methylnitronitrosoguanidine and Intestinal-Neoplasms

The present survey deals with requirements the experimental-oncological models used in morphogenetic investigations should meet. Data on ways of inducing tumours of various organs the most suited for such investigations are presented. The available at present literature comprises data on different variants of morphogenesis of tumours; in a number of cases malignant neoplasms can develop against the background of an unchanged structure without previous alterations. Because of a contradictory character of the literature reports on morphogenesis of tumours, further investigations into the morphodynamics of the process of cancerogenesis are needed; at present, this may be successfully implemented if adequate models of the majority of tumour diseases in man are available. These studies are of importance for better understanding of pathogenesis or tumour growth and for ascertaining the concept of precancer changes.

Topics: 2-Acetylaminofluorene; 9,10-Dimethyl-1,2-benzanthracene; Aflatoxins; Animals; Azoxymethane; Benzopyrenes; Brain Neoplasms; Carcinogens; Cricetinae; Dimethylhydrazines; Dogs; Esophageal Neoplasms; Ethionine; Ethylnitrosourea; Female; Hematopoietic System; Intestinal Neoplasms; Liver Neoplasms; Lung Neoplasms; Male; Mammary Neoplasms, Experimental; Methylnitronitrosoguanidine; Methylnitrosourea; Mice; Neoplasms, Experimental; Nitrosamines; Nitroso Compounds; Nitrosoguanidines; o-Aminoazotoluene; p-Dimethylaminoazobenzene; Precancerous Conditions; Rats; Skin Neoplasms; Stomach Neoplasms; Urinary Bladder Neoplasms

High temperature- and pressure-treated garlic (HTPG) has been shown to have enhanced antioxidative activity and polyphenol contents. Previously, we reported that HTPG inhibited 1,2-dimethylhydrazine-induced mucin depleted foci (premalignant lesions) and O6-methylguanine DNA adduct formation in the rat colorectum. In the present study, we investigated the modifying effects of HTPG on N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG)- induced pyloric stomach and small intestinal carcinogenesis in mice. Male C57BL/6 mice were given ENNG (100 mg/l) in drinking water for the first 4 weeks, then a basal diet or diet containing 2% or 5% HTPG for 30 weeks. The incidence and multiplicity of pyloric stomach and small intestinal (duodenal and jejunal) tumors in the 2% HTPG group (but not in the 5% HTPG group) were significantly lower than those in the control group. Cell proliferation of normal-appearing duodenal mucosa was assessed by MIB-5 immunohistochemistry and shown to be significantly lower with 2% HTPG (but again not 5% HTPG) than in controls. These results in dicate that HTPG, at 2% in the diet, inhibited ENNG-induced pyloric stomach and small intestinal (especially duodenal) tumorigenesis in mice, associated with suppression of cell proliferation.

Topics: Animals; Carcinogens; Cell Proliferation; Garlic; Hot Temperature; Immunoenzyme Techniques; Intestinal Neoplasms; Intestine, Small; Male; Methylnitronitrosoguanidine; Mice; Mice, Inbred C57BL; Pressure; Stomach Neoplasms

Studies were carried out to ascertain the efficacy of mild whole body hyperthermia (WBH) as a modifier of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) cytotoxicity in mice. Adult Swiss male mice, 6-8 weeks old, weighing about 25 g were exposed to mild WBH (39 degrees C, 1 h) in a precision temperature controlled environmental chamber maintained at 50-60% relative humidity. Twenty-four hours after treatment, animals were administered with different doses of MNNG either by intraperitoneal (i.p.) injections or by feeding through drinking water and were monitored for survival. The studies revealed that the exposure of animals to mild WBH, 24 h prior to MNNG administration results in an increase in survival and recovery in mean body weight compared with those administered with MNNG only. This suggests that prior WBH treatment can effectively reduce the MNNG cytotoxicity in mice.

