APOPTOSIS OVERVIEW EMPHASIZING THE ROLE OF OXIDATIVE STRESS, DNA-DAMAGE AND SIGNAL-TRANSDUCTION PATHWAYS

Apoptosis (programmed cell death) is a central protective response to excess oxidative damage (especially DNA damage), and is also essential to embryogenesis, morphogenesis and normal immune function. An understanding of the cellular events leading to apoptosis is important for the design of new chemotherapeutic agents directed against the types of leukemias and lymphomas that are resistant to currently used chemotherapeutic protocols. We present here a review of the characteristic features of apoptosis, the cell types and situations in which it occurs, the types of oxidative stress that induce apoptosis, the signal-transduction pathways that either induce or prevent apoptosis, the biologic significance of apoptosis, the role of apoptosis in cancer, and an evaluation of the methodologies used to identify apoptotic cells. Two accompanying articles, demonstrating classic apoptosis(1) and non-classic apoptosis(2) in the same Epstein-Barr virus-transformed lymphoid cell line, are used to illustrate the value of employing multiple criteria to determine the type of cell death occurring in a given experimental system. Aspects of apoptosis and programmed cell death that are not covered in this review include histochemistry, details of cell deletion processes in the sculpting of tissues and organs in embryogenesis and morphogenesis, and the specific pathways leading to apoptosis in specific cell types. The readers should refer to the excellent books(3-9) and reviews(10-43) on the morphology, biochemistry and molecular biology of apoptosis already published on these topics. Emphasis is placed, in this review, on a proposed common pathway of apoptosis that may be relevant to all cell types.