Radiation-induced signal transduction and stress response

Radiation-induced DNA damage can induce death by apoptosis by activation of signal transduction pathways. One such pathway is the sphingomyelin/ceramide signal transduction pathway that is involved in initiation of stress-induced apoptosis in a variety of normal and neoplastic cells. This pathway is under regulation by the protein kinase C (PKC) pathway that constitutes an anti-apoptosis mechanism. DNA damage can also increase ceramide levels by activating the biosynthesis pathway, through the activation of the ceramide synthase enzyme. Both pathways could serve as potential targets for strategies that take advantage of signaling-based apoptosis to enhance cell killing in radiation therapy. (C) 1998 by Radiation Research Society.