D, Gandolfi A, del Rivero CI, Martinez-Cinco MA, Meza-Montenegro MM. 2018. Health risk assessment and urinary excretion of children exposed to arsenic through drinking water and soils in Sonora, Mexico. Biol Trace Elem Res doi:10.1007/s12011-018-1347-5 PMID:29721859


  • Oliva-Gonzalez C, Uresti-Rivera E, Galicia-Cruz O, Jasso-Robles F, Gandolfi A, Escudero-Lourdes C. 2017. The tumor suppressor phosphatase and tensin homolog protein (PTEN) is negatively regulated by NF-kappa b p50 homodimers and involves histone 3 methylation/deacetylation in UROtsa cells chronically exposed to monomethylarsonous acid. Toxicol Lett 280:92-98. doi:10.1016/j.toxlet.2017.08.013 PMID:28823542


  • Lopez-Carrillo L, Gamboa-Loira B, Becerra W, Hernandez-Alcaraz C, Hernandez-Ramirez RU, Gandolfi A, Franco-Marina F, Cebrian ME. 2016. Dietary micronutrient intake and its relationship with arsenic metabolism in Mexican women. Environ Res 151:445-450. doi:10.1016/j.envres.2016.08.015 PMID:27565879
  • Recio-Vega R, Gonzalez-Cortes, Olivas-Calderon E, Gandolfi A, Michel-Ramirez G, Lantz RC. 2016. Association between polymorphisms in arsenic metabolism genes and urinary arsenic methylation profiles in girls and boys chronically exposed to arsenic. Environ Mol Mutagen 57(7):516-525. doi:10.1002/em.22026 PMID:27327299 PMCID:PMC4980171


  • Lothrop N, Wilkinson S, Verhougstraete M, Sugeng AJ, Loh M, Klimecki WT, Beamer P. 2015. Home water treatment habits and effectiveness in a rural Arizona community. Water (Basel) 7(3):1217-1231. doi:10.3390/w7031217 PMID:26120482 PMCID:PMC4479291
  • Recio-Vega R, Gonzalez-Cortes, Olivas-Calderon E, Lantz RC, Gandolfi A, Gonzalez-De Alba C. 2015. In utero and early childhood exposure to arsenic decreases lung function in children. J Appl Toxicol 35(4):358-366. doi:10.1002/jat.3023 PMID:25131850 PMCID:PMC4750377


  • Beamer P, Sugeng AJ, Kelly MD, Lothrop N, Klimecki WT, Wilkinson S, Loh M. 2014. Use of dust fall filters as passive samplers for metal concentrations in air for communities near contaminated mine tailings. Environ Sci Process Impacts 16(6):1275-1281. doi:10.1039/c3em00626c PMID:24469149 PMCID:PMC4038653
  • Burchiel SW, Lauer FT, Beswick EJ, Gandolfi A, Parvez F, Liu K, Hudson LG. 2014. Differential susceptibility of human peripheral blood T cells to suppression by environmental levels of sodium arsenite and monomethylarsonous acid. PLoS One 9:8. doi:10.1371/journal.pone.0109192 PMID:25271956 PMCID:PMC4182801
  • Ezeh PC, Lauer FT, MacKenzie D, McClain S, Liu K, Hudson LG, Gandolfi A, Burchiel SW. 2014. Arsenite selectively inhibits mouse bone marrow lymphoid progenitor cell development in vivo and in vitro and suppresses humoral immunity in vivo. PLoS One 9(4):e93920. doi:10.1371/journal.pone.0093920 PMID:24714590 PMCID:PMC3979857
  • Medeiros MK, Le TM, Troup D, Novak P, Gandolfi A. 2014. Expression of selected pathway-marker genes in human urothelial cells exposed chronically to a non-cytotoxic concentration of monomethylarsonous acid. Toxicol Rep 1:421-434. doi:10.1016/j.toxrep.2014.07.004 PMID:25177542 PMCID:PMC4144464
  • Zhou X, Sun X, Mobarak C, Gandolfi A, Burchiel SW, Hudson LG, Liu K. 2014. Differential binding of monomethylarsonous acid compared to arsenite and arsenic trioxide with zinc finger peptides and proteins. Chem Res Toxicol 27(4):690-698. doi:10.1021/tx500022j PMID:24611629 PMCID:PMC3998772


