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Characterization of the Cellular Stress Response Induced by Exposure to Organic Compounds.
Final rept. 15 Jun 94-14 Sep 97,
CALIFORNIA STATE UNIV LONG BEACH
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Experiments were conducted for this project to determine if various characteristics of the cellular stress response among tissues could serve as the basis for developing a suite of biomarkers that 1 identify vulnerable target tissues 2 delineate the cellular manifestations of toxicity and 3 screen for exposure to specific classes of organic contaminants. Relationships were examined, at the cellular level, between accumulation and localization of stress proteins stress-7O, chaperonin6O, and ubiquitin and alterations in subcellular compartments using organic compounds with well characterized proteotoxic and genotoxic effects. These. objectives were accomplished using the following strategies 1. Well characterized toxins were used to test the hypothesis that the induction andor subcellular localization of stress-7O, and chaperonin, and ubiquitin, reflects the intercellular sites of toxicity of compounds with established mechanisms of toxicity 2. Induction and subcellular localization of stress-7O, chaperonin, and ubiquitin by novel compounds were compared with the cellular manifestations of toxicity, 3. The pattern of accumulation of stress proteins, as a result of exposure to these novel compounds, was characterized 4. Determined if the above compounds results in unique tissue and subcellular patterns of stress protein accumulation 5. Determined is the tissue and subcellular patterns of stress protein accumulation could be used as signatures to distinguish compounds or classes of compounds from one another.
APPROVED FOR PUBLIC RELEASE