Topics: Animals; Body Weight; Carcinogens; Cell Survival; Drinking; Hypothermia, Induced; Intestinal Neoplasms; Lung Neoplasms; Methylnitronitrosoguanidine; Mice; Splenomegaly; Time Factors

Topics: 1,2-Dimethylhydrazine; Adenocarcinoma; Adenoma; Animals; Carcinogens; Colorectal Neoplasms; Dietary Fats; Dimethylhydrazines; Fruit; Intestinal Neoplasms; Male; Methylnitronitrosoguanidine; Rats; Rats, Wistar; Vegetables

Oral administration of N-methyl-N'-nitro-N-nitrosoguanidine induced gastrointestinal tumors in 15 out of 19 rats: six adenomas, seven adenocarcinomas, one fibrosarcoma and one malignant schwannoma that was homotransplantable. Both the original and transplantable tumor exhibited characteristic morphological features and immunoreactivity identical to that of a human malignant schwannoma: positive reaction for S-100 protein, neuron specific enolase, glial fibrillary acidic protein, myelin basic protein and vimentin. In addition, alpha-smooth muscle actin was expressed in both tumors. Cultured tumor cells derived from the transplantable tumor at passage 3 produced 18 clones which showed anchorage independent growth in soft agar. From these clones, two cell lines showing characteristic immunoreactivity, designated as RMS-1 and 2, were established. In general, the immunoreactivities of the two cell lines were similar to those of the original tumor; however, the RMS-1 cell line demonstrated positive immunoreaction for neurofilaments and RMS-2 was negative for alpha-smooth muscle actin. Subcutaneous, injection of cultured cells from both cell lines into athymic BALB/c nude mice induced tumors identical to the original tumor. In the present study, transplantable malignant schwannoma was established in the rat and two phenotypes were isolated and established as cell lines.

Topics: Administration, Oral; Animals; Immunohistochemistry; Intestinal Neoplasms; Male; Methylnitronitrosoguanidine; Neoplasm Transplantation; Neurilemmoma; Phenotype; Rats; Rats, Wistar; Tumor Cells, Cultured

Effects of sodium chloride (NaCl) and ethanol on gastric tumor development in rats after treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were studied. MNNG, dissolved in distilled water (5 g/liter), was administered orally once by gastric tube at a dose of 0.25 ml/10 g body weight to 4-week-old ACI rats. After this carcinogen initiation, animals were fed on a diet containing 10% NaCl (Group 2) or normal diet with 10% ethanol in the drinking water (Group 4). MNNG alone (Group 1), NaCl alone (Group 3), ethanol alone (Group 5), and control (Group 6) animals were also maintained. All survivors were killed one year after the MNNG application. Incidences of tumors in the forestomach and glandular stomach were significantly increased in Group 2 as compared to Group 1 (P less than 0.05). The height of the pyloric mucosa was significantly greater in Group 2 than in Groups 4, 5 or 6 (P less than 0.05). In the fundic area, the mucosal height was significantly decreased in Group 4 as compared to Group 6 (P less than 0.05). The present results demonstrate that whereas tumors in the glandular stomach and forestomach are both promoted by NaCl, ethanol is without influence. Furthermore, NaCl, a promoter of glandular stomach tumorigenesis also increases cell proliferation.

Topics: Animals; Body Weight; Carcinogens; Carcinoma, Squamous Cell; Ethanol; Gastric Mucosa; Intestinal Neoplasms; Male; Methylnitronitrosoguanidine; Neoplasm Metastasis; Organ Size; Rats; Rats, Inbred Strains; Sodium Chloride; Stomach Neoplasms

Eighty rats out of 233 developed malignant tumors in the stomach and small intestine by administration of 100 micrograms/ml N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water for 28 weeks. Fifteen lesions (30%) among the 50 small intestinal carcinomas showed ossification in the tumor, while none in the sarcomas (12 lesions) or gastric adenocarcinomas (59 lesions) showed ossification. Multifocal heterotopic bone formation was found within stroma in close approximation to the neoplastic glands. The islands of bone trabeculae were covered by osteoblast-like cells, and abundant fibroblasts in loose stroma gathered around the bony islands which enclosed osteocytes in lacunae. Neither osteoclast nor cartilage was identified. In 5 cases, ossification was extensive, which comprised the major portion of the stroma. In contrast, intraluminal calcification without ossified foci were occasionally seen in the gastric carcinoma. Ossification of the intestinal tumors correlated to the degree of mucin content (p < 0.05, chi square with Yates' correction), degree of neutrophilic infiltration (p < 0.05), and size of the tumor (p < 0.1). (The average size of the ossified tumor was 21.5 +/- 4.0 mm, while that of nonossified tumors was 12.5 +/- 1.9 mm). The degree of tumoral necrosis, desmoplasia or depth of invasion did not seem to be related to the ossification of the tumor. The ossification rate of this experimental model was much higher than in human cases. Various histologic alterations, such as mucin leakage, inflammatory cell infiltration, necrosis and/or fibrosis, which might be caused by continuous stimulation of the strong carcinogen, may play some role in the ossification of experimental tumors.