  • Diaz-Villasenor A, Cruz L, Cebrian A, Hernandez-Ramirez RU, Hiriart M, Garcia-Vargas GG, Bassol S, Sordo M, Gandolfi A, Klimecki WT, Cebrian ME, Ostrosky-Wegman P, Lopez-Carillo L. 2013. Arsenic exposure and calpain-10 polymorphisms impair the function of pancreatic beta-cells in humans: A pilot study of risk factors for T2DM. PLoS One 8:doi:10.1371/journal.pone.0051642 PMID:23349674 PMCID:PMC3551951


  • Canet MJ, Hardwick RN, Lake AD, Kopplin MJ, Scheffer GL, Klimecki WT, Gandolfi A, Cherrington NJ. 2012. Altered arsenic disposition in experimental nonalcoholic fatty liver disease. Drug Metab Dispos 40(9):1817-1824. doi:10.1124/dmd.112.046177 PMID:22699396 PMCID:PMC3422539
  • Escudero-Lourdes C, Wu T, Camarillo JM, Gandolfi A. 2012. Interleukin-8 (IL-8) over-production and autocrine cell activation are key factors in monomethylarsonous acid MMA(III) -induced malignant transformation of urothelial cells. Toxicol Appl Pharmacol 258:10-18. doi:10.1016/j.taap.2011.10.002 PMID:22015448 PMCID:PMC3254786
  • Medeiros MK, Zheng XH, Novak P, Wnek SM, Chyan V, Escudero-Lourdes C, Gandolfi A. 2012. Global gene expression changes in human urothelial cells exposed to low-level monomethylarsonous acid. Toxicology 291:102-12. doi:10.1016/j.tox.2011.11.002 PMID:22108045 PMCID:PMC3245769


  • Wnek SM, Kuhlman CL, Camarillo JM, Medeiros MK, Liu KJ, Lau SS, Gandolfi A. 2011. Interdependent genotoxic mechanisms of monomethylarsonous acid: Role of ROS-induced DNA damage and poly(ADP-ribose) polymerase-1 inhibition in the malignant transformation of urothelial cells. Toxicol Appl Pharmacol 257:1-13. doi:10.1016/j.taap.2011.08.029 PMID:21925530 PMCID:PMC3220758


  • Escudero-Lourdes C, Medeiros MK, Cardenas-Gonzalez MC, Wnek SM, Gandolfi A. 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(2):162-173. doi:10.1016/j.taap.2009.12.029 PMID:20045430 PMCID:PMC2846965
  • Gomez-Rubio P, Meza-Montenegro MM, Cantu-Soto E, Klimecki WT. 2010. Genetic association between intronic variants in AS3MT and arsenic methylation efficiency is focused on a large linkage disequilibrium cluster in chromosome 10. J Appl Toxicol 30(3):260-270. doi:10.1002/jat.1492 PMID:20014157 PMCID:PMC2862143
  • Wnek SM, Jensen TJ, Severson PL, Futscher BW, Gandolfi A. 2010. Monomethylarsonous acid produces irreversible events resulting in malignant transformation of a human bladder cell line following 12 weeks of low-level exposure. Toxicol Sci 116(1):44-57. doi:10.1093/toxsci/kfq106 PMID:20375083 PMCID:PMC2886861



  • Eblin KE, Bredfeldt TG, Gandolfi A. 2008. Immortalized human urothelial cells as a model of arsenic-induced bladder cancer. Toxicology 248(2-3):67-76. doi:10.1016/j.tox.2008.03.020 PMID:18456381
  • Eblin KE, Hau AM, Jensen TJ, Gandolfi A, Futscher BW. 2008. The role of reactive oxygen species in arsenite and monomethylarsonous acid-induced signal transduction in human bladder cells: acute studies. Toxicology 250(1):47-54. doi:10.1016/j.tox.2008.05.018 PMID:18588940 PMCID:PMC2567114
  • Jensen TJ, Eblin KE, Gandolfi A, Novak P. 2008. Epigenetic remodeling during arsenical-induced malignant transformation. Carcinogenesis 29:1500-8. PMID:18448484
  • Meza MM, Kopplin MJ, Burgess JL, Gandolfi A. 2008. Urinary arsenic methylation profile in children exposed to low arsenic levels through drinking water. Toxicol Sci 90:957-970. doi:10.1080/02772240701782140


