methylnitronitrosoguanidine and Adenoma

We propose that SF derived from normal-appearing biopsies of ACR gene carriers exist in an initiated state as the result of a dominant mutation. Based on our studies with the ACR cell system, we further suggest that, although an initiated state is essential to cancer development, not all initiated cells necessarily develop into cancerous cells. The genetic makeup of an initiated cell has been established through linkage between abnormal phenotypic markers and pedigree profiles and through cell hybridization, including initial analysis of gene products. We believe that it is consistent with an autosomal dominant trait. In contrast, cells from patients who are homozygous for chromosomal breakage syndromes, including those with xeroderma pigmentosum, represent an experiment of nature which presumably underlies factors associated with cancer promotion in humans. We have demonstrated that ACR cells can be differentially transformed by oncogenic viruses, a carcinogen (MNNG), and gamma-ray irradiation, and that they can proliferate in vitro after exposure to a tumor promoter (TPA. This simple experimental model provides a novel system for the study of tumor promotion in vitro. We further suggest that, through the use of TPA, various stages associated with cancer development in humans, i.e., initiation through promotion and progression, can be identified in vitro. Attempts to apply these results in vivo are currently in progress. The apparent susceptibility of ACR cells to further transformation by oncogenic viruses and chemical and physical agents indicates that genetic information residing within these cells, probably in the form of a relatively limited and specific number of DNA sequences associated with the ACR mutation, renders them more sensitive to these three distinct classes of carcinogens. We submit that, through our tests on SF, and ACR gene carriers within recognized ACR clusters can be diagnosed at present with sufficient certainty to warrant immediate action. In addition, it seems that the time has arrived for a major undertaking to screen for persons who are likely to be at increased risk of cancer, perhaps through walk-in clinics. An underlying assumption in these studies is that predisposition to cancer, in general, is associated with an autosomal dominant trait in obligatory heterozygote gene carriers.

Topics: Actins; Adenoma; Antigens, Neoplasm; Carcinogens; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cholesterol; Cocarcinogenesis; Colonic Neoplasms; Cytoskeleton; Disease Susceptibility; Genes, Dominant; Humans; Kirsten murine sarcoma virus; Methylnitronitrosoguanidine; Mitochondria; Models, Biological; Mutation; Plasminogen Activators; Prognosis; Rectal Neoplasms

The early sequential development of gastric cancer was studied with experimental animals and examined with respect to what conclusions can be drawn for understanding carcinogenesis in man. After limited oral administration of N-methyl-N'nitro-N-nitrosoguanidine to 174 rats carcinomas developed in most cases directly from the otherwise unchanged mucosa through various successive stages of transformation, without passing through a benign-appearing proliferative or neoplastic epithelial lesion. Focal dysplasia grade I was the first recognizable change observed by light microscopy, followed by dysplasia grade II, and subsequently dysplasia grade III. In spite of very similar morphological characteristics, the experimentally induced dysplasias cannot be simply equated in their etiology and biological behavior with the dysplasias of the human stomach. Dysplasias of grade I and II commonly found in man are usually associated with a chronic gastritis; they are located in the upper third of the mucosa and are for the most part reversible. The experimental dysplasias occuring in the proliferative zone of an otherwise undisturbed mucosa must be considered potentially premalignant, as they are irreversible and develop progressively. This finding points out that in man dysplasias grade III within the regenerative zone of non-inflammatory mucosa should be considered particularly as possible precursors of gastric carcinomas.

Topics: Adenoma; Animals; Female; Gastric Mucosa; Hyperplasia; Methylnitronitrosoguanidine; Neoplasms, Experimental; Precancerous Conditions; Rats; Stomach Neoplasms; Time Factors

