2010
DOI: 10.1093/toxsci/kfq106
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Monomethylarsonous Acid Produces Irreversible Events Resulting in Malignant Transformation of a Human Bladder Cell Line Following 12 Weeks of Low-Level Exposure

Abstract: Arsenic is a known human bladder carcinogen; however, the mechanisms underlying arsenical-induced bladder carcinogenesis are not understood. Previous research has demonstrated that exposure of a nontumorigenic human urothelial cell line, UROtsa, to 50 nM monomethylarsonous acid (MMA(III)) for 52 weeks resulted in malignant transformation. To focus research on the early mechanistic events leading to MMA(III)-induced malignancy, the goal of this research was to resolve the critical period in which continuous MMA… Show more

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Cited by 47 publications
(53 citation statements)
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“…The Futscher group has been active in this field through a series of studies investigating exposure to arseniccontaining compounds. Their findings illustrate that arsenic promotes a broad, gradual, and lasting perturbation in DNA methylation patterns that contributes to arsenic-mediated carcinogenesis in urothelial cells (135,136,329). Collectively, these results strongly suggest that the direct perturbation of the iron loaded into epigenetic enzymes is a strong stimulus for the modification of cellular epigenetic status.…”
Section: Cyr and Domannmentioning
confidence: 84%
“…The Futscher group has been active in this field through a series of studies investigating exposure to arseniccontaining compounds. Their findings illustrate that arsenic promotes a broad, gradual, and lasting perturbation in DNA methylation patterns that contributes to arsenic-mediated carcinogenesis in urothelial cells (135,136,329). Collectively, these results strongly suggest that the direct perturbation of the iron loaded into epigenetic enzymes is a strong stimulus for the modification of cellular epigenetic status.…”
Section: Cyr and Domannmentioning
confidence: 84%
“…The work by Wnek and colleagues (2010) suggested that the observed phenotypic changes should coincide with perturbations in the transcriptional activity of the cells. Hyper-proliferation, morphological changes, acquisition of anchorage-independent growth in semi-solid media, and the formation of tumors in immuno-compromised mice all coincide with alterations in pathways associated with cancer progression (from Gene Ontology and SPIA-based analysis).…”
Section: Discussionmentioning
confidence: 99%
“…However, Wnek et al (2010) were able to observe these changes as early as 12 weeks of exposure, and this acquired phenotype was sustained even after withdrawal of MMA(III). Therefore, the documented biochemical effects from MMA(III) exposure in UROtsa, such as the induction of ROS, DNA damage, production of pro-inflammatory cytokines, activation of mitogenic signals, and the increase in proliferation rate, exemplifies the utility of the model in the study of arsenic carcinogenesis and the unique effects of MMA(III) on the biology of the urothelium (Eblin et al, 2008b; Wnek et al, 2009; Escudero-Lourdes et al, 2010).…”
Section: Introductionmentioning
confidence: 99%
“…Furthermore, human skin keratinocyte (HaCaT) cells have been malignantly transformed following chronic low-level arsenic exposure (Pi et al, 2008) and have aided in the study of the mechanisms of co-carcinogenic effects of arsenic and ultraviolet irradiation (Sun et al, 2011). Along similar lines, other groups have established and used target cell line relevant models of arsenical carcinogenesis such as transformed human urinary bladder cells (Eblin et al, 2007; Wnek et al, 2010; Escudero-Lourdes et al, 2012; Garrett et al, 2014) or other cell lines including bronchial epithelial cell lines (Stuecke et al, 2012; Xu, et al, 2013) to help better define carcinogenic mechanisms. These have all been a great aid in advancing our knowledge of the remarkable diversity of the toxic and carcinogenic actions of this metalloid.…”
Section: Introductionmentioning
confidence: 99%