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

为了阐明CNP（一种除草剂）在胆囊癌发病机制中的作用，我们研究了长期给药CNP对仓鼠的影响以及CNP排泄到人胆汁中的可能性。1.动物实验：用含CNP 2000ppm的饲料喂养40周：胆囊和胰管粘膜均未见致癌作用。CNP在BOP （n -亚硝基-双-（2-氧丙基）胺）实验致癌模型中的促进作用。胆囊黏膜严重发育不良发生率与对照组相当。胆囊癌发生率虽低（1/9），但只有实验组出现胆囊癌。2 .实验组胰腺癌或严重不典型增生的发生率高于对照组，但差异无统计学意义。CNP在实验成岩作用中的作用。在谷村的高糖饮食中添加浓度为2000ppm的CNP 20周后，对胆囊粘膜和胰管没有影响。二、人胆汁的研究：胆石症患者胆汁的致突变性。新泻地区患者胆汁的致突变性显著高于高知县患者，高知县胆道癌死亡率较低。CNP在人胆汁中的排泄两例胆结石患者的胆汁气相色谱分析显示强烈提示CNP排泄的模式。评论：动物实验结果没有显示CNP有任何致癌活性的证据。然而，促进活动被认为是极有可能的。结果表明，新泻地区胆汁的高诱变性可能与胆汁分泌的CNP有关。停止服用CNP后，应观察胆汁中CNP排泄模式和致突变性的变化。

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.