Use of radiation quality as a probe for DNA lesion complexity

Abstract

A number of studies have examined the possible relationships between either initial levels of DNA double-strand break (dsb) induction, their rejoining kinetics, or residual dsb and lethality in mammalian cells. With radiations of differing linear energy transfer (LET), the relative biological effectiveness (RBE) for dsb induction (20-100 keV/microns) has been lower than the RBEs measured for cell survival, and in many cases are around unity. Several studies have shown differences in the rejoining of dsb with less dsb rejoined after high than after low LET irradiation. These results suggest that there may be differences in the types of lesions being induced by different radiations and scored as DNA dsbs using current techniques. From modelling studies it is known that there is a range of energy deposition event sizes likely to occur in DNA, and there may also be uniquely large energy depositions associated with high LET radiations, particularly for large target sizes associated with the higher levels of chromatin structure. Many lesions induced will be clustered at the sites of these energy depositions. Assays need to be developed to measure complex lesions in both model DNA and cellular systems. Different levels of complexity need to be considered such as clustering of radicals close to DNA, localized areas of DNA damage (1-15 bp) and lesions which may be induced over larger distances related to higher-order structure. The use of radiations of differing LET will be an important probe in understanding DNA lesion complexity.