Fritsche M, Haessler C, Brandner G
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene der Universität, Freiburg, Germany.
Oncogene. 1993 Feb;8(2):307-18.
Cancer therapy drugs, such as diamminedichloroplatinum (cisplatin), mitomycin C, etoposide and a number of other compounds, as well as energy-rich radiation, are known to act on cellular DNA. These agents are shown to induce nuclear accumulation of the so-called tumor-suppressor protein p53 in fibroblastoid cells, as well as in epithelioid normal and immortalized cells of murine, simian, and human origin. p53 accumulation starts a few hours after treatment and can remain detectable in surviving cells for at least 20 days. Accumulation occurs because of increased p53 protein stability and depends on ongoing translation. It is not the result of enhanced gene expression. A number of cell cycle inhibitors do not affect p53 protein accumulation, suggesting that the process may start from several points in the cell cycle. Since the increase in the nuclear p53 protein levels occurs within a few hours in most of the treated normal diploid cells, it is unlikely that the accumulated p53 protein is derived from a mutated p53 gene. The results obtained are in accordance with the view that the DNA damage-induced p53 accumulation may either inhibit cell growth, allowing DNA repair processes, or, in the case of severe damage, initiate apoptosis.
癌症治疗药物，如二氯二氨铂（顺铂）、丝裂霉素C、依托泊苷以及许多其他化合物，还有高能辐射，都已知会作用于细胞DNA。这些药物已被证明能在成纤维样细胞以及源自小鼠、猿猴和人类的上皮样正常细胞及永生化细胞中诱导所谓的肿瘤抑制蛋白p53在细胞核内积累。p53积累在治疗后数小时开始，并且在存活细胞中至少20天内都可检测到。积累的发生是由于p53蛋白稳定性增加，且依赖于正在进行的翻译过程，而非基因表达增强的结果。一些细胞周期抑制剂并不影响p53蛋白积累，这表明该过程可能从细胞周期的多个点开始。由于在大多数经处理的正常二倍体细胞中，细胞核内p53蛋白水平在数小时内就会升高，所以积累的p53蛋白不太可能源自突变的p53基因。所获得的结果与以下观点一致，即DNA损伤诱导的p53积累可能要么抑制细胞生长，使DNA修复过程得以进行，要么在严重损伤的情况下引发细胞凋亡。
