| 共同演者 |
Hikita Hayato（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Saito Yoshinobu（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Kawaguchi Tsukasa（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Shimizu Satoshi（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Shigekawa Minoru（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Kodama Takahiro（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Li Wei（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Sakamori Ryotaro（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Miyagi Takuya（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Kanto Tatsuya（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Hiramatsu Naoki（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Tatsumi Tomohide（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan）, Takehara Tetsuo（Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan） |
| 抄録 |
Background and Aim：Apoptosis serves as an important mechanism by removing DNA damaged-cells and is considered to inhibit carcinogenesis. On the other hand, hepatocyte apoptosis is a key feature of chronic liver disease including viral hepatitis and steatohepatitis, which are well-known risk factors for HCC. The present study examined the impact of apoptosis on liver carcinogenesis. Methods：We used male hepatocyte-specific KO mice of Mcl-1,one of anti-apoptotic protein, as a model of apoptosis-prone liver. To induce DNA damage and develop HCC, mice were intraperitoneally administered 20 mg diethylnitrosamine（DEN）/kg at the age of 2 weeks. Results：Spontaneous hepatocyte apoptosis in Mcl-1 KO mice liver was confirmed biochemically by serum ALT levels and serum caspase-3/7 activity, and histologically by TUNEL staining of liver sections. At the age of 6 months, while neither wild-type mice nor Mcl-1 KO mice without DEN showed any HCCs in their livers, 15.4%（2/13）of wild-type mice administrated DEN induced HCC. In sharp contrast with wild-type mice, DEN induced HCC in 100%（5/5）of Mcl-1 KO mice. The average of their maximum HCC size was 11.4mm, compared with 6.5mm in wild-type mice. Their incidence rate, tumor total volume and the number of tumors were significantly higher than those of wild-type mice. Conclusion：Hepatocyte apoptosis promotes oncogenic potential and inhibition of apoptosis may be useful for preventing liver carcinogenesis. |
