DNA double-strand breaks (DSBs) are induced by ionizing radiation (IR) and 
various radiomimetic agents directly, or indirectly as a consequence of DNA 
repair, recombination and replication of damaged DNA. They are ultimately 
involved in the generation of chromosomal aberrations and were reported to cause 
genomic instability, gene amplification and reproductive cell death. To address 
the question of whether DSBs act as a trigger of apoptosis, we induced DSBs by 
means of restriction enzyme electroporation and compared the effect with IR in 
mouse fibroblasts that differ in p53 status [wild-type (+/+) versus 
p53-deficient (-/-) cells]. We show that (i) electroporation of PVU:II is highly 
efficient in the induction of DSBs, (ii) electroporation of PVU:II increases the 
rate of apoptosis, but not of necrosis in p53-/- cells, (iii) treatment with 
gamma-rays induces both apoptosis and necrosis in p53-/- cells, (iv) the 
frequency of DSBs correlates with the yield of apoptosis and (v) both PVU:II and 
gamma-ray treatment reduce the level of anti-apoptotic Bcl-2 protein in p53-/- 
cells whereas the level of Bax remains unaltered. Cells expressing wild-type p53 
were more resistant than p53-deficient cells as to the induction of apoptosis 
and did not show Bcl-2 decline upon treatment with PVU:II and gamma-rays. The 
data provide evidence that blunt-ended DSBs induced by restriction enzyme PVU:II 
act as a highly efficient trigger of apoptosis, but not of necrosis. This 
process is related to Bcl-2 decline and does not require p53.