Li G, Ho V C
Department of Medicine, Vancouver Hospital and Health Sciences Centre, University of British Columbia, Canada.
Br J Dermatol. 1998 Jul;139(1):3-10.
p53 plays an essential part in the maintenance of the cellular genetic stability after a DNA-damaging event such as ultraviolet (UV) radiation. Following UV radiation, the amount of p53 protein is elevated. The increased p53 is believed to induce cell cycle arrest, promote nucleotide excision repair (NER) and apoptosis. To study if cells respond differently to high- and low-dose UV radiation, we examined the DNA repair efficiency and apoptosis rate of human and murine fibroblasts after UV radiation. Using a host cell reactivation assay, we found that NER was increased after low doses but not after high doses of UV radiation. In contrast, apoptosis occurred only after the cells received high doses (over 200 J/m2), but not low doses of UVB. The induction of both NER and apoptosis was observed only in p53+/+ murine fibroblasts, not in p53-/- cells, indicating that both stress response mechanisms are dependent on wild-type p53 function. UV radiation induced the expression of p53 protein in a dose-dependent manner up to 400 J/m2. In contrast, p21waf1/cip1 was induced only after low doses and bax only after high doses of UV radiation, supporting the roles of p21waf1/cip1 and bax in NER and apoptosis, respectively. Taken together, these results indicate that cellular stress response to UV radiation depends on UV dose, DNA repair after low doses and apoptosis after high doses, and that both mechanisms are dependent on wild-type p53 function.
在诸如紫外线（UV）辐射等DNA损伤事件后，p53在维持细胞遗传稳定性方面起着至关重要的作用。紫外线辐射后，p53蛋白的量会升高。增加的p53被认为可诱导细胞周期停滞、促进核苷酸切除修复（NER）和细胞凋亡。为了研究细胞对高剂量和低剂量紫外线辐射的反应是否不同，我们检测了紫外线辐射后人源和鼠源成纤维细胞的DNA修复效率和凋亡率。使用宿主细胞再激活试验，我们发现低剂量紫外线辐射后NER增加，而高剂量后则没有增加。相反，细胞凋亡仅在接受高剂量（超过200 J/m2）紫外线B辐射后发生，低剂量时未发生。仅在p53+/+鼠源成纤维细胞中观察到NER和细胞凋亡的诱导，而在p53-/-细胞中未观察到，这表明两种应激反应机制均依赖于野生型p53功能。紫外线辐射以剂量依赖的方式诱导p53蛋白表达，直至400 J/m2。相比之下，p21waf1/cip1仅在低剂量后被诱导，而bax仅在高剂量紫外线辐射后被诱导，分别支持了p21waf1/cip1和bax在NER和细胞凋亡中的作用。综上所述，这些结果表明细胞对紫外线辐射的应激反应取决于紫外线剂量，低剂量后进行DNA修复，高剂量后发生细胞凋亡，并且这两种机制均依赖于野生型p53功能。
