The goal of these studies is to determine the molecular basis for the pronounced radioresistance of cultured TN-368 lepidopteran insect cells. The experimental approach is to examine several specific repair processes both on the molecular and cellular levels in the TN-368 cell line and, in addition, to determine the radiosensitivity of cell lines representing several other orders of insects for comparison with the TN-368 cells. Molecular repair studies to be performed include the comparative measurement of the size of the repaired region of DNA which has been damaged by both ultraviolet and gamma irradiations in TN-368 and IMR-90 cells, determination of the rate and extent of DNA double strand break rejoining, and the measurement of the removal of endonuclease sensitive sites from the DNA. These molecular investigations will be correlated with cellular examinations of sublethal, potentially lethal, and inducible repair processes as assayed by cell survival (colony formation). TN-368 cell mutants sensitive to ultraviolet light and gamma radiation will be isolated for the purpose of determining differences in the repair processes between wildtype and mutant cells. A major project involved in the characterization of sensitive mutants will be the determination of mutation frequencies in the TN-368 cells. The results of these experiments are expected to produce important information on molecular and cellular mechanisms for dealing with radiation damage which may be applied to mammalian cells. As repair mechanisms appear to play a significant role in radioresistance, these studies should be of value in better understanding mechanisms of mutagenesis and carcinogenesis.
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