Topics: Adenocarcinoma; Animals; Intestinal Neoplasms; Intestine, Small; Methylnitronitrosoguanidine; Ossification, Heterotopic; Rats; Rats, Sprague-Dawley; Staining and Labeling; Stomach Neoplasms

The purpose of this study is to elucidate the participation of Paneth cells in experimentally induced adenocarcinoma of the intestine. The rats were fed with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) dissolved in drinking water ad libitum at a concentration of 100 micrograms/ml for 28 weeks. They were sacrificed 12 weeks after the last MNNG administration. A number of tumor cells containing large eosinophilic granules in their supranuclear cytoplasm (Paneth cells) were observed in about 20% of the experimentally induced adenocarcinoma of the small intestine. The granules were stained positively with Lendrum, periodic acid-Schiff, Masson's trichrome, and Mallory's phosphotungstic acid hematoxylin. Ultrastructurally, the granules were round, osmiophilic, and relatively even in size. We compared the morphologic features of the Paneth cell-containing small intestinal adenocarcinomas (Group I) with those without Paneth cells (Group II). Group I was distinguished from Group II by its better differentiation, larger tumor size and lower incidence of calcification. Although Paneth cells are extremely rare in human gastrointestinal carcinomas, twenty percent of MNNG-induced intestinal carcinomas harbor Paneth cells. The neoplastic Paneth cells in experimental carcinomas may differentiate from uncommitted cells in the deeper portion of the crypt.

Topics: Adenocarcinoma; Animals; Cell Transformation, Neoplastic; Intestinal Neoplasms; Methylnitronitrosoguanidine; Rats; Rats, Inbred Strains

Peculiarities of carcinogenic effect of N-methyl-N'-nitro-N-nitrosoguanidine administered through a stomach tube on rats were studied in 30 rats given 1-2 ml MNNG dissolved in distilled water (5 mg/ml) through a gastric tube for 2-3 days. The procedure is repeated every 4-10 days. This intermittent carcinogen administration continued until week 20; the animals were killed on week 25. All effective 26 (100%) rats had multiple papillomas and squamous cell carcinomas of the forestomach, 5 (19.2%) had adenomatous hyperplasias and adenocarcinomas of the glandular stomach, 7 (26.9%) had adenocarcinomas and sarcomas of the small intestine.

Topics: Adenocarcinoma; Animals; Carcinoma, Squamous Cell; Intestinal Neoplasms; Intestine, Small; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Papilloma; Rats; Sarcoma, Experimental; Stomach Neoplasms; Time Factors

Sequential changes of numbers of pepsinogen 1 (Pg 1)-decreased pyloric glands (PDPG) detected by immunohistochemistry and of the incidence of gastric carcinomas were examined in five different strains of rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG;CAS:70-25-7). Male SD (Crj:CD), WKY (WKY/NCrj), Lewis (LEW/Crj), Wistar (Crj:Wistar) and F344 (F344/DuCrj) rats (40 per strain), were given drinking water containing 100 micrograms/ml MNNG for 30 weeks and then normal tap water, and were killed at week 10, 30 and 50 of the experiment. Adenocarcinomas of the glandular stomach were found in nine of 15 SD rats (60%), in eight of 12 WKY rats (67%), in eight of 15 Lewis rats (53%), in three of 13 Wistar rats (23%) and in one of 18 F344 rats (6%) at week 50. These incidences of carcinomas in SD, WKY and Lewis were significantly higher (P less than 0.01) than that in F344 rats. From week 10, the numbers of PDPG in SD, WKY and Lewis rats were significantly greater (P less than 0.01) than that in F344 rats. From week 30, the numbers of PDPG in Wistar rats were also significantly greater (P less than 0.05-0.01) than that of F344. The susceptibility of rats to induction of gastric carcinoma by MNNG correlated with the susceptibility to induction of PDPG by MNNG in each strain, suggesting that induction of PDPG is a preneoplastic change in chemical gastric carcinogenesis.

