In this study, we demonstrate for the first time that complement attack of
target cells, in the presence of suitably high levels of serum, can induce
the oligonucleosomal DNA fragmentation characteristic of apoptosis, This ph
enomenon requires membrane permeabilisation induced by formation of the com
plete membrane attack complex and relies on physiologically relevant levels
of serum. TUNEL analysis detected complement mediated DNA fragmentation as
early as 30 min after the addition of serum and electron microscopy confir
med that chromatin became condensed after complement attack. Various experi
ments implicate serum DNase I as the mediator of this DNA fragmentation. In
triguingly, membrane permeability induced by melittin gave rise to similar
serum dependent DNA fragmentation. The implications of these results for th
e study of apoptosis in vitro and in vivo are discussed.