Aberrant crypt foci (ACF) are microscopic lesions which have been postulated to precede the development of adenomas, precursors of colon cancer. The gastric M1/MUC5AC mucin has also been described as an early marker of colon carcinogenesis in the human and in the rat. To study changes in mucin expression associated with the genesis of tumors, Wistar rats were treated by intrarectal instillations of MNNG, twice a week for 2 weeks, and were sacrificed 10 (n = 20), 14 (n = 20), 22 (n = 20), 30 (n = 10) and 66 (n = 16) weeks after the beginning of the treatment. In the treated rats, the MUC5AC mucin was mainly expressed in ACF compared with the histologically normal mucosae, which showed few isolated MUC5AC-positive normal crypts. During carcinogenesis, the percentage of large ACF [> or =10 aberrant crypts] increased and the number of MUC5AC-positive (NCs) decreased. At Week 30, small tumors were observed arising from large ACF, both types of lesions expressing MUC5AC. At Week 66, large tumors showed remnants of MUC5AC-positive ACF in their adjacent mucosae. This observation suggests that the expression of MUC5AC is associated with the ACF/adenoma sequence and supports the notion of large ACF as precursors of adenomas/adenocarcinomas. Moreover, the expression of MUC5AC in the transitional mucosa adjacent to both rat and human colon tumors suggests that some human tumors could arise from large ACF, and reinforces the concept of the premalignant potential of these lesions.

Topics: Adenocarcinoma; Adenoma; Animals; Antibodies, Monoclonal; Colonic Neoplasms; Disease Progression; Immunohistochemistry; Intestinal Mucosa; Male; Methylnitronitrosoguanidine; Mucin 5AC; Mucins; Precancerous Conditions; Rats; Rats, Wistar; Time Factors

Strain differences in susceptibility regarding stomach carcinogenesis due to N-methyl-N-nitrosourea were examined in males of six strains of mice: BALB/cA (BALB), C57BL/6N (C57BL6), CBA/JN (CBA), C3H/HeN (C3H), DBA/2N (DBA/2), and CD-1 (ICR). The frequency of pepsinogen-altered pyloric glands (PAPGs), putative precancerous lesions, was highest (19.6+/-9.9%) in the BALB and lowest in the ICR (12.3+/-5.7%) mice (P<0.05). Incidences of adenocarcinomas at week 52 were 59.3% (16 of 27) and 18.5% (5 of 27), respectively (P<0.005). Invasion also tended to be deepest in BALB compared with the other strains. Intestinal alkaline phosphatase-positive intestinal type cells were observed heterogeneously in some hyperplasias, adenomas and adenocarcinomas consisting of gastric type cells. Thus, intestinalization appeared to occur at random in both non-neoplastic and monoclonal neoplastic lesions, making it unlikely that IAP-positive cells could be precursors of gastric tumors. In contrast, the data suggest a direct histogenetic role for the PAPG, a useful preneoplastic marker lesion in mouse strains.

Topics: Adenocarcinoma; Adenoma; Alkaline Phosphatase; Animals; Disease Susceptibility; Immunohistochemistry; Intestinal Mucosa; Male; Methylnitronitrosoguanidine; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred DBA; Mice, Inbred ICR; Pepsinogen A; Precancerous Conditions; Pylorus; Species Specificity; Stomach; Stomach Neoplasms; Survival Rate

The aim of this study was to evaluate the early influence of Helicobacter pylori infection on cell kinetics in the antral mucosa of mice exposed to N-methyl-N'-nitro-N'-nitrosoguanidine (MNNG) and bile alone or in combinations. Four hundred and one C57BL/6 male and female mice were assigned into seven treatment groups and one non-treated control group. The gastric antrums were assessed by histology and immunohistochemistry for studies of cell proliferation and apoptosis at 32 and 44 weeks. One female and one male mouse had developed dysplastic adenomas in the pylorus mucosa and one male animal had dysplastic proliferation in the antrum. Only one of these lesions occurred in a H. pylori colonized animal. H. pylori infection significantly increased the cell proliferation at 32 weeks and promoted the cell proliferation in the MNNG and bile group at 44 weeks. Female mice showed less increase in cell proliferation than did the males. No change in apoptosis was seen in any of the groups. Bile had no promotional effect on cell proliferation. These results indicate that H. pylori infection has the potential to alter epithelial cell kinetics as well as antrum mucosa of an animal species that is regarded as resistant to MNNG. However, this change is not sufficient to promote the early development of neoplastic lesions.

