Apoptotic Morphology Reflects Mitotic-like Aspects of Physiological Cell Death and is Independent of Genome Digestion

Several hallmarks characterize what has come to be recognized as a common physiological process of cell death. In particular, the two defining characteristics are the apoptotic morphology of cell shrinkage and chromatin condensation originally described by Kerr et al. [(1972) Br. J. Cancer, 26:239-256] and the prelytic digestion of genomic DNA of the dying cell, as noted first by Wyllie [(1980) Nature, 284:555-556] and Russell et al. [(1982) J. Immunol., 128:2087-2094]. Many suicidal stimuli are able to modulate this process; each of these suicidal inducers activates cell death via a specific pathway. While it remains to be established, we hypothesize that a single mechanism of physiological cell death pertains in all cases [Ucker (1991) New Biol., 3:103-109; Ucker et al. (1994) Immunol. Rev., 142:273-299]. The various modulatory processes act afferently on this single effector pathway. We have examined the significance of the hallmarks of physiological cell death in an effort to elucidate critical mechanistic elements of the cell death process. Here we describe our recent studies of genome digestion. Our work has centered on the characterization of a set of fibroblastic cell clones that vary in their ability to undergo genome digestion associated with physiological cell death induced by cytotoxic T lymphocytes (CTL) and other stimuli. Our results demonstrate that genome digestion is dispensable for physiological cell death and that apoptotic morphology is independent of genome digestion. Our data suggest further that apoptotic morphology is reflective of mitotic-like aspects of the cell death process.