enng and Precancerous-Conditions

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

Sulpiride and ethylene glycol monomethyl ether (EGME) are known ovarian toxicants that stimulate prolactin (PRL) secretion, resulting in hypertrophy of the corpora lutea and increased progesterone (P4) production. The purpose of the present study was to investigate how the PRL stimulatory agents affected uterine carcinogenesis and to clarify the effects of PRL on endometrial adenocarcinoma progression in rats. Ten-week-old female Donryu rats were treated once with N-ethyl-N'-nitro-N-nitrosoguanidine (20 mg kg(-1) ), followed by treatment with sulpiride (200 ppm) or EGME (1250 ppm) from 11 weeks of age to 12 months of age. Sulpiride treatment inhibited the incidence of uterine adenocarcinoma and precancerous lesions of atypical endometrial hyperplasia, whereas EGME had no effect on uterine carcinogenesis. Sulpiride markedly prevented the onset of persistent estrus throughout the study period, and EGME delayed and inhibited the onset of persistent estrus. Moreover, sulpiride-treated animals showed high PRL and P4 serum levels without changes in the levels of estradiol-17β, low uterine weights and histological luteal cell hypertrophy. EGME did not affect serum PRL and P4 levels. These results suggest that the prolonged low estradiol-17β to P4 ratio accompanied by persistent estrous cycle abnormalities secondary to the luteal stimulatory effects of PRL may explain the inhibitory effects of sulpiride on uterine carcinogenesis in rats. Copyright © 2015 John Wiley & Sons, Ltd.

Topics: Adenocarcinoma; Animals; Anticarcinogenic Agents; Carcinogenesis; Carcinogens; Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Estrus; Ethylene Glycols; Female; Infertility, Female; Methylnitronitrosoguanidine; Organ Size; Ovary; Precancerous Conditions; Progesterone; Prolactin; Rats, Inbred Strains; Sulpiride; Uterus; Weight Gain

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

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

Signet-ring-cell carcinomas were induced in the stomach of 12 beagle dogs by p.o. administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG), and the morphology and modes of cell proliferation in an incipient stage of cancer growth were studied with bromodeoxyuridine (BrdUrd) incorporation. From 5 to 27 months after the completion of 8 months' carcinogen treatment, minute carcinomas were found in the stomachs of 9 dogs. Before sacrifice, the dogs were given a single or repeated i.v. injections of BrdUrd for 1-3 days. Minute signet-ring-cell carcinomas were found to form a layered structure, in which the cancer cells proliferated in the lamina propria at the gland-neck level and differentiated to postmitotic signet-ring cells at the upper and lower levels of the mucosa. From repeated injections of BrdUrd, the time required for all the proliferative cells to be labelled with BrdUrd (reflecting the maximum cell-cycle time) was estimated to be 1.7 days for the normal glands, and 2.7 days for minute signet-ring-cell carcinomas. From the labelling index with BrdUrd as well as from the morphology, earliest carcinomas were identified in the single gland. There remained atrophic normal epithelium commonly in the single-gland lesions. Proliferative atypical cells appeared to be shed into the stroma passively through the atrophy and subsequent collapse of the gland rather than through active invasion. This may be a reason why cancer cells in minute signet-ring cell carcinomas preserved the normal pattern of cell renewal movement to form the layered structure.

Topics: Adenocarcinoma, Mucinous; Alcian Blue; Animals; Bromodeoxyuridine; Cell Division; Dogs; Gastric Mucosa; Immunoenzyme Techniques; Methylnitronitrosoguanidine; Precancerous Conditions; Stomach Neoplasms

DNA content and nuclear area were measured by microspectrophotometry in gastric carcinogenesis of three adult wolfdogs induced by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). The mean values and standard deviations of DNA content and nuclear area in normal gastric mucosa were 10.03 +/- 2.30 AU and 28.76 +/- 5.85/microns2; those in atrophic gastritis were 12.04 +/- 3.34 AU and 28.69 +/- 8.02/microns2; in mild dysplasia 13.52 +/- 3.73 AU and 28.23 +/- 8.12/microns2; in moderate dysplasia 20.88 +/- 4.57 AU and 47.58 +/- 10.74/microns2; in severe dysplasia 24.01 +/- 4.48 AU and 56.64 +/- 12.53/microns2; in well-differentiated adenocarcinoma 33.07 +/- 9.38 AU and 72.99 +/- 15.57/microns. These figures were different (P less than 0.01). The nuclear area of gastric carcinoma increased with DNA content (r = 0.73, P less than 0.01). The distribution patterns of DNA content in the histogram showed that diploidy was decreased and polyploidy increased in cancer cells. These findings indicate that DNA ploidy patterns and nuclear area can be useful indices for differentiating carcinoma from precancerous lesions.

Topics: Animals; DNA, Neoplasm; Dogs; Methylnitronitrosoguanidine; Microspectrophotometry; Ploidies; Precancerous Conditions; Prospective Studies; Stomach Neoplasms

Intestinal metaplasia (IM) in the glandular stomach of male Wistar rats induced by oral administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) and/or intubation of 0.1N sodium hydroxide (NaOH) was studied as follows. Experiment I, sequential study: Rats in group I were given 100 micrograms/ml ENNG in drinking water for 12 weeks. Rats in group II were given 5 ml of 0.1N NaOH by gastric intubation once a week for 12 weeks. Group III control rats were given tap water. Rats were killed from week 1 until week 69 sequentially. IM was first found at week 26 in group I and at week 58 in groups II and III, its incidence being significantly higher in group I than in the other two groups (P less than 0.01), but without any difference between group II and group III. Experiment II, two-stage carcinogenesis: Rats in groups I and II were treated in the same way as in experiment I, while rats in group III were given 100 micrograms/ml ENNG for 12 weeks, followed by 0.1N NaOH once a week for 12 weeks intragastrically. All rats were killed at week 56. The numbers of metaplastic glands in groups I and III were higher than in group II. Gastric carcinomas were induced in all groups of rats treated with ENNG. The results of these two experiments show that IM is effectively induced by a carcinogen but is not enhanced by regeneration induced by alkaline treatment.

Topics: Aging; Animals; Carcinogens; Carcinoma; Gastric Mucosa; Male; Metaplasia; Methylnitronitrosoguanidine; Precancerous Conditions; Rats; Rats, Inbred Strains; Regeneration; Sodium Hydroxide; Stomach Neoplasms

Sequential quantitative analyses were made of pepsinogen 1 (Pg 1) decreased pyloric glands after treating male WKY rats first with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and then with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) as a second gastric carcinogen or sodium taurocholate (Na-TC) as a gastric promoter. Animals received a single dose of MNNG (160 mg/kg body weight) by gastric intubation followed two weeks later by either ENNG in drinking water (100 micrograms/ml) (group 1), basal diet containing 0.25% Na-TC (group 2), or basal diet and tap water (group 3), from weeks 3 to 24. Animals were sacrificed at weeks 8, 12, 16, 20 and 24. Sections of the pyloric mucosa were investigated for Pg 1 immunostaining. In comparison with group 3, induction of Pg 1 decreased pyloric glands was significantly enhanced by ENNG from week 8 and by Na-TC from week 16. The former exerted a significantly stronger effect at each time point. The results suggest that Pg 1 decreased pyloric glands represent a good marker for early detection of gastric carcinogens and promoters in in vivo test systems.

Topics: Animals; Carcinogens; Gastric Mucosa; Immunologic Techniques; Isoenzymes; Male; Methylnitronitrosoguanidine; Pepsinogens; Precancerous Conditions; Rats; Stomach Neoplasms; Taurocholic Acid