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

胆道癌变机制的研究。

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570760/
• 关键词: Biliary tract cancer; Chemical carcinogenesis; Cell culture; DNA injury; Call cycle; In situ nick translation; ニックトランスレ-ション法; 胆嚢上皮細胞培養; コラ-ゲンマトリックス; ニックトランスレ-ション

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.

异常的胰腺导管结合和胆道中的石头或寄生虫的存在是众所周知的胆道癌的高风险基团，尚未阐明癌变的机制。由于大多数化学物质在肝脏中被代谢，因此胆汁上皮首先会直接暴露于活化的致癌物中。然而，胆道癌的发生率并不像预期的那样高。原因之一可能是胆汁通过胆道迅速排泄到无疾病状态下的十二指肠，这使得对癌素的暴露时间太短了，无法进行上皮DNA。在高风险组中，胆汁停滞使暴露时间lorig足以用于DNA损伤。另外，胆汁的暂停应通过诱导细胞变性和再生来增加胆道上皮的细胞周期。我们认为细胞周期的增加使DNA损伤的机会增加了。在本研究中，我们研究了细胞周期的调节剂以及细胞周期增加对DNA损伤的影响，通过使用原代胆囊上皮细胞培养/原位nick翻译模型。 EGF和岩性酸增加了BRDU标记的细胞，并且通过EGF干旱/或岩性酸会显着增强MNNG的DNA损伤。因此，我们的假设是，III的细胞周期增加增加了高风险组增加了DNA损伤的机会，DNA损伤的机会必须是癌变的第一步。性激素，胆固醇和/或其他胆汁酸的作用正在研究。

项目成果

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）

呂明徳,宮崎耕治,吉富聰一,中山文夫: "胆管上皮分離細胞を用いた胆道癌関連発癌物質の検出モデル" 日本外科学会雑誌. 90. 404-408 (1989)

Meitoku Lu、Koji Miyazaki、Soichi Yoshitomi、Fumio Nakayama：“使用分离的胆管上皮细胞检测与胆道癌相关的致癌物的模型”日本外科学会杂志 90. 404-408 (1989)。

宮崎 耕治他: "肝・胆道癌の研究における細胞培養" 組織培養. 17. 26-29 (1991)

Koji Miyazaki 等人：“肝癌和胆道癌研究中的细胞培养”组织培养。17. 26-29 (1991)

K.Miyazaki,K.Date,S.Imamura,Y.Ogawa,F.Nakayama: "Familial occurrence of anomalous pancreatiobiliary duct union associated with gallbladder neoplasms" Am.J.Gastroenterol.84. 176-181 (1989)

K.Miyazaki，K.Date，S.Imamura，Y.Okawa，F.Nakayama：“与胆囊肿瘤相关的异常胰胆管结合的家族性发生”Am.J.Gastroenterol.84。

宮崎 耕治: "胆道癌化学発癌物質検出のための培養胆道上皮細胞/アリカリ溶出法" 日本消化器病学会雑誌. 86. 2540-2544 (1989)

Koji Miyazaki：“培养胆道上皮细胞/Alikali洗脱法检测胆道癌中的化学致癌物”日本胃肠病学会杂志86。2540-2544（1989）。