Topics: Adenoma; Animals; Apoptosis; Carcinogens; Disease Models, Animal; Epithelium; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Immunohistochemistry; In Situ Nick-End Labeling; Ki-67 Antigen; Kinetics; Male; Methylnitronitrosoguanidine; Mice; Mice, Inbred C57BL; Pyloric Antrum; Stomach Neoplasms; Taurocholic Acid

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

Recently, an epidemiological study showed a lower risk of gastric cancer among people who consume a large amount of green tea. (-)-Epigallocatechin gallate (EGCG), one of the main constituents of green tea, inhibited tumor promotion by teleocidin in a two-stage carcinogenesis experiment with the use of mouse skin. The inhibitory effect of EGCG on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced carcinogenesis of the glandular stomach in rats was examined. The percentage of tumor-bearing rats in the group treated with MNNG plus EGCG was 31%, compared to 62% in the MNNG group. The difference was statistically significant (P < 0.05). To assess the effect of p.o. administration of EGCG, the gastric mucosal cellular kinetics was examined with the use of the bromodeoxyuridine labeling index, ornithine decarboxylase activity, and tissue polyamine levels. The labeling index of the EGCG treatment group decreased significantly (P < 0.05) compared to the EGCG plus MNNG treatment group. The ornithine decarboxylase activity and tissue spermidine levels were also decreased. On the other hand, the tissue putrescine and spermine levels were partly increased. These findings suggest that EGCG inhibits the cellular kinetics of the gastric mucosa during the promotion stage of MNNG-induced gastric carcinogenesis. EGCG may be useful in preventing gastric carcinogenesis. Moreover, EGCG may be applied clinically without any harmful effects and at a low cost.

Topics: Adenocarcinoma; Adenoma; Animals; Antineoplastic Agents; Carcinoma, Papillary; Catechin; Drug Screening Assays, Antitumor; Male; Methylnitronitrosoguanidine; Ornithine Decarboxylase; Papilloma; Rats; Rats, Wistar; Stomach Neoplasms

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

A polyclonal antibody against rat intestinal-type alkaline phosphatase (I-ALP) was generated and proven to be applicable immunohistochemically to paraffin-embedded sections. Expression of I-ALP in normal tissues, intestinal metaplasia and stomach tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was then investigated in five different strains of rats. Male SD (Crj:CD), Lewis (LEW/Crj), WKY (WKY/NCrj), Wistar (Crj:Wistar) and F344 (F344/DuCrj) animals were given drinking water containing 100 micrograms/ml of MNNG for 30 weeks and were killed at week 50. Among the 5 strains, stomach adenocarcinomas were found most frequently in the SD case. The susceptibility of rats to induction of stomach carcinoma did not correlate with the development of intestinal metaplasias in each strain. Histochemical staining for mucin demonstrated all stomach tumors (adenomatous hyperplasias and well-differentiated adenocarcinomas) to consist mainly of gastric type cells (pyloric gland cell and surface mucous cell types), with intestinal-type tumor cells (goblet cell and intestinal absorptive cell types) being only occasional findings. Immunohistochemically, I-ALP was strongly positive on the striated cell borders of small intestinal absorptive cells of the villus and on brush borders of epithelial cells of kidney proximal tubules. I-ALP was also detected in the normal stomach, limited to the striated cell borders of absorptive cells of the upper one-fourth of intestinal metaplastic glands. I-ALP may thus be a useful marker for stomach tumor cells of intestinal absorptive cell type, indicative of maturation and differentiation. No stomach tumors consisting mainly of intestinal-type cells were found, and therefore there was no suggestion of any derivation from intestinal metaplasias.

Topics: Adenocarcinoma; Adenoma; Alkaline Phosphatase; Animals; Immunoenzyme Techniques; Intestines; Male; Metaplasia; Methylnitronitrosoguanidine; Mucins; Rats; Rats, Inbred Strains; Rats, Sprague-Dawley; Rats, Wistar; Stomach Neoplasms

The influence of different doses of sodium chloride (NaCl) on glandular stomach carcinogenesis was examined in male outbred Wistar rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Rats were given 100 p.p.m. MNNG in their drinking water for 8 weeks and then fed a diet supplemented with NaCl at doses of 10, 5, 2.5 or 0% for the next 82 weeks. The administration of 10% and 5% NaCl significantly enhanced the development of gastric adenocarcinomas and adenomas in a dose-dependent manner. Similar but non-significant tendencies for increase were also seen in the group given 2.5% NaCl compared to the MNNG-alone group values. Clear linear correlations between incidences of adenocarcinomas and/or adenomas and the concentration of supplemented NaCl were found. Mesenchymal tumors were also induced in the stomach of rats given MNNG, although the incidence was not statistically different between groups. Independent of the MNNG treatment, urinary lipid peroxidation levels were significantly increased in the NaCl-treated groups as compared to the control values. Thus, the results in the present study indicate that NaCl exerts dose-dependent tumor promoting activity on gastric carcinogenesis in rats, even at doses as low as 2.5%, when given after MNNG initiation.

