Apoptosis: an indicator of radiosensitivity in vitro?
The mechanisms by which ionizing radiation kills cells was a topic of great interest to Dr Alper, and one suspects that she would have delighted in 'clarifying' the role of apoptosis. Indeed, clarification seems necessary in view of the abundance of often conflicting data currently emerging. However, given some simplifying assumptions, important patterns can be discerned. The following comments are thus framed in the context of haematopoietic cell lines, which generally undergo rapid apoptosis (within hours) following irradiation, in contrast to cells of non-haematopoietic origin, which are more likely to be characterized by delayed apoptosis (within days). Tolerance for DNA damage appears to be reduced in cells capable of rapid apoptosis, and those cells are sensitized to ionizing radiation when the apoptotic response mechanisms are fully functional. This rapid apoptotic response shows minor sensitivity to cell cycle position or radiation dose rate. Different considerations apply, however, for the delayed response. Delayed apoptosis appears to be triggered by chromosome damage, and evidence implicating delayed apoptosis as a modifier of cellular radiosensitivity is much less convincing at present.
Olive
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PL
Medical Biophysics Department, British Columbia Cancer Research Centre, Vancouver, Canada.
Durand
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RE
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002453:Cell Cycle / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects*; D002478:Cells, Cultured / Q000528:radiation effects; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D015398:Signal Transduction