The overall objective of this project is to obtain information on specific types of radiation-induced DNA base lesions and their biological consequences in vivo and in vitro. The quantities and types of base lesions will be determined in the DNA of bacterial strains selected for their known sensitivities to ionizing radiation and for their genetically characterized ability to repair radiation damage. Specific base lesions will be identified and quantitated by various kinds of chromatography including HPLC, and 13C-NMR as a function of radiation dose, level of survival, and time after irradiation during the period in which radiation damage to DNA is though to be repaired. Monoclonal antibody assays will be developed for specific base lesions to enable their detection at low, biologically relevant doses. The effects of the hydroxyl radical, oxygen, radioprotective and radiosensitizer compounds on the types and quantities of base damage will be determined. From studies involving model systems in vitro, the relationships between damage to DNA bases and mutagenesis will be delineated. Certain in vitro studies on the effects of radiation on DNA base and sugar constituents will be carried out when the data from such studies are needed to interpret in vivo results and cannot be found in available literature. The information obtained from this project will make available more substantive data on the destruction of DNA bases as it occurs in vivo by ionizing radiation. These data also will allow, for the first time, a direct assessment of the applicability of much of the previous research on the radiation chemistry of DNA and its constituents in vitro to actual in vivo damage. New insights may be provided into the chemical basis for the oxygen effect and for the modification of radiation response by various compounds with potential application in cancer radiotherapy.
Showing the most recent 10 out of 15 publications
