The objective of the research program is to understand cellular responses to radiation and chemical injury. Among these responses are processes of DNA repair and DNA rearrangement through homologous and non-homologous recombination pathways. It is likely that DNA repair and DNA recombination participate in cellular and genetic changes that occur in carcinogenesis. We intend to study the role of DNA damage, including UV, N-acetoxy-acetylaminofluorene, and 6-4 pyrimidine-pyrimidone adducts in homologous and non-homologous recombination processes in mammalian cells. We will study the basis for differences in response to UV damage in human and Chinese hamster ovary cell lines using DNA-mediated gene transfer methods. Somatic cell hybrids and UV-sensitive mammalian cell mutants will be used in these studies. Specially-constructed DNA sequences with fragments of mammalian genes will be introduced into mammalian cells by transfection and their recombination will be studied. The effects of damaging these gene fragments and pre-exposing cells to radiation will be investigated. The knowledge we will gain from these studies is directly relevant to the repair of DNA, cell recovery from DNA damaging treatments, mutagenesis, and carcinogenesis.
