Antivesicant Strategies Based on DNA Repair and Apoptosis

Abstract

DNA is a major cellular target of the vesicant chemical warfare agent sulfur mustard (SM, bis-(2-chloroethyl) sulfide). Others and we have proposed a possible role of apoptosis in SM vesication. Our results suggest that in SM-exposed human epidermal keratinicytes (HEK), DNA damage, DNA repair, and apoptosis may be interdependent. In HEK, SM causes cell death accompanied by caspase-3 activation indicating apoptosis. The general caspase inhibitor A-VAD-FMK (benzyl oxycarbonly-Val-Ala (o-methyl-fluromethylketone)) decreases not only SM induced apoptosis, but also protease stimulation consequent degradation of laminin-5 which maintains epidermal-dermal junction integrity. This knowledge may, therefore, be useful in developing successful antivesicant strategies.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2005
Accession Number
ADA449699

Entities

People

  • B. J. Benton
  • D. R. Anderson
  • D. S. Rosenthal
  • J. P. Petrali
  • K. R. Bhat
  • Patrick Ray
  • R. Ray
  • T. Hamilton
  • W. Holmes
  • W. J. Smith

Organizations

  • United States Army Medical Research Institute of Chemical Defense

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Blood
  • Cell Physiological Processes
  • Cells
  • Chemical Warfare
  • Chemical Warfare Agents
  • Chemical Weapons
  • Cyanides
  • Degradation
  • Epithelial Cells
  • Epithelium
  • Inhibitors
  • Programmed Cell Death
  • Rodents
  • Terrorism
  • Vesicants
  • Warfare

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Geochemistry

Technology Areas

  • Biotechnology