The spatial distribution of energy from ionizing radiations in cells is a strong determinant of radiobiological response. It is the objective of this research to derive an understanding of this dependence by the use of short-ranged radiation sources. In particular we intend to probe the mechanism(s) whereby chromosomal changes come about, on the understanding that chromosomal changes are intimately associated with cell death, mutation, anj cancer. We have successfully used Al soft X rays for radiobiological investigations and intend to construct a gas target (B,C,N,O,Ne,Ar) for incident protons as a source of a wide range of soft X rays with energy depositions down to about 200 eV with electron tracks of a few nanometers. We will also use soft neutrons which produce recoil Proton tracks of sub-micrometer ranges. This radiation source will provide information of direct relevance to radiation protection, where personnel exposure to soft neutrons carries an as yet undetermined risk. Thirdly, the localized energy depositions from I-125 disintegrations will be used to ask about the basis of aberration formation. Mammalian cells (human and hamster) will be irradiated at different stages of the cell cycle and the frequencies and types of chromosomal changes, cell survival and cytokinetic changes monitored. Low-dose studies emphasizing response and the basis thereof in the initial part of dose-response curves will be stressed. Analyses of responses will be oriented to distinction between models of biophysical action, e.g., """"""""critical lesion"""""""" versus """"""""dual lesion."""""""" The detailed track structures of the radiations will be calculated, and analyses of the biological responses will lead to predictions for other radiations. Stringent testing of models of biophysical action in this way will lead to model acceptance or rejection. In aiding understanding of mechanisms leading to the formation of chromosomal changes and to the biological effects of ionizing radiations, this proposal will impact significantly in areas concerned with optimization of radiation therapy and the determination of standards for human radiation protection.
