CELL-NUCLEUS AND DNA FRAGMENTATION ARE NOT REQUIRED FOR APOPTOSIS

Apoptosis is the predominant form of cell death and occurs under a var iety of physiological and pathological conditions. Cells undergoing ap optotic cell death reveal a characteristic sequence of cytological alt erations including membrane blebbing and nuclear and cytoplasmic conde nsation. Activation of an endonuclease which cleaves genomic DNA into internucleosomal DNA fragments is considered to be the hallmark of apo ptosis. However, no clear evidence exists that DNA degradation plays a primary and causative role in apoptotic cell death. Here we show that cells enucleated with cytochalasin B still undergo apoptosis induced either by treatment with menadione, an oxidant quinone compound, or by triggering APO-1/Fas, a cell surface molecule involved in physiologic al cell death. Incubation of enucleated cells with the agonistic monoc lonal anti-APO-1 antibody revealed the key morphological features of a poptosis. Moreover, in non-enucleated cells inhibitors of endonuclease blocked DNA fragmentation, but not cell death induced by anti-APO-1. These data suggest that DNA degradation and nuclear signaling are not required for induction of apoptotic cell death.