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Background
The human bladder is the most sensitive internal organ to arsenic-induced carcinogenesis. Yet, the mechanism(s) by which arsenic produces bladder cancer are unknown and the toxic effects of low-level arsenic exposure to produce bladder injury have not been adequately examined.
Goal
To find the critical events that low-level arsenical exposure causes in human bladder cell cultures resulting in their eventual transition into malignantly transformed cells.
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Image shows enhanced accumulation of ubiquinated proteins in UROtsa cells treated with BSO and exposed to As(III). B = BSO treated. |
Objectives
1. Demonstrate that low-level, short-term exposures to arsenicals react directly with proteins, signaling systems, or regulatory systems in human bladder cell cultures resulting in irreversible changes that may lead to malignant transformation.
2. Determine if low-level, short-term exposures to arsenicals generate reactive oxygen species in human bladder cell cultures which trigger protein, DNA, signaling, or regulatory changes resulting in irreversible alterations that may lead to malignant transformation.
3. Examine if low-level, short term exposures of primary cultures of human bladder cells to arsenicals produce similar alterations observed with the bladder cell cultures?
4. Determine if interactions of arsenicals with human bladder cells result in a biomarker of toxic insult that can be used to assess arsenical-induced bladder injury in populations exposed to arsenic.
Project 1 publications resulting
from research conducted under the Superfund Research Program
during the grant funding period of 2005 to present.
Contact
A. Jay Gandolfi
gandolfi@pharmacy.arizona.edu
(520) 626-6696
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