title: Transcriptional Modulation of the ERK1/2 MAPK and NF-κB Pathways in Human Urothelial Cells After Trivalent Arsenical Exposure: Implications for Urinary Bladder Cancer.
abstract: Chronic exposure to drinking water contaminated with inorganic arsenic (iAs) is associated with an increased risk of urinary bladder (UB) cancers in humans. The exact role of specific iAs metabolite(s) in As-mediated carcinogenesis remains largely unknown. Experimental evidence suggests that trivalent arsenicals, namely arsenite (iAsIII) and two of its metabolites, monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMAIII), are possible proximate UB carcinogens. Here, we used a transcriptomics approach to examine perturbed molecular pathways in a human urothelial cell line (UROtsa) after short-term exposure to iAsIII, MMAIIIand DMAIII. Molecular pathways containing genes that encode proteins implicated in UB cancer development were perturbed by both MMAIIIand DMAIII. These pathways included those of the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (ERK 1/2 MAPK) and nuclear factor kappa beta (NF-κB). Together, these results may inform the current understanding of effects in the UB induced by acute As exposure and the relationship of these effects with As-mediated carcinogenesis.
authors.affiliation: Department of Environmental Sciences and Engineering, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, NC 27599, USA.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Bailey
authors.forename: Kathleen
authors.initials: K
authors.lastname: Wallace
authors.forename: Lisa
authors.initials: L
authors.lastname: Smeester
authors.forename: Sheau-Fung
authors.initials: SF
authors.lastname: Thai
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Wolf
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Edwards
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fry
keywords: Arsenite; DMAIII; MMAIII; UROtsa; dimethylarsinous acid; extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase; gene expression; inflammation; microarray; monomethylarsonous acid; nuclear factor kappa beta; urinary bladder cancer