LET Dependence of Linear and Quadratic Terms in Dose-Response Relationships for Cellular Damage: Correlations with the Dimensions and Structures of Biological Targets

Abstract

Abstract Dose-effect relationships and the dependence of RBE on LET can be analysed to derive insights about the amounts of deposited radiation energy required in critical structures and about the dimensions of targets involved in the induction of various cellular responses. Amounts of energy of several hundreds of eV and dimensions of the order of 10 nm have been derived as critical values associated with the induction of cell reproductive death and chromosome aberrations, while effective cross sections are of the order of tens of square micrometres. To apply information from microdosimetric studies and from cellular responses to the development and testing of hypotheses about mechanisms of radiation action, it is necessary to correlate these data with insights concerning dimensions and structures of cellular constituents and macromolecules. This approach is illustrated by the correlation of cross sections for inactivation with dimensions of the cell nucleus in dependence on the culture conditions and by the comparison of the derived dimensions of critical targets with DNA packing and chromatin structure in cells. A model is suggested in which lethal and potentially lethal damage induced in mammalian cells by single ionising particles involves the induction of two DNA double strand breaks in close proximity in a chromatin fibre, while accumulation of damage causing the contribution, which increases with the square of the dose, might be associated with interaction of single DSBs produced at larger distances.