The role of reduced expression of glutathione peroxidase gene on the development and progression of hepatocellular carcinoma

Long-Evans Cinnamon（LEC）大鼠是一种突变品系，其中肝炎和肝癌以极高的速率自发发展。我们观察到LEC大鼠和p53基因敲除小鼠肝脏细胞谷胱甘肽过氧化物酶（GSH-Px）活性显著降低。为了确定GSH-Px启动子是否被p53激活，进行liciferase测定。GSH-Px启动子在野生型和突变型p53细胞中均被激活，表明GSH-Px启动子受p53 N端激活结构域的激活。为探讨硒依赖型谷胱甘肽过氧化物酶（GSH-Px）在遗传性肝炎发病中的作用，我们比较了补硒和缺硒饲料喂养的LEC大鼠急性肝炎的发病率和分级。我们发现，硒缺乏的状态和由此产生的GSH-Px缺乏症并不促进肝炎，而是有抑制作用的LEC大鼠肝炎的发展。

The Long-Evans Cinnamon (LEC) rat is a mutant strain in which hepatitis and liver cancer spontaneously develop at extremely high rates. We observed marked reduction in the activity of cellular glutathione peroxidase (GSH-Px) in the liver of LEC rats and p53 knockout mice. To determine whether GSH-Px promoter is activated by p53, liciferase assay was performed. Activation of GSH-Px promoter was found in both cell llines expressing wild-type p53 and mutant p53, indicating that GSH-Px promoter is activated by N-terminal activation domain of p53. To investigate the role of selenium-dependent GSH-Px in the development of hereditary hepatitis, we compared incidences and grades of acute hepatitis between the LEC rats fed with seleniumm-supplemented diet and selenium-deficient diet. We found that selenium-deficient status and resultant GSH-Px deficiency does not promote hepatitis but rather have an inhibitory effect on the development of hepatitis in LEC rats.