Topics: Adenocarcinoma; Adenoma; Animals; Cocarcinogenesis; Dose-Response Relationship, Drug; Lipid Peroxidation; Male; Methylnitronitrosoguanidine; Rats; Rats, Wistar; Sodium Chloride; Stomach Neoplasms

Male Wistar rats were treated concurrently with a combination of the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG; CAS 70-25-7) and the polyamine-synthesis inhibitor alpha-difluoromethylornithine (DFMO) at two different doses of 0.5% and 1.0% (w/v). Experimental groups were treated with (I) MNNG alone (n = 25), (II) MNNG plus 0.5% (w/v) DFMO (n = 25), (III) MNNG plus 1.0% (w/v) DFMO (n = 25), (IV) 1.0% (w/v) DFMO alone (n = 25). Group V represented untreated controls (n = 20). Both the carcinogen and DFMO were administered in drinking water. The treatment time with the carcinogen and DFMO was 35 weeks. After treatment was completed animals were followed for an additional 50 weeks to cover a total observation time of 85 weeks. Significantly fewer animals developed gastric adenocarcinoma in the two groups of animals that received a combined treatment of MNNG plus DFMO compared to animals treated with the carcinogen alone (P < 0.05 and 0.005). No benign or malignant neoplastic lesions were observed in the stomach or duodenum of animals treated with DFMO alone or in untreated controls. It is concluded that concurrent treatment with DFMO prevents the development of malignant gastric epithelial tumors induced by MNNG in rats.

Topics: Adenocarcinoma; Adenoma; Animals; Cell Transformation, Neoplastic; Duodenal Neoplasms; Eflornithine; Male; Methylnitronitrosoguanidine; Rats; Rats, Wistar; Sarcoma, Experimental; Stomach Neoplasms

Male Wistar rats were treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) either as a single dose of 50, 125 or 250 mg/kg given by gavage or via drinking water for 28 weeks at a concentration of 40, 80 or 160 micrograms/ml, in the case of the higher concentration reverting to 80 micrograms/ml after the first 8 weeks. The single dose regimen had no effect on water intake or body weight, but the chronic exposure led to a dose-dependent reduction in water intake that was paralleled by a slower weight gain, with the final body weights at approximately 90, 84 and 79% of the control weight values. The combined yield of benign and malignant tumours (79-100% of the animals treated) occurred in the forestomach in the case of the single doses, whereas the chronic exposure resulted in a maximum yield of tumours located in the pyloric region of the glandular stomach (64-100% of animals treated). The principal histological types of tumours induced were squamous cell papilloma and carcinoma in the forestomach and adenocarcinoma in the pylorus. There was a persistent, but low yield (25-30% of animals treated) of tumours in the jejunum, mainly adenocarcinoma, after administration via drinking water, whereas after single doses, multiple solitary cysts and cholangioma (30% and 25-70% respectively of the animals treated) were found in the liver. This report differs from earlier reports in that marked effects were noted on water consumption and body weight gain and that tumour induction can be achieved after much shorter periods of exposure than previously reported in the literature. These data confirm the tissue specificity of MNNG when given either as a single or chronic dose regimen and provide a suitable model for the investigation of the target cell specificity of tumour induction.

Topics: Adenocarcinoma; Adenoma; Administration, Oral; Animals; Body Weight; Dose-Response Relationship, Drug; Drinking; Drug Administration Schedule; Duodenal Neoplasms; Gastrointestinal Neoplasms; Jejunal Neoplasms; Liver Neoplasms, Experimental; Male; Methylnitronitrosoguanidine; Pylorus; Rats; Rats, Wistar; Stomach Neoplasms

