p53基因缺陷小鼠对青石棉纤维诱发间皮瘤的易感性。
Susceptibility of p53-deficient mice to induction of mesothelioma by crocidolite asbestos fibers.
作者信息
Marsella J M, Liu B L, Vaslet C A, Kane A B
机构信息
Department of Pathology and Laboratory Medicine, Brown University School of Medicine, Providence, RI 02912, USA.
出版信息
Environ Health Perspect. 1997 Sep;105 Suppl 5(Suppl 5):1069-72. doi: 10.1289/ehp.97105s51069.
Abstract
Exposure of mesothelial cells to asbestos fibers in vitro has been shown to induce DNA damage mediated by oxidants. An early cellular response to DNA damage is increased expression of the p53 protein. This protein induces transcription of genes that activate cell cycle checkpoints or induce apoptosis. A murine mesothelial cell line that spontaneously acquired a point mutation in the p53 gene shows increased sensitivity to DNA damage induced by crocidolite asbestos fibers. It is hypothesized that p53-deficient mice will show increased sensitivity to the genotoxic effects of asbestos and accelerated development of malignant mesotheliomas.
摘要
体外实验表明，间皮细胞暴露于石棉纤维会诱导由氧化剂介导的DNA损伤。细胞对DNA损伤的早期反应是p53蛋白表达增加。该蛋白可诱导激活细胞周期检查点或诱导细胞凋亡的基因转录。一种在p53基因中自发获得点突变的小鼠间皮细胞系，对青石棉纤维诱导的DNA损伤表现出更高的敏感性。据推测，p53基因缺陷的小鼠对石棉的遗传毒性作用将表现出更高的敏感性，并加速恶性间皮瘤的发展。
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