Exposure to lead is a significant environmental hazard facing children today. While the behavioral deficits due to lead exposure are known, the mechanisms that produce such permanent damage are not well understood. The underlying hypothesis of this research is based on the concept that long term adverse effects in cognitive processing, due to developmental exposure to lead, involve some alterations of gene function. Recent work in our lab has demonstrated that both transient and permanent alterations in cerebral mRNA levels occur in rats that are exposed to lead. This proposal seeks to elucidate the mechanisms through which lead may alter the regulation of gene expression. To accomplish this objective, both in vivo and in vitro models have been designed to examine the relationship between lead exposure and zinc finger transcription factors, which play key roles during growth and differentiation. These metalloproteins which regulate gene expression are likely targets for lead's action. The major aims of this work are to study the effects of lead exposure on the DNA binding properties of zinc finger proteins (zif268, SP1, and krox20) and to examine if their functional capacity of gene activation/deactivation is impaired by lead. Molecular techniques such as gel mobility shift assays, Northern and Western blotting, and tissue culture will be utilized in these studies. Understanding the mechanism of lead neurotoxicity with the models and experiments hitherto proposed will shed more light on metal toxicity and broaden our knowledge of the impact of heavy metals in the environment on our health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29ES008104-04
Application #
6164614
Study Section
Special Emphasis Panel (ZRG4-ALTX-3 (01))
Program Officer
Lawler, Cindy P
Project Start
1998-03-01
Project End
2003-02-28
Budget Start
2000-03-01
Budget End
2001-02-28
Support Year
4
Fiscal Year
2000
Total Cost
$125,315
Indirect Cost
Name
University of Rhode Island
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
135531015
City
Kingston
State
RI
Country
United States
Zip Code
02881