Evidence of the involvement of p53 in γ-radiation-induced DNA repair in human lymphoblasts

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 p53(wt) and p53(mut) lymphoblasts. Mutation frequencies in the supF-tRNA target gene and survival of plasmids processed in p53(wt) and p53(mut) hosts were compared. Results: Mutation frequencies of oc-, uv- or linDNA were similar after processing in unirradiated p53(wt) and p53(mut) hosts. However, the mutation frequency of ocDNA and uvDNA decreased 50% when processed in irradiated p53(wt) hosts but was unaltered in irradiated p53(mut) hosts. In contrast, linDNA mutation frequencies varied similarly whether processed in irradiated p53(wt) or p53(mut) hosts: mutation frequency decreased twofold when linDNA was transfected immediately after host irradiation but increased twofold when transfection was delayed by 2 h. 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 p53(wt) and p53(mut) 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.