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MS Cragg1, WJ Howatt2, L Bloodworth1, VA Anderson1, BP Morgan3 & MJ Glennie1
1Cancer Sciences Division, Tenovus Laboratory, Southampton University Hospital, Southampton SO16 6YD
2University Medicine, Southampton University Hospital, Southampton SO16 6YD
3Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff, CF4 4XN
Correspondence to: MS Cragg, Cancer Sciences Division, Tenovus Laboratory, Southampton University Hospital, Southampton SO16 6YD, Tel: 01703 798566; Fax: 01703 704061; E-mail: msc@soton.ac.uk.
Edited by D Green
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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 phenomenon requires membrane permeabilisation induced by formation of the complete 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 confirmed that chromatin became condensed after complement attack. Various experiments implicate serum DNase I as the mediator of this DNA fragmentation. Intriguingly, membrane permeability induced by melittin gave rise to similar serum dependent DNA fragmentation. The implications of these results for the study of apoptosis in vitro and in vivo are discussed. Cell Death and Differentiation (2000) 7, 48 – 58.
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