Cui Y F, Zhou P K, Woolford L B, Lord B I, Hendry J H, Wang D W
Institute of Radiation Medicine, Beijing, P.R. China.
J Environ Pathol Toxicol Oncol. 1995;14(3-4):159-63.
Apoptosis is a physiological phenomenon occurring during embryonic development, T and B cell maturation, and endocrine-induced atrophy. It can be initiated by various agents and has been considered to be related to the expression of the oncosuppressor p53 gene. In this review, p53 gene-targeting mice were used to study the effect of p53 gene status on the induction of apoptosis in bone marrow cells by gamma-ray irradiation. The results showed that homozygous null (p53 -/-) murine bone marrow cells were more resistant to the induction of apoptosis by radiation than other genotypes (heterozygous, p53 +/- and wild type, p53 +/+). The percentage of apoptotic cells in p53 +/+ mice was about three times that in p53 -/- mice at 4 hr after 6 Gy gamma-irradiation, and the analysis of the apoptosis-characteristic DNA ladder further supported these findings. We found that the homozygous null mice also can undergo apoptosis after irradiation. This suggested that there is another independent apoptotic p53 gene mechanism in irradiated murine bone marrow cells. Thus, in murine bone marrow cells, both p53 gene-dependent and -independent apoptosis occurred after irradiation. In our previous work, an increase in survival of hemopoietic progenitor cells after irradiation in vitro in p53 gene deletion mice was observed. This increase is closely related to the inhibition of apoptosis in bone marrow cells in p53 gene deletion mice.
细胞凋亡是一种在胚胎发育、T 细胞和 B 细胞成熟以及内分泌诱导的萎缩过程中发生的生理现象。它可由多种因素引发,并被认为与抑癌基因 p53 的表达有关。在本综述中,使用 p53 基因靶向小鼠来研究 p53 基因状态对γ射线照射诱导骨髓细胞凋亡的影响。结果表明,纯合缺失(p53 -/-)小鼠骨髓细胞比其他基因型(杂合子,p53 +/- 和野生型,p53 +/+)对辐射诱导的凋亡更具抗性。在 6 Gy γ射线照射后 4 小时,p53 +/+ 小鼠的凋亡细胞百分比约为 p53 -/- 小鼠的三倍,对凋亡特征性 DNA 梯带的分析进一步支持了这些发现。我们发现纯合缺失小鼠在照射后也能发生凋亡。这表明在照射的小鼠骨髓细胞中存在另一种独立于 p53 基因的凋亡机制。因此,在小鼠骨髓细胞中,照射后发生了 p53 基因依赖性和非依赖性凋亡。在我们之前的工作中,观察到 p53 基因缺失小鼠体外照射后造血祖细胞的存活率增加。这种增加与 p53 基因缺失小鼠骨髓细胞凋亡的抑制密切相关。