Study on Stress-response pathway in tumorigenesis in LEO rats that shows a high incidence of spontaneous liver cancer.

我们研究了LEC大鼠的应激反应途径，显示自发性肝癌的高发病率。虽然铜和离子积累在LEG大鼠的肝脏中的年龄依赖性的方式，铜积累诱导DNA链断裂，肝细胞，但铁的积累没有。雌性大鼠肝细胞中铜蓄积引起的DNA链断裂量并不比雄性大鼠多，但雌性大鼠肝损伤比雄性大鼠严重.用Trientine（一种特异性铜螯合剂）治疗LEG大鼠，可防止DNA链断裂的诱导，但肝脏中仍保留有高铜含量。木脂素是从亚麻中提取的苯丙素类衍生物，对CCl_4所致大鼠肝损伤具有保护作用。LEG大鼠胸腺细胞在体外培养和X射线照射过程中对诱导凋亡具有高度敏感性。LEG大鼠成纤维细胞呈高。UVB照射诱导细胞凋亡的敏感性。在LEG大鼠成纤维细胞系中，复制抑制诱导非凋亡性细胞死亡。我们发现DNA依赖性蛋白激酶Ku蛋白的核转位和积累在X射线诱导的大鼠细胞DNA双链断裂（DSB）修复中起重要作用，这些结果提示，DSB修复缺陷和应激反应途径的异常可能是导致LEG细胞损伤的重要原因之一。与LEG大鼠肝癌的高发病率相关。

We investigated a stress-responsive pathway in LEC rats that shows.a high incidence of spontaneous liver cancer.1. Although copper and ion accumulated in the liver of LEG rats in an age-dependent manner, copper accumulation induced DNA strand breaks in the, liver cells, but accumulation of iron did not. The amounts of DNA strand breaks produced by copper accumulation in the liver cells of female rats are not more abundant than those in the cells of male rats, although hepatic injury in female rats is more serious than in male rats.2. Treatment of LEG rats with trientine, a specific copper chelating agent, prevents the induction of DNA strand breaks, although high copper content still remain in the liver. Lignan, phenylpropanoid derivatives, prepared from flax showed protective effect on hepatic injury in rats induced by CCl_4.3. Thymocytes of LEG rats showed high sensitivities in induction of apoptosis during in vitro cultivation and X-irradiation. LEG rat fibroblasts showed high. sensitivity in induction of apoptosis by UVB irradiation. Inhibition of replication induced non-apoptotic cell death in LEG rat fibroblatst cell lines.4. We showed nuclear translocation and accumulation of Ku proteins, components of DNA-dependent protein kinase are important for repair of DNA double strand breaks (DSB) induced by X-irradiation in rat cells, and that there are some defects in maintaining the levels of Ku proteins in the nuclei of LEG rat cells.These results suggest that a deficiency of DSB repair and abnormality of some pathway responsive to a variety of stress may be associated with a high incidence of liver cancer of LEG rats.