The relationships between RBE and LET for different types of lethal damage in mammalian cells: biophysical and molecular mechanisms.

The relative biological effectiveness (RBE) of radiations as a function of linear energy transfer (LET) is analyzed for different types of damage causing reproductive death of mammalian cells. Survival curves are evaluated assuming a linear-quadratic dose dependence of the induction of reproductive death of cells. The linear term represents damage from single particle tracks and the quadratic term represents damage due to interaction of lesions from independent tracks. Differences and similarities are discussed of the LET dependence of single-track lethal damage, sublethal damage, potentially lethal damage and DNA double-strand breaks. The RBE-LET relationships are correlated with local energy deposition in small regions of the cells. The analysis shows that single-track lethal damage is composed in part of a type of damage that is not repaired by delayed plating and is very strongly dependent on LET with maximum RBE values up to 20, while another component consists of potentially lethal damage that is weakly dependent on LET with maximum RBE values less than 3. Potentially lethal damage and sublethal damage depend similarly on LET as DNA double-strand breaks. The sector of single-track damage which is not repaired by delayed plating is hypothesized to be caused through a repair-exchange mechanism involving two double-strand breaks induced close together. The identification of these different components of damage leads to an interpretation of differences in radiosensitivity and in RBE-LET relationships among various types of cells.