Molecular mechanisms of ionizing radiation-induced apoptosis

Ionizing radiation activates not only signalling pathways in the nucleus as a result of DNA damage, but also signalling pathways initiated at the leve l of the plasma membrane. Proteins involved in DNA damage recognition inclu de poly(ADP ribose) polymerase (PARP), DNA-dependent protein kinase, p53 an d ataxia-telangiectasia mutated (ATM). Many of these proteins are inactivat ed by caspases during the execution phase of apoptosis. Signalling pathways outside the nucleus involve tyrosine kinases such as stress-activated prot ein kinase (SAPK)/c-Jun N-terminal kinase (JNK), protein kinase C, ceramide and reactive oxygen species. Recent evidence shows that tumour cells resis tant to ionizing radiation-induced apoptosis have defective ceramide signal ling. How these signalling pathways converge to activate the caspases is pr esently unknown, although in some cell types a role for calpain has been su ggested.