Exposure to ionizing radiation is mutagenic as demonstrated in plants, microorganisms, and mammalian cells. Little is known, however, about the processes underlying radiation-induced mutations in mammalian cells, and how the mutagenic process is influenced by the mode of radiation delivery and/or repair processes. Using rodent and human cells, the main objectives of the proposed research are to determine, (1) the dose dependencies for mutation induction by fission-spectrum neutrons from the JANUS reactor, compared to X- or Gamma-rays, and to estimate the relative biological effectiveness (RBE) for this end point; (2) the effect on mutation induction of fractionation and protraction of the radiation dose, for high and low LET radiations (JANUS neutrons, and X or gamma rays, respectively), and whether the mode of delivery indicates a role of repair mechanisms; (3) the effects of different modes of delivery of fission neutrons on the incidence of neoplastic transformation, for comparison with mutation induction to see whether these two end points are mechnistically related; and (4) the interactions of high and low LET radiations in induction of mutation and neoplastic transformation, in order to obtain further insights about the possible mechanisms of their biological actions. The knowledge acquired through this project is also relevant to the understanding of hazards from high LET radiations and to the application of high LET radiations in tumor therapy.
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