enng and Disease-Models--Animal

Topics: Animals; Carcinogens; Cell Transformation, Neoplastic; Disease Models, Animal; Epithelium; Gastric Mucosa; Humans; Methylnitronitrosoguanidine; Mice; Mucus; Precancerous Conditions; Rats; Stomach; Stomach Neoplasms

Gastric cancer results from a combination of Helicobacter pylori (H pylori) infection, exposure to dietary carcinogens, and predisposing genetic make-up. Because the role of these factors in gastric carcinogenesis cannot be determined readily in human beings, the present study examined the role of an oral carcinogen and H pylori infection in rhesus monkeys.. Gastroscopies were performed in 23 monkeys assigned to 4 groups: controls; nitrosating carcinogen ethyl-nitro-nitrosoguanidine administration alone; inoculation of a virulent H pylori strain alone (H); and ethyl-nitro-nitrosoguanidine in combination with H pylori (EH). Follow-up gastroscopies and biopsies were performed at 3-month intervals for 5 years for pathologic and molecular studies.. Postinoculation, H and EH groups showed persistent infection and antral gastritis. Starting at 2 and 5 years, respectively, gastric intestinal metaplasia and intraepithelial neoplasia developed in 3 EH monkeys but in no other groups. Transcriptional analysis of biopsy specimens at 5 years revealed group-specific expression profiles, with striking changes in EH monkeys, plus a neoplasia-specific expression profile characterized by changes in multiple cancer-associated genes. Importantly, this neoplastic profile was evident in nonneoplastic mucosa, suggesting that the identified genes may represent markers preceding cancer.. Gastric intraglandular neoplasia is induced in primates when H pylori infection is associated with consumption of a carcinogen similar to the nitrosamines found in pickled vegetables, suggesting that H pylori and the carcinogen synergistically induce gastric neoplasia in primates.

Topics: Animals; Biopsy; Carcinogens; Carcinoma in Situ; Cell Transformation, Neoplastic; Cluster Analysis; Diet; Disease Models, Animal; Disease Progression; DNA Repair; Female; Gastritis; Gastroscopy; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Helicobacter Infections; Helicobacter pylori; Macaca mulatta; Male; Metaplasia; Methylnitronitrosoguanidine; Oligonucleotide Array Sequence Analysis; Precancerous Conditions; Stomach Neoplasms; Time Factors

Effects of tamoxifen (TAM) on development of uterine endometrial carcinogenesis were studied in intact and ovariectomized (OVX) mice initiated with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). In experiment I, animals were implanted with cholesterol (ChL, controls) or TAM (5% w/w) and/or 17beta-oestradiol (E(2), 0.5% w/w) pellets s.c. from 9 to 25 weeks of age, until the termination of the experiment, and all received a single intra-uterine administration of ENNG (12.5 mg/kg) at 10 weeks of age. They were divided into four groups: ENNG + ChL (control), ENNG + TAM, ENNG + E(2) and ENNG + TAM + E(2). Endometrial proliferative lesions (hyperplasias and/or carcinomas) were observed in all groups, the incidences in the TAM- and/or E(2)-treated groups being two times higher than in the ChL-treated control animals. High induction (11/20, 55%) of adenocarcinomas was observed in the E(2) group but this was significantly decreased in combination with TAM (2/20, 10%), no carcinomas being found in the TAM group. In experiment II, animals pre-treated with TAM (10 weeks) and receiving E(2) post-treated (4 weeks) developed adenocarcinomas, although no cancers were observed in mice treated by ChL instead of TAM. In animals pre-treated with TAM and post-treated with ChL or TAM, no adenocarcinomas were also developed. In OVX mice (experiment III), proliferative lesions were observed in the TAM- and/or E(2)-treated groups, at incidences significantly higher than in ChL-treated animals, in which these lesions were completely absent. However, no adenocarcinomas were found, only slight hyperplasias being observed in the TAM group, although the incidence of adenocarcinoma was highest in the E(2) alone group, and significantly decreased in combination with TAM, as in experiment I. These results indicate that TAM may itself exert promotion effects, while exhibiting an anti-progression influence on uterine carcinogenesis in adult mice initiated by ENNG and receiving E(2).

Topics: Animals; Carcinogenicity Tests; Carcinogens; Disease Models, Animal; Drug Interactions; Endometrial Neoplasms; Female; Incidence; Methylnitronitrosoguanidine; Mice; Tamoxifen; Uterine Neoplasms

Rebamipide is a potent antioxidative agent; it increases gastric mucosal PGE2 production and thus protects the gastric mucosa. We hypothesized that the mechanisms of ulcer formation could be extended to carcinogenesis and that an increase in gastric mucosal protection may result in a decrease in gastric carcinogenesis. Therefore, we assessed the inhibitory effects of rebamipide on N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) -induced carcinogenesis in mice. The percentage of tumor-bearing mice in three treatment groups--ENNG + rebamipide 20 mg, ENNG + rebamipide 50 mg, and ENNG alone--was 55%, 42%, and 67%, respectively. The incidence of tumorigenesis tended to decrease with increasing doses of rebamipide. The difference between ENNG + rebamipide 50 mg and ENNG alone was statistically significant (P < 0.05). These results suggest that rebamipide may strengthen the host defense mechanisms related to carcinogenesis in the digestive tract.

