Initiation of ionizing radiation-induced apoptosis: DNA damage-mediated or does ceramide have a role?
OBJECTIVE
To critically review the data supporting membrane damage-induced increases in ceramide levels as the primary initiator of ionizing radiation-induced apoptosis and to point out that there is compelling evidence supporting the involvement of DNA damage in this process.


CONCLUSIONS
There is now a significant literature suggesting that irradiation of cells can quickly lead to a modest, transitory increase in the level of the putative second messenger ceramide. These results have been used to support the views that membrane damage is the primary trigger for radiation-induced apoptosis and that DNA damage is irrelevant to this process. It is argued, however, that the data are inadequate to support such conclusions because it is questionable whether the induced levels of ceramide are toxic and because the ceramide hypothesis cannot convincingly explain the delayed apoptosis, dependent on events such as mitosis, that is shown by many cell lines. In contrast, it is suggested that the sensitivity of some cell types to the induction of apoptosis by DNA-targeted radiation damage, the relationship between p53 status and radiation response, and the influence of enzymatic DNA repair capability on susceptibility to apoptosis, argue strongly that DNA damage is relevant to the triggering of apoptosis.
Radford
I R
IR
Sir Donald and Lady Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia. i.radford@pmci.unimelb.edu.au
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002462:Cell Membrane / Q000528:radiation effects; D002518:Ceramides / Q000032:analysis / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D013108:Sphingomyelin Phosphodiesterase / Q000502:physiology
D002518:Ceramides; D013108:Sphingomyelin Phosphodiesterase