RADIATION-INDUCED SIGNAL-TRANSDUCTION AND STRESS-RESPONSE

Radiation-induced DNA damage can induce death by apoptosis by activati on of signal transduction pathways. One such pathway is the sphingomye lin/ceramide signal transduction pathway that is involved in initiatio n of stress-induced apoptosis in a variety of normal and neoplastic ce lls. This pathway is under regulation by the protein kinase C (PKC) pa thway that constitutes an anti-apoptosis mechanism. DNA damage can als o increase ceramide levels by activating the biosynthesis pathway, thr ough the activation of the ceramide synthase enzyme. Both pathways cou ld serve as potential targets for strategies that take advantage of si gnaling-based apoptosis to enhance cell killing in radiation therapy. (C) 1998 by Radiation Research Society.