Topics: Alanine; Animals; Antineoplastic Agents; Carcinogens; Disease Models, Animal; Dose-Response Relationship, Drug; Duodenal Neoplasms; Male; Methylnitronitrosoguanidine; Mice; Mice, Inbred C57BL; Quinolones

Current experimental models of pancreatic cancer either fail to reproduce the ductal phenotype or cause simultaneous cancers in other organs also. To develop an animal of pancreatic cancer that accurately mimics the human condition, we restricted carcinogenic exposure to the pancreas and specifically targeted ductal epithelial cells. Three different carcinogens were either implanted directly into the pancreas or infused into the pancreatic duct, with or without near-total pancreatectomy (as a means of inducing pancreatic ductal cell proliferation).. Groups of male Sprague-Dawley rats were exposed to varying doses of dimethylbenzanthracine (DMBA), methynitronitrosoguanidine, or ethylnitronitrosoguanidine either through direct implantation into the pancreas or infusion into the pancreatic duct. Near-total pancreatectomy was added in all groups except two DMBA implantation groups. Surviving rats were killed at 3, 6, 9, or 12 months, and the pancreata were evaluated histologically.. All three carcinogens caused pancreatic inflammation, ductal hyperplasia, atypia, and dysplasia beginning by 3 months and becoming more prominent at later time points. Only DMBA caused frequent invasive pancreatic ductal adenocarcinoma, which was first evident by 6 months. The prevalence of pancreatic cancer among DMBA-treated rats evaluated after 10 months was 39% (19 of 49). The addition of pancreatic resection did not enhance pancreatic cancer development.. Of the strategies tested, only direct implantation of DMBA into the rat pancreas frequently produces pancreatic cancer histologically similar to human ductal adenocarcinoma. The development of hyperplastic, atypical, and dysplastic changes preceding and accompanying carcinomas suggests that these lesions are preneoplastic. This model recapitulates the progression from normal to neoplastic epithelium and is likely to be useful for the study of morphologic and molecular mechanisms underlying the early stages of pancreatic carcinogenesis and for the investigation of novel diagnostic and therapeutic techniques.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Carcinoma, Ductal, Breast; Disease Models, Animal; Fibrosarcoma; Hyperplasia; Male; Methylnitronitrosoguanidine; Pancreatectomy; Pancreatic Ducts; Pancreatic Neoplasms; Rats; Rats, Sprague-Dawley; Sarcoma, Experimental

Sequential endoscopic observation of dog colons was performed during colon carcinogenesis. Two beagle dogs were given suppositories containing N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) every day for five months. In month 3, aberrant crypt foci (ACF), a putative preneoplastic lesion, were found in the colons of both dogs, but not in an untreated dog. The frequency of ACF increased until month 10, and then decreased. In month 9, very small lesions, less than 1 mm in diameter, which were similar to human early flat tumors, were first noticed. One of these lesions grew to about 7 mm in size without a change in its shape for 10 months. There were more than ten flat-type tumors in the two dogs, but such lesions were not found in the untreated dog. By biopsy, two of the lesions were proved to be well-differentiated adenocarcinomas histologically. Four polypoid lesions were found in one of the carcinogen-treated dogs. Thus, flat-type adenocarcinomas were induced in the dog colon by ENNG, and their development was followed by magnifying endoscopy.

Topics: Adenocarcinoma; Animals; Carcinogens; Colon; Colonic Neoplasms; Colonic Polyps; Disease Models, Animal; Dog Diseases; Dogs; Endoscopy; Methylnitronitrosoguanidine; Precancerous Conditions

It may be useful to study the incipient phase and growth behavior of pancreatic cancer if experimental pancreatic carcinoma can be produced in dogs. Twelve mongrel dogs were used. Pancreatography was done every month. N-nitrosobis (2-oxopropyl) amine (BOP) was administered through the drainage tube inserted into the dorsal pancreatic duct in 4 dogs. Macroscopically, atrophy of the pancreas was recognized, but microscopically, no tumors were observed. BOP was injected intraperitoneally in 2 dogs. No tumors were found, and the hepatic necrosis was detected in one dog. N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) was administered into the dorsal pancreatic duct in 2 dogs. Macroscopically, atrophy of the pancreas was recognized, but microscopically, no tumors were observed. ENNG was administered through the drainage tube inserted into the tail portion in 4 dogs. In one dog received a total dose of 595mg of ENNG, duct obstruction was detected by pancreatography and duct adenocarcinoma microscopically was found. Papillary hyperplasia of the epithelium of pancreatic duct was observed in all others. Pancreatic duct adenocarcinoma and papillary hyperplasia were successfully produced in dogs by intraductal administration of ENNG through the pancreatic tail portion. This method seems to be useful for producing experimental pancreatic cancer.

Topics: Adenocarcinoma; Animals; Disease Models, Animal; Dogs; Female; Male; Methylnitronitrosoguanidine; Nitrosamines; Pancreatic Ducts; Pancreatic Neoplasms

Topics: Adenocarcinoma, Mucinous; Animals; Disease Models, Animal; Dogs; Female; Gastric Mucosa; Male; Metaplasia; Methylnitronitrosoguanidine; Stomach Neoplasms

We prepared a suppository containing 50 mg of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG), and successfully produced experimental colon cancer with good reproducibility by continuous intrarectal insertion of one or two suppositories per day in dogs. The tumors were very similar to human colon cancers, macroscopically and histologically. In one of three dogs subjected to histopathological study, metastases to the lymph nodes, lung, liver and kidney were observed. This animal model produced by a simple procedure will be helpful in investigating treatment of rectal cancer.

Topics: Adenocarcinoma; Animals; Carcinoma; Colonic Neoplasms; Disease Models, Animal; Dogs; Lymphatic Metastasis; Methylnitronitrosoguanidine; Neoplasms, Experimental; Time Factors