DNA Damage Induced Neuronal Death

Abstract

Experiments are proposed to examine the molecular mechanism by which mustard chemical warfare agents induce neuronal cell death. DNA damage is the proposed underlying mechanism of mustard-induced neuronal cell death. We propose a novel research strategy to test this hypothesis by using mice with perturbed DNA repair to explore the relationship between mustard-induced DNA damage and neuronal cell death. Initial in vitro studies (Years 1, 2 & 3) are proposed to examine the cytotoxic and DNA damaging properties of the sulfur mustard analogue mechlorethamine (nitrogen mustard or HN2) and the neurotoxic DNA-damaging agent methylazoxymethanol (MAM) using neuronal and astrocyte cell cultures from different brain regions of mice with perturbed DNA repair. Findings from these studies will be used to examine the in vivo neurotoxic effects of HN2 and MAM (Years 3 & 4) in mice with perturbed DNA repair.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 1999
Accession Number
ADA375640

Entities

People

  • Glen Kisby

Organizations

  • Oregon Health & Science University

Tags

DTIC Thesaurus Topics

  • Animals
  • Astrocytes
  • Brain
  • Cell Physiological Processes
  • Cells
  • Chemical Warfare
  • Chemical Warfare Agents
  • Chemical Weapons
  • Contrast
  • Culture Media
  • Culture Techniques
  • Genotypes
  • Laboratory Animals
  • Materials
  • Nervous System
  • Neurons
  • Nitrogen Mustards

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Geochemistry
  • Molecular Genetics

Technology Areas

  • Biotechnology