Topics: Animals; Gastric Mucosa; Hyperplasia; Immunohistochemistry; Intestinal Neoplasms; Male; Methylnitronitrosoguanidine; Pepsinogens; Precancerous Conditions; Pylorus; Rats; Rats, Inbred Strains; Species Specificity; Stomach Neoplasms

N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) dissolved in distilled water (5 g/l) was administered orally once by gastric tube at a dose of 0.25 ml/10 g body weight to 5-day-old or 28-day-old Wistar Furth (W/Fu) or ACI rats. Gastric tumors in the glandular stomach were found in 58% of 5-day-old ACI rats, but none were found in the rest of the groups. Forestomach tumors were found in both strains of rats at both age groups with incidences of 68-100%. Lung tumors were induced in 64% of 5-day-old and 6% of 28-day-old W/Fu rats, but not in ACI rats. Besides the tumors, a high frequency of hepatic cysts was also noted in ACI rats. Intestinal metaplastic foci with alkaline phosphatase activity were found in the group of 5-day-old ACI rats and none in the rest of the groups. The results showed that the incidences and the locations of tumors in rats induced by MNNG are greatly influenced by both strain and age.

Topics: Age Factors; Animals; Intestinal Neoplasms; Liver Neoplasms; Lung Neoplasms; Methylnitronitrosoguanidine; Mitotic Index; Neoplasms, Experimental; Rats; Rats, Inbred ACI; Rats, Inbred WF; Stomach Neoplasms

N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was given to 3 groups of rats with the drinking water for 32 weeks in different doses: 25, 50 and 100 micrograms/ml. After 50 weeks the induced tumours of the stomach and the upper small intestine were investigated. Most tumours were well differentiated adenocarcinomas or adenomatous-hyperplastic lesions with focal adenocarcinoma. After low MNNG-concentration (25 micrograms/ml) only adenomatous hyperplastic lesions with focal adenocarcinoma were found. A tumour development in connection with intestinal metaplasia was detectable exclusively in two rats of the group receiving 50 micrograms MNNG/ml. The frequency of gastric tumours shows a relatively low peak (3.3 tumours/10 animals) after administering a medium MNNG-concentration (50 micrograms/ml) and a little decrease of the frequency after higher MNNG-concentration, as opposed to the approximately linear dose-related increase of the tumour frequency in the upper small intestine. The highest tumour induction rate was found in the upper small intestine after 100 micrograms MNNG/ml (5.6 tumours/10 rats). It can be concluded that the mucosa of the upper small intestine possesses a greater susceptibility to the carcinogenic effect of MNNG than the glandular stomach of the rat.

Topics: Adenocarcinoma; Administration, Oral; Animals; Cell Transformation, Neoplastic; Dose-Response Relationship, Drug; Hyperplasia; Intestinal Neoplasms; Intestine, Small; Male; Methylnitronitrosoguanidine; Neoplasm Invasiveness; Rats; Rats, Inbred Strains; Stomach; Stomach Neoplasms

The study of the influence of long-term injection of whole bile into rat's stomach on N-methyl-N-nitro-N-nitrosoguanidine-induced tumors revealed an increased frequency of stomach malignancies matched by a lower frequency of those in the small intestine as well as slower rates of growth of gastrointestinal tumors.

Topics: Animals; Bile; Intestinal Neoplasms; Intestine, Small; Male; Methylnitronitrosoguanidine; Rats; Stomach Neoplasms; Time Factors

Analbuminemic rats were found to be highly susceptible to induction of gastric tumors by N-methyl-N'-nitro-N-nitrosoguanidine (67-83 micrograms/ml) given to the rats in drinking water for 32 weeks. The rats were sacrificed at experimental week 44. Gastric tumors were found in 12 of 17 analbuminemic rats (70%) and in 8 of 21 normal rats (38%). Intestinal tumors developed in 7 of 17 (41%) analbuminemic rats and in 9 of 21 (42%) normal rats.

