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2895053 
Technical Report 
Key Involvement of Poly(ADP-ribosyl)ation in Defense Against Toxic Agents: Molecular Biology Studies 
Smulson, M 
2004 
NTIS/02931057 
GRA and I 
GRA and I 
We observed that exposure of rat lung alveolar type II epithelial cells (RLE-6TN) to JP-8 in vitro induces biochemical and morphological markers of apoptotic cell death such as activation of caspase-3, cleavage of poly(ADP- ribose) polymerase, chromatin condensation, release of cytochrome c from mitochondria, and cleavage of genomic DNA. Generation of reactive oxygen species (ROS) and depletion of intracellular reduced glutathione (GSH) also showed to play important roles in the induction of programmed cell death by JP-8. With the use of macroarray analysis, we further demonstrated that human Jurkat T cells exposed to JP-8 manifested pronounced changes in the expression of genes related to the cellular response to oxidative stress or to apoptosis. In contrast, similar analysis with normal human keratinocytes revealed that exposure to JP-8 induced changes in the expression of genes whose products function in detoxification or regulation of cell growth These findings might be relevant to the relative resistance of keratinocytes to JP-8 toxicity and support the notion that the induction of cell death by JP-8 may be cell type specific.