Production of hepatoma in cirrhotic liver and its prediction

动物实验1.大鼠肝硬化的实验性制作连续口服硫代乙酰胺（TAA），24周后大鼠肝硬化形成。1）缺口平移法显示，大鼠肝硬化肝细胞DNA损伤，并随TAA给药时间的延长而加重。2）在上述肝损伤模型中，用BrdU处理后，用流式细胞术检测DNA，用标记指数法检测细胞周期。结果表明，TAA给药后第3周和第16周肝细胞周期增加，而在第24 - 32周肝硬化形成时，肝细胞周期下降。也就是说，再生结节没有显示出细胞周期的特别增加。胆管上皮细胞周期高峰出现早于肝细胞。第24天标记指数很高，即所谓的胆管纤维化--即癌前状态。从这些结果可以看出，大鼠肝硬化不会发展成肝癌。3）研究了引发剂在肝硬化肝癌发生中的重要性。作为癌症引发剂，二乙基亚硝胺（DEN）仅给药一次，TAA如上所述给药。与DEN和TAA单独处理的大鼠相比，该模型的细胞周期增加。同时，在再生结节中也有许多肝细胞呈G GTP癌特异性酶阳性，提示该指标虽然只有一次，但在肝癌的癌变过程中是非常重要的

I Animal experiments1. Experimental production of hepatic cirrhosis in ratContinuous oral administration of thioacetamide (TAA) was performed in rats, and liver cirrhosis was produced after 24 weeks.1) DNA damage of cirrhotic hepatocytes was revealed by nick translation method, and becomes increasingly serious with the prolongation of TAA administration. The DNA damage was supposed to have some relationship with carcinogenic gene( c-myc ).2) In the cirrhotic liver above-mentioned, DNA analysis by the flow cytometry and cll cycle by labeling index after BrdU administration. As the results, hepatocyte cell cycle increase at 3rd and 16th week after TAA administration, however, it decreases at 24th - 32nd week, when the liver cirrhosis was established. That is, the regeneration nodule shows no particular increase of cell cycle. As to bile duct epithelium, the peak of cell cycle appeared earlier than in hepatocyte. The labeling index at 24th was very high, when the so-called cholangio-fibrosis -- alleged as the precancerous state. From these results, liver cirrhosis in rat dose not develop into hepatoma.3) Importance of initiator in production of hepatoma in cirrhosis was studied. As the cancer initiator, diethylnitrosamine( DEN ) was administrated only once and TAA was administered as mentioned above. The cell cyle increases in this model comparing with the rats treated with DEN alone and TAA alone. At the same time, there were many hepatocyte which revealed positive G GTP Cancer specific enzyme, in regenerating nodules.These results indicates that indicator, although only one time, is very important in carcinogenesis of hepatoma in cifrhosis