This "core" scientific component is designed to address one of the central questions in radiation biology, namely the hierarchical progression of radiation damage from energy deposition, through DNA strand-break induction and repair, through mutational/chromosomal damage, and finally to survival or oncogenesis. The experiments will be carried out within the other projects of this proposal, which is the rationale for designating this as a "core". We shall coordinate and carry out experimental design for two sets of experiments on dose/LET response relations in human epithelial cells and in Syrian hamster embryo cells. The endpoints chosen reflect increasing "complexity" of damage, ranging from DNA strand breaks, to PCC, to mutation, to chromosomal aberration, and to oncogenic transformation. The resulting data will be the first in which the same cell lines are assayed for a hierarchical series of endpoints, from the simple to the complex. Experimental results will be analyzed statistically using consistent, state-of-the-art techniques. Using these data, development will continue of consistent mechanistic models to simulate the various steps in the hierarchical development of radiation damage. These start with calculation of track structure at the nanometer level, followed by calculation of DSB yields, based on yields of local multiply-damaged sites. The approach will be extended so that individual chromosomes are confined, at irradiation, to separate regions. Mutant deletion sizes will be investigated using a stimulation of the loop domain of interphase chromatin. Calculations of the time- and distance-dependent history of DSB, in terms of competition between restitution and exchange interaction, will be made, yielding exchange- type aberration yields. Consideration will be given to a possible subset of severely-damaged slowly repairing DSB. Links between aberration/mutation formation and oncogenesis will be investigated, specifically for breast cancers.