  • Eblin KE, Bredfeldt TG, Buffington SE, Gandolfi A. 2007. Mitogenic signal transduction caused by monomethylarsonous acid in human bladder cells: role in arsenic-induced carcinogenesis. Toxicol Sci 95(2):321-330. PMID:17093206
  • Meza MM, Gandolfi A, Klimecki WT. 2007. Developmental and genetic modulation of arsenic biotransformation: a gene by environment interaction?. Toxicol Appl Pharmacol 222(3):381-387. doi:10.1016/j.taap.2006.12.018 PMID:17306849 PMCID:PMC2040165
  • Wang X, Sun Z, Chen W, Eblin KE, Gandolfi A, Zhang DD. 2007. Nrf2 protects human bladder urothelial cells from arsenite and monomethylarsonous acid toxicity. Toxicol Appl Pharmacol 225(2):206-13. PMID:17765279


  • Bredfeldt TG, Jagadish B, Eblin KE, Mash EA, Gandolfi A. 2006. Monomethylarsonous acid induces transformation of human bladder cells. Toxicol Appl Pharmacol 216(1):69-79. PMID:16806342
  • Eblin KE, Bowen ME, Cromey DW, Bredfeldt TG, Mash EA, Lau SS, Gandolfi A. 2006. Arsenite and monomethylarsonous acid generate oxidative stress response in human bladder cell culture. Toxicol Appl Pharmacol 217(1):7-14. PMID:16930658
  • Groves CE, Suhre WB, Cherrington NJ, Wright S. 2006. Sex differences in the mRNA, protein, and functional expression of organic anion transporter (Oat) 1, Oat3, and organic cation transporter (Oct) 2 in rabbit renal proximal tubules. J Pharmacol Exp Ther 316(2):743-752. PMID:16249371
  • Peraza MA, Cromey DW, Carolus B, Carter DE, Gandolfi A. 2006. Morphological and functional alterations in human proximal tubular cell line induced by low level inorganic arsenic: evidence for targeting of mitochondria and initiated apoptosis. J Appl Toxicol 26(4):356-67. PMID:16773642


  • Billings KE, Bredfeldt TG, Zheng XH, Kopplin MJ, Watts GS, Sens DA, Mash EA, Gandolfi A. 2005. Characterization of human bladder urothelial cells malignantly transformed by arsenite. Environ Health Perspect 84(S1):31.
  • Bredfeldt TG, Billings KE, Zheng XH, Mash EA, Domann FE, Lau SS, Sens DA, Gandolfi A. 2005. Arsenite and monomethyl arsonous acid-induced toxicity ion human urothelial cells. Environ Health Perspect 84(S1):31.
  • Zheng XH, Bredfeldt TG, Watts GS, Gandolfi A. 2005. Toxicogenomical study on human bladder epithelium exposed to arsenic. Environ Health Perspect 84(S1):238.


  • Gandolfi A. 2003. In vitro techniques in screening and mechanistic studies: organ perfusion, slices, and nephron components. In: Toxicology and the Kidney - Third Edition.
  • Johnson PD, Goldberg SJ, Mays MZ, Dawson BV. 2003. Threshold of trichloroethylene contamination in maternal drinking waters affecting fetal heart development in the rat. Environ Health Perspect 111(3):289-292. PMID:12611656
  • Kirkpatrick DS, Dale KV, Catania JM, Gandolfi A. 2003. Low-level arsenite causes accumulation of ubiquitinated proteins in rabbit renal cortical slices and HEK 293 cells. Toxicol Appl Pharmacol 186(2):101-109. PMID:12639501
  • Kirkpatrick DS, Weldon SF, Tsaprailis G, Liebler DC, Gandolfi A. 2003. Qualitative and quantitative analysis of changes in the ubiquitin pathway in human cells using LC-MS/MS. Mol Cell Proteomics
  • Peraza MA, Carter DE, Gandolfi A. 2003. Toxicity and metabolism of subcytotoxic inorganic arsenic in human renal proximal tubule epithelial cells (HK-2). Cell Biol Toxicol 19(4):253-264. PMID:14686617
  • Zheng XH, Watts GS, Vaught S, Gandolfi A. 2003. Low-level arsenate induced gene expression in HEK 293 cells. Toxicology 187(1):39-48. PMID:12679051


