APOPTOSIS - MOLECULAR CONTROL POINT IN TOXICITY

Apoptosis is a controlled form of cell death that serves as a molecula r point of regulation for biological processes. Cell selection by apop tosis occurs during normal physiological functions as well as toxiciti es and diseases. Apoptosis is the counterpart and counterbalance to mi tosis in cell population determination. Complex patterns of cell signa ling and specific gene expression are clearly involved in the control of cell fate. Exposure to an apogen, a trigger of apoptosis, can signi ficantly increase apoptotic cell loss during homeostatic processes as well as acute or chronic toxicities. Alternately, suppression of apopt osis through, for example, interference in cell signaling can result i n pathological accumulation of aberrant cells and diseases such as tum ors. Investigations into the mechanisms underlying apoptosis have exte nded into many areas, driven by increasingly sophisticated instrumenta l and molecular biology techniques. This symposium summary explores re lated aspects of apoptosis, including control of cell population size and function, specific gene activity and regulation, chromatin condens ation and scaffold detachment, oxidative stress-induced cell prolifera tion versus death by apoptosis or necrosis, and hepatotoxicant-induced apoptosis versus necrosis. Insights into the mechanisms governing apo ptosis and increasing appreciation of the relevance of apoptotic cell death are redirecting research in toxicology and carcinogenesis and ar e yielding novel therapeutic approaches for the control of toxicity, d isease, and ultimately perhaps senescence. (C) 1994 Academic Press, In c.