DIFFERENTIAL INHIBITION OF RADIATION-INDUCED APOPTOSIS

The most common mechanism by which radiation kills cells is the induct ion of DNA double-strand breaks that results in the loss of cell proli feration. Even though apoptosis is increasingly identified in experime ntal systems in vitro and in vivo, it is still generally regarded as a rare mode of radiation-induced cell kill with minor relevance for the clinical effects of radiation. This review will focus on pro-and anti apoptotic signaling that affects the apoptotic outcome in irradiated m ammalian cells. In particular, we will concentrate on the sphingomyeli n/ceramide signal transduction pathway which is involved in initiation of stress-induced apoptosis in a variety of normal and neoplastic cel ls. We will also discuss the crosstalk between the sphingomyelin/ceram ide pathway and the protein kinase C pathway which constitutes an anti apoptotic pathway, and the potential for pharmacological modulation to increase the fraction of apoptotic cells undergoing apoptosis after r adiation exposure.