权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Study on the mechanism of the carcinogenesis of the biliary tract.

胆道癌变机制的研究。

基本信息

批准号：
01570760
负责人：
MIYAZAKI Kohji
金额：
$ 1.41万
依托单位：
Saga Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

Anomalous pancreaticobiliary duct union and presence of stones or parasites in ttie biliary tract are well-known high risk groups of biliary tract cancers, liowever, the mechanisms of the carcinogenesis have not been elucidated. Since most of the chemicals are metabolized in the liver, biliary epithelium are firstly and directly exposed to the activated carcinogens if they are ingested. Nevertheless the incidence of the biliary tract cancer is not so high as supposed. One of the reasons may be the rapid excretion of bile through biliary tract to the duodenum in disease free state, which makes the exposure time to the carcinogens too short for the epithelial DNA to be itijured. In the high risk groups bile stasis makes the exposure time lorig enough for DNA injury. In addition bile stasis should increase the cell cycle of the biliary epithelium by induction of the cell degeneration and the regeneration. We supposed that the increase in the cell cycles makes the chance of DNA injury enhanced. In the present study we investigated the modulators of cell cycle and the effect of the increase in the cell cycle on DNA injuries by the use of primary gallbladder epithelial cell culture/ in situ nick translation model. EGF and lithocholic acid increased the BrdU labeled cells and DNA injuries by MNNG were significantly enhanced by the presence of EGF arid/or lithocholic acid. Thus our hypothesis that the increase in the cell cycle as occurred iii the high risk groups enhances the chance of DNA injury which must be the first step of carcinogenests has been verified. The roles of sex hormones, cholesterol and/or other bile acids are now on study.

胰胆管合流异常和胆道结石、胆道寄生虫是胆道癌的高危人群，其发生机制尚未阐明。由于大多数化学物质在肝脏中代谢，因此如果摄入活化的致癌物，胆管上皮首先直接暴露于活化的致癌物。然而，胆道癌的发病率并没有想象中的那么高。其原因之一可能是胆汁在无病状态下经胆道迅速排泄到十二指肠，使接触致癌物的时间太短，以致上皮DNA不受损伤。在高危人群中，胆汁淤积使暴露时间过长，足以造成DNA损伤。胆汁郁积还可通过诱导胆管上皮细胞变性和再生，使细胞周期延长。我们推测细胞周期的增加使DNA损伤的机会增加。在本研究中，我们研究了细胞周期的调节剂和细胞周期的增加对DNA损伤的影响，通过使用原代胆囊上皮细胞培养/原位缺口平移模型。EGF和石胆酸可增加BrdU标记的细胞数，且EGF和/或石胆酸可明显增强MNNG对DNA的损伤作用。因此，我们的假设，即在高危人群中发生的细胞周期的增加增加了DNA损伤的机会，这一定是致癌的第一步已经得到证实。性激素、胆固醇和/或其他胆汁酸的作用正在研究中。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

宮崎耕治,呂明徳,堤宣翁,永渕一光,中野修治,中山文夫: "培養胆道上皮細胞を用いた新しい胆道癌発癌物質検出法:アルカリ溶出法によるDNA一本鎖切断検出" 日本消化器病学会雑誌. 86. 2541-2544 (1989)

Koji Miyazaki、Meitoku Ro、Nobuo Tsutsumi、Kazumitsu Nagabuchi、Shuji Nakano、Fumio Nakayama：“使用培养的胆道上皮细胞检测胆道癌致癌物的新方法：通过碱性洗脱法检测 DNA 单链断裂”《日本胃肠病学杂志》日本医学会。86。2541-2544（1989）