Cell Death by Apoptosis: Morphological, Genetic and Biochemical Features and Toxicological Implications

Abstract

Apoptosis is a type of cell death that plays an important role in early development and growth of normal adult tissue. It is regulated by physiological stimuli and is present in many species and tissues.Originally described as a “shrinkage necrosis” (Kerr, 1971) apoptosis is characterized by a marked reduction in cell volume and an increase in buoyant density (Ohyama et al., 1981 and Wyllie et al., 1982). Apoptotic bodies are characterized by their small size, dense cromatin, nuclear fragmentation, randomly assorted organelles in the cytoplasm, loss of characteristic membrane architecture and appareance of blebbing (Wyllie, 1980 et al.; Kyprianou et al., 1989). Significant alterations in membrane composition take place. The best-defined biochemical event in apoptosis involves nuclear DNA and the internucleosomal DNA fragmentation, probably caused by the activation of one or more endonucleases or DNA fragmenting enzymes (Wyllie, 1980b; Arends et al., 1990). Apoptosis is associated with death of isolated cells, rather than contiguous patches or areas of tissue; there is no inflammatory infiltrate; nuclear shrinkage occurs relatively early, but changes to the organelles and loss of membrane integrity are relatively late; the dying cells are phagocytosed by neighbouring cells, rather than immigrant professional phagocyte, the DNA is rapidly broken down (Kerr et al., 1972; Wyllie et al., 1980).