Chemopreventative effect of hochu-ekki-to (TJ-41) on chemically induced biliary carcinogenesis in hamsters.
BACKGROUND
Bilioenterostomy is a common surgical technique that is widely used. Recently, clinical studies have revealed that biliary carcinomas can occur after bilioenterostomy. The present study was designed to evaluate whether hochu-ekki-to (TJ-41), a Japanese herbal drug, could prevent chemically induced biliary carcinomas in bilioenterostomized hamsters.


METHODS
Syrian golden hamsters were subjected to choledochojejunostomy and then received subcutaneous injections of N-nitrosobis(2-oxopropyl) amine every 2 weeks at a dose of 10 mg/kg. N-nitrosobis(2-oxopropyl) amine administration was started 4 weeks after surgery. The animals were simultaneously p.o. administered TJ-41 in water every day at a dose of 1000 mg/kg (TJ-41 group). The control hamsters were administered water alone. The hamsters were sacrificed 22 weeks after surgery, and the development of biliary carcinomas, the presence and degree of cholangitis, and the cell kinetic status of the biliary epithelium were evaluated histologically.


RESULTS
Intrahepatic bile duct carcinomas developed in 15/17 (88%) hamsters in the control group and in only 8/17 (47%) hamsters in the TJ-41 group (P < 0.05). The degree of cholangitis was not different between the two groups. However, the proliferating cell nuclear antigen labeling index of the biliary epithelium in the TJ-41 group (6.46%) was significantly lower than the controls (9.67%) (P < 0.05). These findings indicated that TJ-41 reduced accelerated biliary epithelial cell kinetics after bilioenterostomy, resulting in the prevention of carcinogenesis.


CONCLUSIONS
TJ-41 has a preventive effect on chemically induced carcinoma of the biliary tract after bilioenterostomy.
Tsuneoka
Noritsugu
N
Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. noritugu@xd5.so-net.ne.jp
Tajima
Yoshitsugu
Y
Kitasato
Amane
A
Fukuda
Kenzo
K
Kitajima
Tomoo
T
Adachi
Tomohiko
T
Mishima
Takehiro
T
Kuroki
Tamotsu
T
Onizuka
Shinya
S
Kanematsu
Takashi
T
D000818:Animals; D001650:Bile Duct Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002768:Choledochostomy / Q000009:adverse effects; D006224:Cricetinae; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D007279:Injections, Subcutaneous; D008647:Mesocricetus; D009602:Nitrosamines; D008517:Phytotherapy / Q000379:methods*
D004365:Drugs, Chinese Herbal; D009602:Nitrosamines; C402943:bu-zhong-yi-qi-tang; C013622:nitrosobis(2-oxopropyl)amine