Lead toxicity in astrogila /

Toxic effects of low lead upon the developing nervous system remain a major health issue in this country. Among the unsolved problems are mechanisms of cellular injury, as well as mechanisms of Pb uptake, storage, and tolerance in brain cells that accumulate Pb. Although cell cultures are powerful...

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Bibliographic Details
Main Author: Legare, Marie Elise, 1956-
Format: Thesis Book
Language:English
Published: [Place of publication not identified] : [publisher not identified] ; 1995.
Subjects:
Online Access:http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=742145191&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD

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100 1 |a Legare, Marie Elise,  |d 1956- 
245 1 0 |a Lead toxicity in astrogila /  |c by Marie Elise Legare. 
264 1 |a [Place of publication not identified] :  |b [publisher not identified] ;  |c 1995. 
300 |a x, 102 leaves :  |b illustrations ;  |c 28 cm. 
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502 |b Ph. D.  |c Texas A&M University  |d 1995. 
500 |a "Major Subject: Veterinary Anatomy". 
530 |a Issued also on microfiche from University Microfilms Inc. 
520 |a Toxic effects of low lead upon the developing nervous system remain a major health issue in this country. Among the unsolved problems are mechanisms of cellular injury, as well as mechanisms of Pb uptake, storage, and tolerance in brain cells that accumulate Pb. Although cell cultures are powerful tools for investigating lead toxicity, most studies n vitro have characterized gross cytotoxic effects from massive Pb exposure, rather than the early, discrete biochemical changes that precede low exposure levels. We hypothesize a series of events through which a Pb-exposed cell progresses, beginning with selective changes as discrete as interfering with the metabolism of Ca" to ending with cell death or significantly impaired cell function. Between these endpoints lies a continuum of metabolic changes that multiply from the initial molecular injuries. Superimposed on this continuum are compensatory mechanisms that allow cells to adapt to intracellular Pb and correct molecular damage. Our studies will characterize events in the early part of the continuum. We will focus on the molecular changes that occur in one type of brain cell, astroglia, following exposure to low levels of Pb (0.1 to 1 [LM). Our first goal will be to identify highly sensitive molecular indicators of cell injury (toxic endpoints) with the focus on mechanism. Cellular Ca" is a likely common denominator in many reactions to Pb toxicity. Therefore we will evaluate low-level Pb exposure on 3 parameters related to Ca: (1) cellular glutathione, (2) mitochondrial membrane potential and (3) the regulation of gap junction permeability. Further studies will investigate the mechanisms of Pb uptake by astroglia. Interactive laser cytometry with microscopic image analysis will be exploited to develop highly sensitive assays for quantitating toxic endpoints. This approach will be combined with more traditional assays to obtain a broad coverage of molecular events transpiring in cells exposed to submicromolar Pb concentrations. 
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