The use of DNA double-strand break quantification in radiotherapy

DNA double-strand breaks (DSB) are an important direct consequence of treating cells with ionizing radiation. A variety of evidence points toward DSBs being the key damage type linked to radiation-induced lethality. In particular, the link between DSB and chromosome breakage, which in turn closely correlates with cell death in some cell types, is strongly supportive of this concept. There has been much interest in the possibility of using measures of strand breaks as a pretreatment test of radiation response. This has largely been in the contest of assessing inherent cellular sensitivity through damage induction or repair parameters. A number of studies have produced hopeful results, but overall there has been no parameter that can reliably predict radiosensitivity, This may be due to the inadequacies of the assays, but it is more likely to reflect the fact that the radiosensitivity of cells is dictated hy a whole series of events; alterations in many of these can alter the overall response. In addition, it is now recognized that cell-signalling pathways form an essential part of the cellular response to damage, and these can be triggered by damage other than DSB, It is therefore possible that while DSBs are clearly important-and they may be the single most important lesion in some types-other damage types may be significant triggers of cell death pathways after ionizing radiation treatment. (C) 2001 Elsevier Science Inc.