| Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥5,600,000 (Direct Cost: ¥5,600,000)
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| Research Abstract |
I Animal experiments
1. Experimental production of hepatic cirrhosis in rat
Continuous 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
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