Topics: Animals; Intestinal Neoplasms; Male; Methylnitronitrosoguanidine; Rats; Rats, Inbred Strains; Serum Albumin; Stomach Neoplasms

The effects of tetragastrin and histamine on the incidence and histology of tumors induced in the small intestine by N-methyl-N'-nitro-N-nitrosoguanidine [(MNNG) CAS: 70-25-7] were investigated in male W rats. Animals were given MNNG at 150 micrograms/ml in their drinking water for 25 weeks and then 300 micrograms tetragastrin or 4 mg histamine dihydrochloride sc per day in depot form. Administration of tetragastrin or histamine after MNNG treatment resulted in a significant increase in gastric acid secretion and a significant reduction in the incidence of tumors in the duodenum; however, only histamine decreased the incidence of tumors in the jejunum. Histologically, the tumors induced in the small intestine were mostly adenocarcinomas, and their histologic type was not affected by either tetragastrin or histamine.

Topics: Adenocarcinoma; Animals; Drug Antagonism; Duodenum; Gastric Acidity Determination; Gastrins; Histamine; Intestinal Neoplasms; Jejunum; Male; Methylnitronitrosoguanidine; Rats; Stomach Neoplasms; Tetragastrin

On the basis of paradoxical concanavalin A (Con A) staining, the tendency of tumor cells of gastric phenotype to shift to intestinal phenotype and the stability of the latter phenotype in stomach tumors of different sizes were examined quantitatively with an image processor. Phenotypic expression of tumors of the small intestine was also studied. One hundred male Wistar rats were given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at 50 micrograms/ml in their drinking water for 20 weeks (group 1). Twenty male F344 rats were given methylnitrosourea (MNU) at a dose of 50 mg/kg ip twice a week for 2 weeks (group 2). Rats in group 1 were killed in week 50 of the experiment and rats in group 2 were killed in week 25. In group 1, the percentage areas of intestinal-type cells in small, medium and large adenocarcinoma of the stomach were 0.5, 2.7 and 6.6%, the differences between these values being significant (P less than 0.05-0.01). Intestinal phenotypic expression of tumor cells of the stomach is stable and the proportion of intestinal-type cells in adenocarcinomas of the stomach is higher in the larger tumors. Adenomatous hyperplasias and adenocarcinomas of the small intestine in groups 1 and 2 were all composed entirely of cells of the intestinal type. These results suggested that intestinal-type cells in adenocarcinoma of the stomach did not originate from intestinal metaplasias but from gastric-type cells in stomach adenocarcinomas.

Topics: Adenocarcinoma; Animals; Gastric Mucosa; Hyperplasia; Intestinal Neoplasms; Intestines; Male; Metaplasia; Methylnitronitrosoguanidine; Methylnitrosourea; Nitrosourea Compounds; Phenotype; Rats; Rats, Inbred Strains; Stomach Neoplasms

Cyclosporine administration has been associated with the development of lymphomas in human transplant patients as well as animals. Its effect on the genesis of common epithelial carcinomas is unknown. To investigate this N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was administered in drinking water to Wistar rats. Seventy-five young healthy male animals were divided into six groups and received cyclosporine alone, cyclosporine followed by MNNG, MNNG alone, cyclosporine during MNNG administration, MNNG followed by cyclosporine, and no treatment. Cyclosporine seemed to have minimal overall health effects and no cancers were encountered in the group receiving this agent alone. Animals in all carcinogen-treated groups developed gastric and upper intestinal carcinomas by Week 39. No statistically significant differences among carcinogen-treated groups were evident with respect to tumor incidence, histology, or distribution. There appeared to be trends (not statistically significant) toward a greater incidence of small bowel carcinomas in animals receiving cyclosporine plus MNNG as compared to those receiving MNNG alone; greater multiplicity of small intestinal carcinomas in animals receiving cyclosporine after MNNG as compared to all other groups; and greater incidence of small bowel tumors greater than 1 cm3 in animals receiving cyclosporine after MNNG as compared to all other groups. The median total tumor volume in the animals receiving cyclosporine following carcinogen was significantly greater than in any other group. This study does not support a policy of aggressive surveillance for gastrointestinal carcinoma in the human population receiving cyclosporine.

