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

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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.