Stochastic modeling of p53-regulated apoptosis upon radiation damage

Studying cellular response to radiation damage is important from the perspectives of both radiotherapy and the mitigation of radiation damage. In the case of the former, the goal is the induction of cell death, whereas in the latter case a cellular response leading to organismal survival is required. The fate of the organism after radiation damage is linked in a complex manner to cellular fate. In the short term, an extensive cell death due to radiation damage will lead to the death of the organism. In the long term (relevant only if the organism survives the short term effects), it the survival of healthy and robust cells that dictate the organism’s survival (for example, absence of long term cancerous cells). In this manuscript, we focus on the immediate survival of the organism after radiation damage. The mechanism of cell death after radiation damage is purported to be apoptosis via caspase activation that occurs several hours after radiation injury. Thus, it is natural to investigate cellular apoptotic machinery. Cellular response to radiation is very complex and involves, possibly, proteins that respond to DNA damage and the formation of free radicals that modify cellular biochemistry. Although the exposure to radiation may be momentary, the effect of the exposure on cellular biochemistry may be long lived. Further, several proteins that are expressed transiently after radiation damage, may trigger downstream response such as caspase activity that occurs long after their expression. In view of the complex cellular response, protein–protein interactions that lead to that response, and possible importance of temporal evolution of the system, it is important to study systemically the time-dependent cellular response to stress.