enng and Cell-Transformation--Neoplastic

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

The cell kinetic alteration in the background mucosa of canine gastric cancer induced by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) was evaluated by cytofluorometry in which the rate of S and G2 + M phase cell in gastric mucosal cells could be calculated, and a triphasic alteration was demonstrated; an initial reduction phase, an increase phase and a plateau phase with a high value. The initial reduction phase was caused by non-specific toxicity of ENNG as observed in drug induced gastric mucosal lesions, and subsequent increase and plateau phases originated from the action of ENNG itself to activate the mucosal turn-over and from histological changes in the background mucosa such as regenerative hyperplastic change after mucosal erosion and atrophic changes, sometimes including intestinal metaplastic change. Further, in comparison to carcinogenesis in chemically induced gastric cancer with and without a surfactant (Tween 60), it was suggested that one of the promotion effects of Tween 60 was closely related with activation of the mucosal turn-over.

Topics: Adenocarcinoma, Mucinous; Animals; Cell Cycle; Cell Transformation, Neoplastic; DNA, Neoplasm; Dogs; Flow Cytometry; Gastric Mucosa; Gastroscopy; Male; Methylnitronitrosoguanidine; Polysorbates; RNA, Neoplasm; Stomach Neoplasms

An endoscopical study of chronological change during the carcinogenetic process of cancer of the esophagus induced by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) in 16 male beagle dogs was performed to clarity whether or not precancerous lesions exist in the esophagus. Redness was first observed in the mucosa in the lower and/or middle portions of the esophagus. A small nodule developed in the redness, followed by a nodule. The nodule then developed into a flat polyp which finally developed into lesions such as an elevated lesions, protrusions or elevations with depressions. Histologically, esophagitis or acanthosis in the redness and acanthosis were found in most of the small nodules. With regard to the nodules, papillomatosis was observed in half of the lesions, while either acanthosis or atypical epithelial proliferation were found in most of the flat polyps. Almost all the elevated or protruding lesions were found to be carcinoma.

Topics: Animals; Biopsy; Carcinogens; Cell Transformation, Neoplastic; Dogs; Esophageal Neoplasms; Esophagoscopy; Esophagus; Male; Methylnitronitrosoguanidine