Altering genes that control cell division is recognized as the major cause of cancer. The initiation- or progression phase of carcinogenesis is caused by the inactivation or loss of certain tumour suppressor genes. Organochlorine compounds are persistent in the environment and heighten the risk of cancer among animals and humans. Most organochlorine chemicals have endocrine-disrupting properties that trigger the activation of stress response genes. Much of what is known about genomic and proteomic responses in mammalian cells is attained from cellular adjustment to deleterious forms of stress. It is believed that changes in gene expression can be linked to specific classes of toxic compounds with unique fingerprints that aid in characterizing various mechanisms of action. Identification of stress-response genes provides the necessary link between a stimulus from the external environment and the events that occur among intracellular components. The effort devoted to identifying stress-response genes as a response to environmental contaminants can be of extreme importance because stress-response genes can be used as potential biomarkers for monitoring organochlorine exposure. The functionality of stress-response genes is orchestrated by their own signaling mechanisms. Pentachlorophenol (PCP) is an organochlorine herbicide and prevalent wood preservative in the United States (U.S.). The biocidal action of PCP protects timber from fungal rot and wood-boring insects, thus extending the life of wood products. PCP is one of the most heavily used organochlorine pesticides in the U.S. preceded by the herbicides atrazine, and alachlor. Noticeable interest is drawn to PCP for its ability to induce systemic toxicity and carcinogenesis . This proposal focuses on the toxicity of PCP to the extent that it may alter gene expressions in hepatocyte culture. The goal to be reached by the end of this grant period is to identify stress-response genes that contribute to cell proliferation and programmed cell death in PCP-treated TIB-73 mouse hepatocytes. This project is driven by the hypothesis that that exposure to sublethal concentrations of PCP will cause the transcriptional activation of stress_response genes in our established in vitro TIB-73 mouse hepatocyte model system.