Donner E M, Preston R J
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.
Carcinogenesis. 1996 May;17(5):1161-5. doi: 10.1093/carcin/17.5.1161.
The involvement of p53 in the formation of chromosome aberrations was assessed by analyzing bleomycin-induced, chromatid-type aberrations in G2 phase fibroblasts derived from embryos from wild-type and p53 knock-out mice. Cells that were p53+/- or p53-/- were more sensitive to the induction of aberrations than the p53+/+ cells, particularly at concentrations of 7.5 and 10.0 microg/ml. The p53-deficient cells also showed an overdispersed distribution of bleomycin-induced chromatid aberrations, a greater amount of overall genomic instability and a possible loss of a cell death pathway. These data are interpreted as indicating a role for p53 in DNA repair in the G2 phase, with a loss of p53 leading to an increased frequency of deletions (incomplete repair) and interchanges (misrepair). The specific role remains to be elucidated. The mitotic index decreased with increasing bleomycin concentration to a similar extent in all three cell lines, indicating that the loss of a G2 checkpoint in p53-/- and p53+/- cells was not an explanation for the increased sensitivities in these cells compared with the p53+/+.
通过分析来自野生型和p53基因敲除小鼠胚胎的G2期成纤维细胞中博来霉素诱导的染色单体型畸变，评估p53在染色体畸变形成中的作用。与p53+/+细胞相比，p53+/-或p53-/-细胞对畸变的诱导更敏感，尤其是在7.5和10.0微克/毫升的浓度下。p53缺陷细胞还表现出博来霉素诱导的染色单体畸变的过度分散分布、更大程度的整体基因组不稳定性以及细胞死亡途径的可能丧失。这些数据被解释为表明p53在G2期DNA修复中起作用，p53的缺失导致缺失（不完全修复）和互换（错误修复）频率增加。具体作用仍有待阐明。在所有三种细胞系中，有丝分裂指数随着博来霉素浓度的增加而下降到相似程度，这表明与p53+/+细胞相比，p53-/-和p53+/-细胞中G2检查点的丧失并不能解释这些细胞敏感性增加的原因。
