Enhanced expressions of glucose-6-phosphate dehydrogenase and cytosolic aldehyde dehydrogenase and elevation of reduced glutathione level in cyclophosphamide-resistant human leukemia cells

PURPOSE: To determine the involvement of p53 in ionizing radiation-induced excision and recombination repair. MATERIALS AND METHODS: Shuttle vector pZ189 containing radiation-induced single strand breaks plus base damage (ocDNA), ultraviolet-radiation damage (uvDNA), or a restriction enzyme-produced double strand break (linDNA) were processed in unirradiated or irradiated p53wt and p53mut lymphoblasts. Mutation frequencies in the supF-tRNA target gene and survival of plasmids processed in p53wt and p53mut hosts were compared. RESULTS: Mutation frequencies of oc-, uv- or linDNA were similar after processing in unirradiated p53wt and p53mut hosts. However, the mutation frequency of ocDNA and uvDNA decreased 50% when processed in irradiated p53wt hosts but was unaltered in irradiated p53mut hosts. In contrast, linDNA mutation frequencies varied similarly whether processed in irradiated p53wt or p53mut hosts: mutation frequency decreased twofold when linDNA was transfected immediately after host irradiation but increased twofold when transfection was delayed by 2h. Double strand break rejoining capacity, determined by the ratio of the number of progenies from linDNA to that from undamaged pZ189, differed both qualitatively and quantitatively in irradiated p53wt and p53mut hosts. CONCLUSIONS: These studies show induction of DNA repair in mammalian cells by ionizing radiation and indicate the involvement of p53 in the modulation of excision repair fidelity and double strand break rejoining capacity.