Topics: Animals; Cyclosporins; Drug Synergism; Intestinal Neoplasms; Intestine, Small; Male; Methylnitronitrosoguanidine; Rats; Rats, Inbred Strains; Stomach Neoplasms

The effect of Pseudomonas aeruginosa colonizing in the gut on the development of gastrointestinal tumors was studied in rats treated orally with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The animals were inoculated with or accidentally colonized by P. aeruginosa after MNNG treatment. In 3 serial experiments, P. aeruginosa-positive, MNNG-treated rats consistently showed a significantly higher incidence of gastric tumors than P. aeruginosa-negative, MNNG-treated animals. The total incidence of gastric tumors was 40% (34/86) in the former, and only 11% (7/61) in the latter. The development of tumors in the small intestine was not likely to be influenced by P. aeruginosa colonization. It is concluded that P. aeruginosa in the gut plays a promoting role in gastric tumorigenesis in rats orally administered with MNNG.

Topics: Animals; Intestinal Neoplasms; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Pseudomonas aeruginosa; Rats; Rats, Inbred Strains; Stomach Neoplasms

Genetic control of the induction of gastric tumors by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was studied in susceptible ACI rats, resistant Buffalo rats, and their F1 and F2 offspring. Both sexes of all strains, initially 7 to 9 weeks old, were given MNNG at a concentration of 83 micrograms/ml in their drinking water for 32 weeks and were sacrificed at experimental Week 72. The incidence of gastric adenocarcinoma in ACI rats was 80% in males and 47% in females; in Buffalo rats, the incidence was 18% in males and 0% in females. F1 hybrids showed the same resistance to MNNG as did Buffalo rats; the incidence of gastric adenocarcinoma was 17% in males and 8% in females. These results suggest that resistance to induction of gastric adenocarcinoma by MNNG is a dominant characteristic. The incidence of gastric adenocarcinoma in the F2 generation was 36% in males and 14% in females, which is close to the 3:1 ratio expected from the segregation of a single resistant gene. In ACI and Buffalo strains and their hybrids, males were more susceptible than females to induction of gastric carcinoma by MNNG. Intestinal tumors were observed mainly in the duodenum and jejunum in both strains and their hybrids, and the incidences were as follows: ACI: males, 67% and females 42%; Buffalo: males, 12% and females, 18%; F1: males, 18% and females, 15%; and F2: males, 15% and females, 19%. Thus, there seems to be a common genetic basis for both gastric and intestinal carcinogenesis by MNNG.

Topics: Animals; Disease Susceptibility; Female; Intestinal Neoplasms; Male; Methylnitronitrosoguanidine; Rats; Rats, Inbred BUF; Rats, Inbred Strains; Stomach Neoplasms

This study deals with the effects of gastrin on the incidence of gastric tumors in rats induced by N-methyl-N'-nitro-N-nitrosoguanidine. Inbred Basel-Wistar rats received N-methyl-N'-nitro-N-nitrosoguanidine in drinking water (50 micrograms/ml for 32 weeks) in order to produce gastric carcinoids. A treatment with s.c. injection of pentagastrin (300 micrograms/kg, once daily for 4 weeks) was started at the beginning of N-methyl-N'-nitro-N-nitrosoguanidine treatment simultaneously, on the 4th, 8th, 16th, and 32nd week after start of N-methyl-N'-nitro-N-nitrosoguanidine treatment, respectively. At autopsy, from the 55th to 60th week after start of the experiment, only in the eighth-week group of gastrin-treated rats was the incidence of gastric carcinoid significantly higher than in the gastrin-untreated group of rats receiving N-methyl-N'-nitro-N-nitrosoguanidine alone. The incidence of adenocarcinoma in the glandular stomach also was high only in the fourth-week group of gastrin-treated rats. However, these effects could not be seen in other gastrin-treated or untreated groups of rats. The data suggest that gastrin treatment in the early stage of rat stomach carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine is effective in increasing the development of gastric tumors.

Topics: Adenocarcinoma; Animals; Carcinoid Tumor; Diet; Drug Synergism; Female; Intestinal Neoplasms; Male; Methylnitronitrosoguanidine; Pentagastrin; Rats; Rats, Inbred Strains; Stomach Neoplasms; Time Factors

Tumors of the gastrointestinal tract were induced in white non-inbred rats exposed to MNNG in various doses. Gastric tumors appeared in the dosage of 153 mg, with its 2 and 3.3 times increase no change in the frequency of gastric tumors was noted. The frequency of jejunal tumors was higher with increased MNNG dosage.

