Chemical aspects of clustered DNA damage induction by ionising radiation.

Ionising radiation induces a variety of chemical modifications to DNA, ranging from simple, isolated lesions to clustered DNA damage, in which two or more lesions are formed within a few tens of base pairs by a single radiation track. Multiple lesions, e.g. tandem lesions and amplification of damage, may also be induced in DNA by reaction with a single hydroxyl radical. It has been proposed from biophysical modelling that clustered DNA damage is less repairable and therefore contributes to the biological severity of ionising radiation. In this review, some evidence is presented which indicates that non-double strand break (non-DSB) clustered DNA damage is induced in significant yield, relative to that of DSBs, in mammalian cells. Enzymatic processing of clustered DNA damage in synthetic oligonucleotides has been shown to be compromised, depending on the nature of the lesions present. The role of clustered DNA damage in the early stages of the development of radiation-induced carcinogenesis remains to be addressed.