Molecular Effects of Low Level Exposure to Arsenic

Background
Chronic exposure to low-level arsenic frequently results in skin, lung, bladder, and kidney cancer. The role of inorganic arsenicals in regulating toxic effects from arsenic exposure is still unknown.

Tissue incubator.

Goal
To determine if inorganic arsenicals regulate specific genes and therefore specific proteins, and if the activity of those proteins is responsible for the toxic effects observed from low-level chronic exposure.

Objectives
1. Identify proteins that associate with a serine/threonine kinase involved in arsenic signaling.

2. Characterize the activity of proteins that are regulated by arsenic and correlate protein activity with cellular toxicity.

3. Identify specific genes whose expression pattern changes after low level exposure to inorganic arsenic.

4. Examine the expression of key genes induced by inorganic arsenic exposure and correlate gene expression with cellular injury.

Significant Findings
1. Arsenic effects the association of specific protein complexes in the signaling cascade.

2. Low-level arsenic causes the accumulation of protein debris which can cause a variety of cellular defects (e.g. cell cycling, differentiation, cancer).

3. Low-level arsenic effects specific gene expression responsible for stress response, oxidative stress, adhesion, and differentiation.

Publications

Contact
A. Jay Gandolfi
gandolfi@pharmacy.arizona.edu
520-626-6696