Apoptosis: A Distinctive Mode of Cell Death that Plays an Opposite Role to Mitosis in Cell Population Kinetics

Abstract

SUMMARYThe term apoptosis has been coined for a morphologically distinctive mode of cell death, which plays an opposite role to mitosis in controlling the size of animal tissues: it is fundamentally different from the well known phenomenon of necrosis that results from irreversible injury to cells by agents such as toxins and ischaemia.Cells affected by apoptosis condense and bud to produce many membrane‐bounded fragments in which organelles are well preserved. These are phagocytosed and digested by nearby resident tissue cells without associated inflammation; the viable cells merely close ranks. Extensive deletion of cells may thus take place without disorganisation of overall tissue architecture.Apoptosis occurs continuously in healthy animals. It is enhanced in endocrine‐dependent tissues during the reversible shrinkage that follows appropriate hormone withdrawal or administration, and it is also implicated in total and irreversible involution of tissues in normal animals, such as loss of the tadpole tail during metamorphosis and elimination of phylogenetic vestiges during embryonic development.Apoptosis takes place spontaneously and continuously in malignant neoplasms, often grossly retarding their growth, and cytotoxic drug administration and X irradiation enhance apoptosis as well as inhibiting mitosis in neoplasms; tumour regression following therapy with these agents is the result of tipping the balance between the two processes. Hyperthermia enhances apoptosis in foetal tissues and adult seminiferous tubules; its effect on apoptosis in neoplasms needs study. Cell mediated immune attack on cells induces apoptosis, not necrosis; apoptosis may thus sometimes be enhanced in neoplasms by immunological means.The features of apoptosis suggest that it is an active process of cellular self‐destruction rather than a form of cell degeneration. This carries the implication that it is genetically programmed. Further understanding of the regulation of the onset of apoptosis at the molecular level may lead to the discovery of improved methods of tumour treatment.