Induction of DNA Damage by Light Ions Relative to ⁶⁰Co γ-rays

The specific types and numbers of clusters of DNA lesions, including both DNA double-strand breaks (DSBs) and non-DSB clusters, are widely considered 1 of the most important initiating events underlying the relative biological effectiveness (RBE) of the light ions of interest in the treatment of cancer related to megavoltage x-rays and ⁶⁰Co γ-rays. This review summarizes the categorization of DNA damage, reviews the underlying mechanisms of action by ionizing radiation, and quantifies the general trends in DSB and non-DSB cluster formation by light ions under normoxic and anoxic conditions, as predicted by Monte Carlo simulations that reflect the accumulated evidence from decades of research on radiation damage to DNA. The significance of the absolute and relative numbers of clusters and the local complexity of DSB and non-DSB clusters are discussed in relation to the formation of chromosome aberrations and the loss of cell reproductive capacity. Clinical implications of the dependence of DSB induction on ionization density is reviewed with an eye towards increasing the therapeutic ratio of proton and carbon ion therapy through the explicit optimization of RBE-weighted dose.