Abstract

The maintenance of homeostasis in normal tissues reflects a balance between cell proliferation and cell death. Programmed cell death (Apoptosis) is the ubiquitous physiological phenomenon of intentional cell death that eliminates redundant cells, changes phenotypic composition during histogenesis, provides form during morphogenesis and balances mitosis in renewing tissues. This pathway of cell death is characterized by internucleosomal digestion of genomic DNA. Such DNA digestion can be induced by both physiological stimuli and cytotoxic treatment with many anticancer agents. This digestion has generally been cosidered to be mediated by a Ca++/Mg++ dependent endonuclease that is activated by increases in intracellular Ca2+. Morphologically apoptotic cells appear as small, condensed bodies. The chromatin is dense and fragmented, packed into compact membrane-bound bodies together with randomly distributed cell organelles. The plasma membrane shows extensive blebbing. It buds off projections so that the whole celi may split into several membranebound apoptotic bodies. Significant chemical changes take place in the plasma membrane. This helps in recognition of the apoptotic bodies by phagocytes. At this moment it is unclear if all cells can undergo apoptosis or it is a characteristic of only some tissues which are predisposed to apoptotic death being directly under the control of hormones or growth factors. This active form of cell death is controlled by a genetic program(s) that kills the targeted cell without causing subsequent inflammation. Tumor suppressor gene such as p 53 and oncogene such as bcl-2 are found to be closely related to apoptotic processes in a cell. Control of programmed cell death in normal and redundant cells could provide new implications for therapy in many conditions such as cancer, AIDS, leukemia, myocardial infarction and neurodegenerative diseases.