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Background
The mechanism(s) by which arsenic produces bladder cancer are unknown. Additionally, the toxic effects of low-level arsenic exposure to produce bladder injury have not been adequately examined.


Goal
To clarify the toxic effects of low-level arsenic in a human bladder model and provide potential biomarkers for arsenic-induced bladder injury.

Photo:  Shows enhanced accumulationof ubiquinated proteins in UROtsa cells treated with BSO and exposed to As(III).
Image shows enhanced accumulation of ubiquinated proteins in UROtsa cells treated with BSO and exposed to As(III). B = BSO treated.
Objectives
1. Determine the role of biotransformation of arsenic in the bladder to produce sub-cytotoxic effects.

2. Determine if low-level arsenic exposure to the bladder is producing toxicity via proteotoxic mechanisms.

3. Determine if low-level arsenic exposure to the bladder produces toxicity via an oxidative stress mechanism.

4. Determine if low-level arsenic exposure to the bladder is affecting the ubiquitin pathway and its toxic consequences.

5. Using the above information, determine if biomarkers of arsenic-induced bladder injury are present in human bladder samples.

Contact
A. Jay Gandolfi
gandolfi@pharmacy.arizona.edu
(520) 626-6696
Molecular Effects of Low Level Arsenic on the Human Bladder

Superfund Basic Research Program
The University of Arizona
College of Pharmacy, Room 331
Tucson, Arizona 85721-0207
P: 520-626-7101
F: 520-626-2466

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Banner Photo Credit:
Janick F. Artiola

Funded in part by:

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