Mallya S M, Sikpi M O
Department of Oral Diagnosis, School of Dental Medicine, University of Connecticut Health Center, Farmington 06030, USA.
Int J Radiat Biol. 1998 Aug;74(2):231-8. doi: 10.1080/095530098141618.
To determine the involvement of p53 in ionizing radiation-induced excision and recombination repair.
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.
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.
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.
确定p53在电离辐射诱导的切除和重组修复中的作用。
含有辐射诱导的单链断裂加碱基损伤（ocDNA）、紫外线辐射损伤（uvDNA）或限制性内切酶产生的双链断裂（linDNA）的穿梭载体pZ189在未照射或照射过的p53野生型和p53突变型淋巴母细胞中进行处理。比较了在p53野生型和p53突变型宿主中处理的supF-tRNA靶基因的突变频率和质粒的存活率。
在未照射的p53野生型和p53突变型宿主中处理后，ocDNA、uvDNA或linDNA的突变频率相似。然而，在照射过的p53野生型宿主中处理时，ocDNA和uvDNA的突变频率降低了50%，但在照射过的p53突变型宿主中未发生改变。相比之下，无论在照射过的p53野生型还是p53突变型宿主中处理，linDNA的突变频率变化相似：宿主照射后立即转染linDNA时，突变频率降低两倍，而转染延迟2小时时，突变频率增加两倍。通过linDNA产生的子代数量与未受损pZ189产生的子代数量之比确定的双链断裂重新连接能力，在照射过的p53野生型和p53突变型宿主中在定性和定量上均有所不同。
这些研究表明电离辐射可诱导哺乳动物细胞中的DNA修复，并表明p53参与调节切除修复保真度和双链断裂重新连接能力。
