Different modes of cell death and related phenomena: a proposal for a meaningful terminology in relation to tests of...

The terms death (as an irreversible occurrence), necrosis and apoptosis are well defined and generally accepted in cell biology. Procedures and terminology related to estimation of different forms of cell mortality are, however, less clear and exact. Evaluation of the rate of mortality is important for numerous biological processes such as growth, atrophy, regeneration and neoplasia. Procedures used for assessing cell mortality include: 1. dye exclusion tests which were shown to be inadequate in apoptosis; 2. release of radioactive markers, also inadequate, as they occur also in life during shedding of membranes and cleavage of cell parts; 3. morphological and histochemical procedures which show only relatively late changes (autolysis) in cells which have not yet been completely obliterated; 4. absence of synthetic activities, which do not necessarily indicate death (e.g. mature erythrocytes); 5. colony forming capacity in cultures, which are considered by most authors as the most useful tests for assessing the effects of cytotoxic treatments. These tests do not, however, assess viability, but rather reproductive capacity. In all these tests, delayed changes in vitality can be determined by repeated or continuous testing. The following new terms are proposed and related to presently available tests. Aposchisis--for cleavage of cell parts not necessarily associated with cell death. N-mortality--for necrosis type of mortality estimated by the dye exclusion tests. A-mortality--for apoptosis type of mortality, which cannot be directly estimated at present. Acarpy--for loss of reproductive capacity of cells which is assessed by the colony forming tests.