The use of DNA double-strand break quantification in radiotherapy

DNA double-strand breaks (DSB) are an important direct consequence of treat ing cells with ionizing radiation. A variety of evidence points toward DSBs being the key damage type linked to radiation-induced lethality. In partic ular, the link between DSB and chromosome breakage, which in turn closely c orrelates with cell death in some cell types, is strongly supportive of thi s concept. There has been much interest in the possibility of using measure s of strand breaks as a pretreatment test of radiation response. This has l argely been in the contest of assessing inherent cellular sensitivity throu gh 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 assay s, but it is more likely to reflect the fact that the radiosensitivity of c ells 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 dam age, and these can be triggered by damage other than DSB, It is therefore p ossible that while DSBs are clearly important-and they may be the single mo st important lesion in some types-other damage types may be significant tri ggers of cell death pathways after ionizing radiation treatment. (C) 2001 E lsevier Science Inc.