Topics: Animals; Dose-Response Relationship, Drug; Gastrointestinal Neoplasms; Intestinal Neoplasms; Intestine, Small; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Rats; Stomach Neoplasms; Time Factors

Studies were made on the effect of mucin on the induction of gastric carcinomas by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), with or without sodium chloride, in male Wistar rats. Seven groups of rats were treated as follows: Group 4 was given continuously 50 mg MNNG/liter solution to drink and 1 ml of saturated sodium chloride once a week and fed on stock diet supplemented with 4% mucin. Group 2 was given 50 mg MNNG/liter solution and fed on stock diet supplemented with 4% mucin. Group 3 received 1 ml of saturated sodium chloride once a week and 50 mg MNNG/liter solution to drink. Group 1 was treated with MNNG only. Group 5 was fed on stock diet supplemented with 4% mucin. Group 6 was given sodium chloride only. Group 7 was untreated. The incidence of gastric cancer in Group 3 was significantly higher than that in Group 4 (P less than 0.05) or in Group 1 (P less than 0.05). The difference in the incidence of gastric cancer in Groups 2 and 4, and of intestinal tumors in Groups 1 to 4 were not statistically significant. No malignant tumors were seen in Groups 5, 6, and 7. Thus mucin reduced the high incidence of gastric cancer induced by MNNG and sodium chloride to the level induced by MNNG alone, but it had no effect on the incidence of intestinal tumors. The effect of mucin in preventing destruction of the gastric mucosal barrier by sodium chloride and so reducing the induction of gastric cancer is discussed.

Topics: Adenocarcinoma; Animals; Body Weight; Carcinoma; Drug Synergism; Gastric Mucosa; Intestinal Neoplasms; Male; Methylnitronitrosoguanidine; Mucins; Neoplasms, Experimental; Nitrosoguanidines; Rats; Sarcoma, Experimental; Sodium Chloride; Stomach Neoplasms

Leiomyosarcomas of the small intestine were found in dogs during experimental induction of gastric carcinoma by oral administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Leiomyosarcomas were found most frequenly in the duodenum and jejunum, and occasionally in the stomach but never in the ileum, colon, or rectum. The leiomyosarcomas developed in all the dogs given 50 mug/ml of MNNG in deionized water to drink but not in dogs fed on porridge food made from standard pellet diet mashed with MNNG at the same concentration in tap water. Intestinal sarcomas developed in 3 months to 5 years after the end of MNNG administration, and frequently metastasized to the liver and/or the peritoneum.

Topics: Administration, Oral; Animals; Dogs; Female; Intestinal Neoplasms; Intestine, Small; Leiomyosarcoma; Male; Methylnitronitrosoguanidine; Neoplasm Metastasis; Nitrosoguanidines; Sarcoma, Experimental; Stomach Neoplasms; Time Factors

The effects were studied of NaCl on the production of gastric carcinomas by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and by 4-nitroquinoline-1-oxide (NQO) in male Wistar rats. Nine groups of rats were treated as follows: Group 1 was given 50 mg MNNG/liter and 6 g NaCl solution/liter to drink and was fed a stock diet supplemented with 10% NaCl. Group 2 received 1 ml saturated NaCl once a week and 50 mg MNNG/liter to drink. Group 3 was treated with MNNG alone. Group 4 was given a solution of 1 mg NQO once a week and fed a stock diet supplemented with 10% NaCl. Group 5 received a solution of 1 mg NQO saturated with NaCl. Group 6 was given NQO alone. Groups 7 and 8 were given NaCl alone. Group 9 was untreated. Adenocarcinomas developed in the glandular stomach in group 2 at a significantly higher incidence than in group 3. Poorly differentiated adenocarcinomas of the glandular stomach were detected in only groups 1 and 2. One poorly differentiated adenocarcinoma metastasized to the lymph nodes. A high incidence of squamous cell carcinomas of the forestomach was found in groups 4 and 5. No malignant tumors were seen in groups 6-9. NaCl given alone had no apparent carcinogenicity in rats but, when administered with MNNG or NQO, it enhanced the carcinogenic effects of MNNG and NQO in the stomach.

Topics: 4-Nitroquinoline-1-oxide; Adenocarcinoma; Animals; Carcinoma, Squamous Cell; Drug Synergism; Gastric Mucosa; Intestinal Neoplasms; Intestine, Small; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Nitroquinolines; Nitrosoguanidines; Papilloma; Rats; Sarcoma; Sodium Chloride; Stomach; Stomach Neoplasms