The case against apoptosis

Apoptosis is not as dominant a process in cell loss from normal tissues and tumours as has sometimes been claimed. The term 'programmed cell death', which many authors regard as synonymous with apoptosis, is an unsatisfactory term that is best avoided. In studies on the response of tumours to drug and radiation treatment, the use of apoptosis assays concentrates attention on the first decade of cell killing (0-90%), whereas the outcome of treatment depends on multi-log cell kill; an assay of clonogenic cell survival is the appropriate method for this purpose. Loss of colony-forming ability is the key event in treated tumour cells, and the appearance of morphological and molecular evidence of apoptosis is probably downstream from this event. Published studies that have compared apoptosis and cell survival responses in tumour cells have generally failed to find a causal relationship.