Carbon ion radiation and clustered DNA double-strand breaks.

A carbon ion categorized as a heavy ion particle has been used for cancer radiotherapy. High linear energy transfer (LET) carbon ion irradiation deposits energy at a high density along a particle track, generating multiple types of DNA damage. Complex DNA lesions, comprising DNA double-strand breaks (DSBs), single-strand breaks, and base damage within 1-2 helical turns (<3-4nm), are thought to be difficult to repair and critically influence cell viability. In addition to the effect of lesion complexity, the most recent studies have demonstrated another characteristic of high LET particle radiation-induced DNA damage, clustered DSBs. Clustered DSBs are defined as the formation of multiple DSBs in close proximity where the scale of clustering is approximately 1-2μm³, i.e., the scale of the event is estimated to be > ∼1Mbp. This chapter reviews the hallmarks of clustered DSBs and how such DNA damage influences genome instability and cell viability in the context of high LET carbon ion radiotherapy.