Role of CNP (a herbicide) on the pathogenesis of carcinoma of the gallbldder.

CNP（一种除​​草剂）在胆囊癌发病机制中的作用。

• 批准号: 05454375
• 负责人: YOSHIDA Keisuke
• 金额: $ 1.98万
• 依托单位: The Nippon Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454375/
• 关键词: CNP; Gallbladder cancer; 胆汁変異原性

To clarify the role of CNP (a herbicide) in the pathogenesis of the gallbladder cancer, effects of long term administration of CNP to hamsters and the possibility of CNP excretion into the human bile were investigated.I : Animal experiments :1. Feeding on CNP 2000ppm containing diet for 40 weeks : No carcinogenic effect was observed on the mucosa either of the gallbladder or of the pancreatic duct.2. Promoting effect of CNP in the experimental carcinogenesis model using BOP (N-nitroso-bis- (2-oxypropyl) amine). Incidence of sever dysplasia in the gallbladder mucosa was equal to that of the control group. Gallbladder cancer was observed only in the experimental group even though the incidence was low (1/9). Incidence of carcinoma or sever dysplasia in the pancreas was higher in the experimental group even though the difference not statistically significant.3. Effects of CNP in the experimental lithogenesis. Addition of CNP in the concentration of 2000ppm to the Tanimura's high glucose diet for 20 weeks showed no effect on the mucosa of the gallbladder nor of the pancreatic duct.II : Study on the human bile :1. Mutagenicity of the bile of patients with cholelithiasis. Mutagenicity of the bile from patients living in Niigata region was significantly higher than that of patients living in Kochi where the mortality rate by the biliary carcinomas was low.2. Excretion of CNP in the human bile. Gas chromatographic analysis of the bile of two patientss with cholelithiasis showed the pattern strongly suggestive of excretion of CNP.Commnet : Results of animal experiments did not show any evidence of carcinogenic activity of CNP.However, promoting activity was considered highly possible. It was strongly suggested that CNP excreted into the bile playd an role in the high mutagenicity of the bile in Niigata region. Changes in CNP excretion pattern and mutagenicity of the bile after the cessation of CNP consumption should be followed.

为了阐明CNP（一种除草剂）在胆囊癌发病机制中的作用，研究了长期给予CNP对仓鼠的影响以及CNP排泄到人胆汁中的可能性。饲喂含CNP 2000 ppm的饲料40周：对胆囊和胰管粘膜均无致癌作用. CNP在使用BOP（N-亚硝基-双-（2-氧丙基）胺）的实验性致癌模型中的促进作用。胆囊粘膜重度异型增生发生率与对照组相当。胆囊癌仅在实验组中观察到，尽管发病率较低（1/9）。实验组胰腺癌或重度异型增生发生率高于对照组，但差异无统计学意义. CNP在实验性结石形成中的作用在谷村高糖饲料中添加浓度为2000 ppm的CNP 20周，对胆囊粘膜和胰管粘膜均无影响。胆石症患者胆汁的致突变性。来自新泻地区患者的胆汁的致突变性显著高于来自高知地区患者的致突变性，因为高知地区胆管癌的死亡率较低. CNP在人胆汁中的排泄。对两名胆石症患者胆汁的气相色谱分析显示，CNP的排泄模式强烈暗示CNP的排泄。评论：动物实验结果未显示CNP具有致癌活性的任何证据。然而，促进活性被认为是高度可能的。这强烈表明，分泌到胆汁中的CNP在新泻地区胆汁的高致突变性中起作用。应跟踪CNP排泄模式的变化和停用CNP后胆汁的致突变性。

项目成果

Hiroshi Mano, Masaharu Yamamoto, Juan Carlos Araya, Kiyoshi Kato, Mitsuhiro Tsutsui, Tatsuo Ohta, Keisuke Yoshida, Hideo Kinebuchi and Hikoya Hayatsu: "Mutagenicity of blue rayon extracts of human bile in the Ames test." Mutation Research.Volume 290. 303-

Hiroshi Mano、Masaharu Yamamoto、Juan Carlos Araya、Kiyoshi Kato、Mitsuhiro Tsutsui、Tatsuo Ohta、Keisuke Yoshida、Hideo Kinebuchi 和 Hikoya Hayatsu：“艾姆斯试验中人胆汁蓝色人造丝提取物的致突变性。”

Hiroshi Mano: "Mutagenicity of blue rayon extracts of human bile in the Ames test" Mutation Research. 290. 303-309 (1993)

Hiroshi Mano：“艾姆斯试验中人胆汁蓝色人造丝提取物的致突变性”突变研究。

吉田 奎介: "胆道癌切除例に対する補助免疫化学療法-新潟地区多施設共同研究による検討-" 新潟医学会雑誌. 108. 249-256 (1994)

Keisuke Yoshida：“胆道癌切除病例的辅助免疫化疗 - 基于新泻地区多中心联合研究的研究”新泻医学会杂志 108. 249-256 (1994)。

吉田,奎介: "胆嚢・胆管癌切除材料の取扱い(2)" 臨床外科. 48. 54-58 (1993)

吉田圭介：“胆囊/胆管癌切除材料的处理（2）”《临床外科》48. 54-58（1993）。