Molecular Effects of Low Level Arsenic on the Human Bladder

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.

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