Accession Number : ADA375640


Title :   DNA Damage Induced Neuronal Death


Descriptive Note : Annual rept. 1 Sep 1998-1 Sep 1999


Corporate Author : OREGON UNIV HEALTH SCIENCES CENTER PORTLAND


Personal Author(s) : Kisby, Glen


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a375640.pdf


Report Date : OCT 1999


Pagination or Media Count : 13


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.


Descriptors :   *CHEMICAL WARFARE AGENTS , *NEUROTOXINS , MOLECULES , TOXICITY , DEOXYRIBONUCLEIC ACIDS , NERVE CELLS , CYTOTOXINS , MICE , CELLS(BIOLOGY) , CULTURES(BIOLOGY) , NITROGEN MUSTARDS , ASTROCYTES.


Subject Categories : TOXICOLOGY
      CHEMICAL, BIOLOGICAL AND RADIOLOGICAL WARFARE


Distribution Statement : APPROVED FOR PUBLIC RELEASE