Our long-term goal is to provide a comprehensive picture of the spectrum of genetic damages produced in mammalian cells by ionizing radiation (as a model) at the low doses (<10 R) and dose rates relevant to most human exposures, and to develop quantitative methodologies to assess the impact of genetic damage on cancer and other human disease. The collaboration between the Eleanor Roosevelt Institute for Cancer Research (ERICR), Denver, and the Department of Radiology and Radiation Biology, Colo. State Univ. (CSU), Ft. Collins, has greatly facilitated our interrelated studies of the overall genetic effects of low-level exposure. The groups at ERICR and CSU have experience in analysis of mutation, and chromosome aberrations, respectively. The goal of this proposal is to measure gene and chromosome mutations, on the one hand, and chromosome aberrations, on the other, so as to illuminate relationships between them; to begin to define the role of DNA repair; to analyze mutation at the DNA level, and to develop theoretical models to relate them. Specifically we will: (1) employ the AL hamster hybrid cell method to quantify gene and chromosome mutation and cytogenetically examine AL mutants to correlate chromosome aberrations with mutation; (2) establish how varying the dose rate alters the frequency and kinds of mutants and aberrations produced; (3) Begin, by DNA restriction analysis, to investigate mechanisms of mutagenesis; (4) extend all these studies to new human-hamster hybrids that contain additional human chromosomes which will increase target size and permit assessment of translocation and nondisjunction using genetic and in situ fluorescence cytogenetics techniques; (5) carry out these studies on other hybrids defective in particular aspects of repair; and (6) continue to develop and experimentally test mathematical models relating dose response relationships of cell-killing, and mutation and especially translocations.
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