Production of hepatoma in cirrhotic liver and its prediction

1.动物实验大鼠连续口服硫乙酰胺（TAA）， 24周后产生肝硬化。1)缺口翻译法显示肝硬化肝细胞DNA损伤，且随着TAA给药时间的延长，DNA损伤日益严重。DNA损伤与致癌基因（c-myc）有关。2)上述肝硬化患者给予BrdU后流式细胞仪DNA分析和细胞周期标记指数。结果表明，肝细胞周期在TAA给药后第3周和第16周增加，而在第24 - 32周肝硬化建立时减少。即再生结节未表现出细胞周期的明显增加。胆管上皮细胞周期高峰出现时间早于肝细胞。标记指数在24是非常高的，当所谓的胆管纤维化-所谓的癌前状态。由此可见，大鼠肝硬化不会发展为肝癌。3)探讨了引发剂在肝硬化肝癌发生中的重要作用。作为癌症引发剂，二乙基亚硝胺（DEN）只给药一次，TAA按上述方法给药。与单用DEN和TAA治疗的大鼠相比，该模型的细胞周期明显延长。同时，再生结节中有许多肝细胞显示GTP癌特异酶阳性。这些结果表明，该指标虽然只有一次，但在肝硬化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