Development of Physiological Models to Study Stress Protein Responses

Multicellular animals are exposed routinely to oxidizing chemicals and radiation from the environment, as well as endogenous metabolic by-products that can damage DNA and proteins over the life-span of the cell. Such damage may contribute to tissue injury, promote aging, and is implicated in many chronic degenerative human diseases, including cancer. The interplay of environmental agents with factors that control mammalian cell integrity have been most widely studied by employing tumor cell lines as a convenient source of homogeneous and rapidly growing cells. Although it could be argued that the use of tumor cell lines precludes the formation of an accurate understanding of the mechanisms regulating the normal cellular damage response, the use of such cultured systems has facilitated the discovery of a host of regulatory enzymes and repair factors.