Differential inhibition of radiation-induced apoptosis.
The most common mechanism by which radiation kills cells is the induction of DNA double-strand breaks that results in the loss of cell proliferation. Even though apoptosis is increasingly identified in experimental 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 antiapoptotic signaling that affects the apoptotic outcome in irradiated mammalian cells. In particular, we will concentrate on the sphingomyelin/ceramide signal transduction pathway which is involved in initiation of stress-induced apoptosis in a variety of normal and neoplastic cells. We will also discuss the crosstalk between the sphingomyelin/ceramide pathway and the protein kinase C pathway which constitutes an antiapoptotic pathway, and the potential for pharmacological modulation to increase the fraction of apoptotic cells undergoing apoptosis after radiation exposure.
Haimovitz-Friedman
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Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Kolesnick
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RN
Fuks
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage; D004789:Enzyme Activation; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism*
D016222:Fibroblast Growth Factor 2; D011493:Protein Kinase C