Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Global gene expression changes in human urothelial cells exposed to low-level monomethylarsonous acid.

Authors: Medeiros, Matthew; Zheng, Xinghui; Novak, Petr; Wnek, Shawn M; Chyan, Vivian; Escudero-Lourdes, Claudia; Gandolfi, A Jay

Published In Toxicology, (2012 Jan 27)

Abstract: Bladder cancer has been associated with chronic arsenic exposure. Monomethylarsonous acid [MMA(III)] is a metabolite of inorganic arsenic and has been shown to transform an immortalized urothelial cell line (UROtsa) at concentrations 20-fold less than arsenite. MMA(III) was used as a model arsenical to examine the mechanisms of arsenical-induced transformation of urothelium. A microarray analysis was performed to assess the transcriptional changes in UROtsa during the critical window of chronic 50nM MMA(III) exposure that leads to transformation at 3 months of exposure. The analysis revealed only minor changes in gene expression at 1 and 2 months of exposure, contrasting with substantial changes observed at 3 months of exposure. The gene expression changes at 3 months were analyzed showing distinct alterations in biological processes and pathways such as a response to oxidative stress, enhanced cell proliferation, anti-apoptosis, MAPK signaling, as well as inflammation. Twelve genes selected as markers of these particular biological processes were used to validate the microarray and these genes showed a time-dependent changes at 1 and 2 months of exposure, with the most substantial changes occurring at 3 months of exposure. These results indicate that there is a strong association between the acquired phenotypic changes that occur with chronic MMA(III) exposure and the observed gene expression patterns that are indicative of a malignant transformation. Although the substantial changes that occur at 3 months of exposure may be a consequence of transformation, there are common occurrences of altered biological processes between the first 2 months of exposure and the third, which may be pivotal in driving transformation.

PubMed ID: 22108045 Exiting the NIEHS site

MeSH Terms: Apoptosis Regulatory Proteins/biosynthesis; Apoptosis Regulatory Proteins/genetics; Biomarkers, Tumor/metabolism; Cell Proliferation/drug effects; Cell Transformation, Neoplastic/drug effects; Cells, Cultured; DNA Repair; Extracellular Matrix/metabolism; Gene Expression Profiling; Gene Expression/drug effects; Humans; Inflammation/chemically induced; Inflammation/metabolism; Mitogen-Activated Protein Kinases/genetics; Mitogen-Activated Protein Kinases/metabolism; Organometallic Compounds/toxicity*; Oxidative Stress/drug effects; Protein Array Analysis; Real-Time Polymerase Chain Reaction; Signal Transduction/drug effects; Signal Transduction/genetics; Urinary Bladder Neoplasms/chemically induced; Urinary Bladder Neoplasms/metabolism; Urothelium/cytology; Urothelium/drug effects*; Urothelium/metabolism*

Back
to Top