  • Adams DG, Sachs NA, Vaillancourt RR. 2002. Phosphorylation of the stress-activated protein kinase, MEKK3, at serine 166. Arch Biochem Biophys 407(1):103-116. PMID:12392720
  • Dale KV, Liebler DC, Gandolfi A. 2002. Identification of ubiquitin-conjugated proteins using lc-ms techniques: potential molecular indicators of toxic insults. Environ Health Perspect 66:A1083.
  • Peraza MA, Kopplin MJ, Carter DE, Gandolfi A. 2002. Inorganic arsenic biotransformation and mitochondrial toxicity in HK-2 human proximal tubular cells. Environ Health Perspect 66:A403.
  • Sipes IG, McQueen CA, Gandolfi A. 2002. Inorganic arsenic biotransformation and mitochondrial toxicity in HK-2 human proximal tubular cells. In: Comprehensive Toxicology. Vol. 14, Cellular and Molecular Toxicology. Elsevier-Academic Press, pp.644.


  • Dale KV, Liebler DC, Gandolfi A. 2001. Identification of ubiquitin-conjugated proteins using lc-ms techniques: potential molecular indicators of toxic insults. In: Proceedings of the Symposium on Gene Expression, December 2-4. Bethesda, MD.
  • Gandolfi A. 2001. Hazardous Waste Risk and Remediation in the Southwest. In: Proceedings of the Superfund Basic Research Program Annual Meeting: Assessing Risks of Hormonally Active Agents, December 10-12, 2001. University of Florida Conference Center, Gainsville, FL.
  • Gandolfi A. 2001. Organ Perfusion, Slices and Nephron Components in Toxicology of the Kidney. In: In Vitro Techniques in Screening and Mechanistic Studies (3rd edition). Raven Press,
  • Wijeweera JB, Gandolfi A, Parrish AR, Lantz RC. 2001. Sodium arsenite enhances AP-1 and NFKB DNA binding and induces stress protein expression in precision-cut rat lung slices. Toxicol Sci 61(2):283-294. PMID:11353137


  • Catania JM, Gandolfi A. 2000. Increased ubiquitin-conjugated proteins following low-level arsenite exposure. In: Proceedings of the SEGH (Society for Environmental Geochemistry and Health) Fourth International Conference on Arsenic Exposure and Health Effects, June 18-22. San Diego, CA.
  • Zheng XH, Gandolfi A, Wilson CL, Parrish AR. 2000. Analysis of differential expressed genes in rabbit renal cortical slices exposed to arsenic compounds. In: Proceedings of the SEGH (Society for Environmental Geochemistry and Health) Fourth International Conference on Arsenic Exposure and Health Effects, June 18-22. San Diego, CA.
  • Zheng XH, Parrish AR, Gandolfi A. 2000. Analysis of differentially-expressed genes in rabbit renal cortical slices exposed to arsenic compounds. Southwest Environmental Health Sciences Center Newsletter
  • Zheng XH, Wilson CL, Parrish AR, Gandolfi A. 2000. Differential gene expression in rabbit renal cortical slices exposed to arsenic compounds. Toxicol Sci 54:


  • Parrish AR, Zheng XH, Turney KD, Younis HS, Gandolfi A. 1999. Enhanced transcription factor DNA binding and gene expression induced by arsenite or arsenate in renal slices. Toxicol Sci 50:98-105. PMID:10445758
  • Turney KD, Parrish AR, Gandolfi A. 1999. Selective activation in the MAPK pathway by Hg(II). Toxicol Sci 48:331.
  • Turney KD, Parrish AR, Orozco J, Gandolfi A. 1999. Selective activation in the MAPK pathway by Hg(II) in precision-cut rabbit renal cortical slices. Toxicol Appl Pharmacol 160(3):262-270. PMID:10544060


  • Turney KD, Parrish AR, Gandolfi A. 1998. Changes in AP-1 and c-jun expression in precision-cut rabbit renal cortical slices following exposure to Hg(II). Environ Health Perspect 31:380.
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