This application proposes a study of mutation and/or transformation damage and repair caused by fission spectrum neutrons in rodent and human cells lines. We plan to investigate the large enhancement of transformation frequency observed when cells from the C3H 10T1/2 mouse cell line are exposed to protracted doses of neutrons. In contrast, cell killing and mutation in these cells do not appear to be influenced to any large degree by protracted exposures to neutrons when compared to exposures delivered at high dose rates. Three specific areas will be addressed: 1. Mode of radiation-delivery: Particular importance will be placed on very low dose rate and dose fractionation studies to further delineate the extent of the enhanced transformation frequency and nature of the small effects on mutation frequency. 2. Neutron action at cellular level: In earlier studies, at least for transformation, we have postulated that the repair processes following neutron irradiation may be prone to mistakes. We plan to examine the possibility that this misrepair would lead to heritable permanent changes in cells by looking at the sensitivity to cell killing, mutation, and transformation in the progeny of cells from neutron-irradiated populations. We also plan to examine concurrently the karyotypes of treated cells to determine if there are any systematic changes at the chromosome level that could be correlated to changes in sensitivity or mutability. 3. Neutron action at molecular level: There is little information about the effects of neutrons on DNA. We plan to use alkaline and neutral elution techniques to determine the number of single- and double-strand breaks and the quantity of protein-to-DNA crosslinking occurring under various treatment regimens. These examinations may enable us to correlate the type of damage and repair of damage at the DNA level with the quantity of transformation or mutations seen.
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