enng and Colonic-Neoplasms

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

An interposed colon segment has been clinically reconstructed as a gastric substitute. The purpose of this study is to establish a rat model of colonic interposition and to investigate serial mucosal changes and adaptation of interposed colon mucosa under prolonged exposure to bile and pancreatic juice reflux.. About 80% of the glandular stomach was resected, and a 3-cm segment of the transverse colon interposed isoperistaltically between the remnant stomach and duodenum. Epithelial proliferation, aberrant crypt foci (ACF), and tumors in the interposed colon segment were investigated after 4 months of administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) to rats (ENNG-treated rats).. In the interposed colon, crypt lengths increased significantly, and the number of goblet cells per crypt per 1 mm decreased significantly compared to those in the remnant colon, whether ENNG was administered or not. Both crypt lengths and the number of goblet cells in the interposed colon of controls and ENNG-treated rats showed no significant difference. A proliferating cell nuclear antigen (PCNA) labeling index (LI) of the remnant colon was almost 30% in both controls and ENNG-treated rats. In controls, the PCNA LI in the interposed colon at 4, 8, and 12 months after surgery was 30.8, 31.8, and 47.8%. In ENNG-treated rats, the PCNA LI in the nontumorous mucosa of the interposed colon was 44.9, 55.4, and 61.5% at the above postsurgical intervals. ACF and carcinoma were observed only in the interposed colon of ENNG-treated rats. ACF was observed as early as 4 months after surgery, and its incidence increased serially. Both the incidence of carcinogenesis and the number of tumors had increased 8 months after surgery.. We established a rat model of colonic interposition following gastrectomy. The adaptation of interposed colon mucosa was well conducted. A malignant condition, however, was induced in the interposed colon segment serving as a gastric substitute because of both carcinogen predisposition and prolonged exposure to bile and pancreatic juice reflux.

Topics: Adaptation, Physiological; Animals; Bile; Carcinogens; Colon; Colonic Neoplasms; Epithelium; Gastrectomy; Intestinal Mucosa; Male; Methylnitronitrosoguanidine; Pancreatic Juice; Proliferating Cell Nuclear Antigen; Rats; Rats, Wistar; Time Factors

Curcumin (diferuloylmethane), a yellow pigment that is obtained from the rhizomes of Curcuma longa Linn., is a major component of turmeric and is commonly used as a spice and food-coloring agent. The inhibitory effects of feeding commercial grade curcumin (77% curcumin, 17% demethoxycurcumin, and 3% bisdemethoxycurcumin) in AIN 76A diet on carcinogen-induced tumorigenesis in the forestomach, duodenum, and colon of mice were evaluated. Administration p.o. of commercial grade curcumin in the diet inhibited benzo(a)pyrene-induced forestomach tumorigenesis in A/J mice, N-ethyl-N'-nitro-N-nitrosoguanidine-induced duodenal tumorigenesis in C57BL/6 mice, and azoxymethane (AOM)-induced colon tumorigenesis in CF-1 mice. Dietary commercial grade curcumin was given to mice at: (a) 2 weeks before, during, and for 1 week after carcinogen administration (during the initiation period); (b) 1 week after carcinogen treatment until the end of the experiment (during the postinitiation period); or (c) during both the initiation and postinitiation periods. Feeding 0.5-2.0% commercial grade curcumin in the diet decreased the number of benzo(a)pyrene-induced forestomach tumors per mouse by 51-53% when administered during the initiation period and 47-67% when administered during the postinitiation period. Feeding 0.5-2.0% commercial grade curcumin in the diet decreased the number of N-ethyl-N'-nitro-N-nitrosoguanidine-induced duodenal tumors per mouse by 47-77% when administered during the postinitiation period. Administration of 0.5-4.0% commercial grade curcumin in the diet both during the initiation and postinitation periods decreased the number of AOM-induced colon tumors per mouse by 51-62%. Administration of 2% commercial grade curcumin in the diet inhibited the number of AOM-induced colon tumors per mouse by 66% when fed during the initiation period and 25% when fed during the postinitiation period. The ability of commercial grade curcumin to inhibit AOM-induced colon tumorigenesis is comparable to that of pure curcumin (purity greater than 98%). Administration of pure or commercial grade curcumin in the diet to AOM-treated mice resulted in development of colon tumors which were generally smaller in number and size as compared to the control group of AOM-treated mice. These results indicate that not only did curcumin inhibit the number of tumors per mouse and the percentage of mice with tumors but it also reduced tumor size. Histopathological examination of the tumors sho

Topics: Adenocarcinoma; Adenoma; Adenoma, Villous; Animals; Azoxymethane; Benzo(a)pyrene; Carcinogens; Colonic Neoplasms; Curcumin; Duodenal Neoplasms; Female; Male; Methylnitronitrosoguanidine; Mice; Stomach Neoplasms

It may be useful for therapeutic purposes if experimental colonic cancer can be produced in larger animals. Our protocols for experiment to produce colonic cancer in dog were as follows: Two beagle and 12 mongrel dogs were used. Endoscopic examination was done every month or every other month. 1,2-Dimethylhydrazine (DMH) was given subcutaneously in 3 mongrel dogs once a week for 25 months. The protrusion like verruca was observed macroscopically in colonic mucosa in two of them. Histologically it was like lymph follicle hyperplasia in the submucosa. N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) soaked in sponge was inserted daily into the rectum of 2 beagle and 2 mongrel dogs for about 20.4 months. A leiomyoma of the colon was detected histologically in one beagle. N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) soaked in sponge was inserted daily into the rectum of 4 mongrel dogs for about 26.5 months. During follow up study, adenoma of the colon was detected by biopsy in one dog. ENNG suppository (containing 50 mg of ENNG) was administered through the anus in 3 mongrel dogs. Colon cancer was induced in all of three dogs. There were metastases to the liver, lung and lymph nodes in one of them. Colonic cancer was successfully induced in dogs by suppository of ENNG into the rectum. This model seems to be the most useful for producing experimental colonic cancer.

Topics: 1,2-Dimethylhydrazine; Adenoma; Animals; Carcinogens; Colonic Neoplasms; Dimethylhydrazines; Dogs; Female; Lymphatic Metastasis; Male; Methylhydrazines; Methylnitronitrosoguanidine; Suppositories

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

Experimental colonic carcinoma in a dog was induced by anal insertion of an N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) suppository (each cone containing 50 mg of ENNG) for 17 months. The dog was autopsied 20 months after the initiation insertion of the suppository. Grossly, the colonic wall from the anus of the 10-cm oral side of the colon was thickened, and there was an infiltrating tumor with shallow depressions in the rough mucosa. The lymph node around this portion were enlarged, and white spots were found in the liver and redness in the lungs. Histological examination of the colon revealed a variety of pathologic features, e.g., undifferentiated carcinoma, squamous cell carcinoma and malignant melanoma in the region adjacent to the anus. Well and moderately differentiated adenocarcinomas involving the proper muscle layer were found in a region oral to these tumors and were accompanied by marked invasion of the blood vessels and lymphatic permeation. There were metastases to the liver, lungs and lymph nodes which corresponded to the gross findings, and also metastases to renal glomeruli. A well differentiated adenocarcinoma and signet ring cell carcinoma were evident in the gastric mucosa. This experimental model should be useful for studies related to colonic carcinoma in humans.

Topics: Adenocarcinoma; Animals; Carcinogens; Carcinoma; Carcinoma, Squamous Cell; Colon; Colonic Neoplasms; Dogs; Female; Melanoma; Methylnitronitrosoguanidine; Neoplasms, Experimental; Stomach; Stomach Neoplasms; Suppositories