methylnitronitrosoguanidine and Bile-Duct-Neoplasms

The modifying effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a mutagenic by-product in chlorinated water, on the development of glandular stomach cancers were investigated in Wistar rats. A total of 120 males, 6 weeks of age, were divided into six groups. After initiation with 100 ppm N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) solution and 5% NaCl diet for 8 weeks, 30 rats each in groups 1-3 were given MX in the drinking water at concentrations of 30, 10, or 0 ppm for the following 57 weeks. Ten animals each in groups 4-6 were administered the MX without prior carcinogen exposure. There were no statistical significant differences in final body weights between the groups. The incidences and multiplicities of adenocarcinomas in the glandular stomachs were significantly higher (P < 0.05) in the initiated 30 ppm MX group than those in the MNNG/NaCl group. The incidences of atypical hyperplasias in the glandular stomachs were also significantly increased (P < 0.05 or 0.01) by the MX treatments. With their multiplicity, the effects were clearly dose dependent. Interestingly, the 30 ppm MX alone itself induced atypical hyperplasias in the pylorus, although the incidences and severity were low. Moreover, MX showed a tendency to enhance the development of intrahepatic cholangiocellular tumors and thyroid follicular cell tumors in the MNNG-treated animals. The results of the present study thus indicate that MX exerts promoting effects when given during the postinitiation phase of two-stage glandular stomach carcinogenesis in rats.

Topics: Adenocarcinoma; Adenocarcinoma, Follicular; Adenoma, Bile Duct; Animals; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Body Weight; Carcinogens; Cholangiocarcinoma; Cocarcinogenesis; Fibrosis; Furans; Hyperplasia; Male; Methylnitronitrosoguanidine; Mutagens; Organ Size; Precancerous Conditions; Pylorus; Rats; Rats, Wistar; Stomach; Stomach Diseases; Stomach Neoplasms; Thyroid Neoplasms; Water Pollutants, Chemical

Topics: Adenocarcinoma; Adenocarcinoma, Papillary; Animals; Bile Duct Neoplasms; Dogs; Female; Male; Methylnitronitrosoguanidine; Neoplasm Invasiveness; Neoplasms, Experimental

The present study was designed to produce the experimental carcinoma of the biliary tract in dogs. Tube cholecystostomy was constructed in 8 mongrel dogs and 5-10 ml of 0.7-1.0 mg/ml solution of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) was administered through the tube every day for the maximum period of 180 days. As the results: The experiment had to be cut off in 7 dogs (5 dogs: The tube was inadvertently pulled out. 2 dogs: died of general weakness). Pathological changes were observed in one dog given ENNG for 180 days and sacrificed at 372 days after the beginning of the experiment. Macroscopically, scattered foci of flat elevation of the mucosa were observed in the entire mucosal surface of common bile duct and a tiny polypoid lesion at the terminal protion. A tiny polypoid projection was adenocarcinoma confined to the mucosa, and areas of flat elevation showed marked hyperplasia of mucosa with partial atypical proliferation. No remarkable findings were noted in other organs.

Topics: Adenocarcinoma; Animals; Bile Duct Neoplasms; Common Bile Duct; Dogs; Female; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Nitrosoguanidines