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 functio n of linear energy transfer (LET) is analyzed for different types of d amage causing reproductive death of mammalian cells. Survival curves a re evaluated assuming a linear-quadratic dose dependence of the induct ion of reproductive death of cells. The linear term represents damage from single particle tracks and the quadratic term represents damage d ue to interaction of lesions from independent tracks. Differences and similarities are discussed of the LET dependence of single-track letha l damage, sublethal damage, potentially lethal damage and DNA double-s trand breaks. The RBE-LET relationships are correlated with local ener gy deposition in small regions of the cells. The analysis shows that s ingle-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 max imum RBE values less than 3. Potentially lethal damage and sublethal d amage depend similarly on LET as DNA double-strand breaks. The sector of single-track damage which is not repaired by delayed plating is hyp othesized to be caused through a repair-exchange mechanism involving t wo double-strand breaks induced close together. The identification of these different components of damage leads to an interpretation of dif ferences in radiosensitivity and in RBE-LET relationships among variou s types of cells.