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 level of the plasma membrane. Proteins involved in DNA damage recognition include poly(ADP ribose) polymerase (PARP), DNA‐dependent protein kinase, p53 and ataxia‐ telangiectasia mutated (ATM). Many of these proteins are inactivated by caspases during the execution phase of apoptosis. Signalling pathways outside the nucleus involve tyrosine kinases such as stress‐activated protein kinase (SAPK)/c‐Jun N‐terminal kinase (JNK), protein kinase C, ceramide and reactive oxygen species. Recent evidence shows that tumour cells resistant to ionizing radiation‐induced apoptosis have defective ceramide signalling. How these signalling pathways converge to activate the caspases is presently unknown, although in some cell types a role for calpain has been suggested.