Three hundred and ninety LACA mice of seven weeks old were used in 2 batches (96.4 wks and 106 wks) for studying the preventive effect of green tea on MNNG-induced lung cancers and precancerous lesions. These mice (within each batch) were randomly allocated to four groups, namely, positive control (MNNG), green tea (GT), complex (MNNG + GT), and blank control (C) group. In MNNG group, MNNG 250 micrograms) was injected intravenously every five days for seven times in each mouse; the total dosage of MNNG was 1.75mg. In GT group, according to W/W, 5% GT dust was well mixed into 95% common diet for long-term breeding. In complex group, MNNG was given as that in MNNG group and the mice were reared as those in GT group. The mice in MNNG group and in C group were all reared by common diet. The mean amount of daily intake of feed was 10g. The number of effective animals was 354. The results of experiments showed different degrees of preventive effect of green tea on MNNG-induced lung cancers and precancerous lesions in LACA mice. Green tea exerted an effect on the number of induced cancers and precancerous lesions, causing a drop of the cancerous rate from 79.75% to 13.59% and the number of lung tumor down to 1/7-1/16 that of the MNNG group, i.e. down to less than one tumor nodule per mouse.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenoma; Animals; Lung Neoplasms; Methylnitronitrosoguanidine; Mice; Plant Extracts; Precancerous Conditions; Tea

550 seven-wk-old LACA mice were used in 3 batches for studying the inhibitory effect of refined Amorphophallus konjac (Konjaku powder) on MNNG-induced lung cancers. The mice (within each batch) were randomly allocated into four groups, namely, positive control (MNNG), Amorphophallus konjac (A. K.), complex (MNNG+A. K.), and blank control (C) groups. In MNNG group, MNNG (250 micrograms) was injected intravenously once every five days for seven times in each mouse, the total dosage of MNNG being 1.75 mg. In A. K. group, according to w/w, 8% A. K. was well mixed into 92% common diet for long-term breeding. In the complex group, MNNG was given as that in MNNG group and the mice were kept as those in A. K. group. The mice in MNNG group and in C group were all maintained on common diet. The results showed different degrees of inhibitory and preventive effect of refined A. K. on MNNG-induced lung cancers. Refined A. K. not only exerted effect on the number of induced cancer and precancerous lesions, causing a drop in cancer rate from 70.87% to 19.38% and the mean number of cancer and precancerous lesions in each animal, but also altered the constituent ratio of the kinds of tumors, showing a decrease in malignancy (adenoma with malignant change), absence of adenocarcinoma, and relative increase in benign adenoma. The results of experiments in 3 batches also exhibited good reproducibility as well as absence of adverse reaction to Konjaku powder.

Topics: Adenocarcinoma; Adenoma; Animals; Dietary Fiber; Female; Lung Neoplasms; Male; Mannans; Methylnitronitrosoguanidine; Mice; Precancerous Conditions

Topics: Adenoma; Animals; Antioxidants; Butylated Hydroxyanisole; Carcinoma; Cell Division; Epithelium; Female; Hyperplasia; Lipid Peroxidation; Male; Methylnitronitrosoguanidine; Papilloma; Rats; Rats, Inbred F344; Stomach; Stomach Neoplasms

Histochemical markers are important for the early detection of chemically initiated neoplasia in experimental animal studies. The marker, iron resistance, was evaluated in the Shasta strain of rainbow trout (Salmo gairdneri). Twenty-one-day-old trout embryos were exposed to 100 ppm aqueous N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 30 min in a static water bath. Fish were fed a semipurified diet, and sampled monthly from the 4th to the 9th month. Two days before sampling, fish were iron-loaded with a single ip dose of 0.30 mg iron dextran/100 g body weight. Livers and kidneys were conventionally processed to paraffin sections for iron, or hematoxylin and eosin (H&E) staining. Normal hepatocytes accumulated iron in pericanalicular locations, but in hepatocytes from carcinogen-altered foci and tumors, iron staining was clearly reduced or absent. Normal renal tubule cells exhibited slight to moderate iron staining, while those from nephroblastoma were iron resistant. These results establish iron resistance as a property of preneoplastic and neoplastic trout hepatocytes and nephroblastoma cells for the first time. Iron resistance may offer a practical histochemical marker in experimental fish models of hepatocellular carcinoma and nephroblastoma.

Topics: Adenoma; Animals; Biomarkers, Tumor; Chemical and Drug Induced Liver Injury; Histocytochemistry; Iron; Kidney Neoplasms; Liver Neoplasms, Experimental; Methylnitronitrosoguanidine; Salmonidae; Trout; Wilms Tumor

Modifying effects of resorcinol, hydroquinone, p-tert-butylcatechol (PTBC), p-methylcatechol (PMC), and o-methylcatechol on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced forestomach and glandular stomach carcinogenesis were investigated in F344 rats. Groups of 15 to 16 male 6-wk-old animals were given a single intragastric administration of 150 mg/kg of body weight of MNNG and starting 1 wk later were administered powdered diet containing 0.8% resorcinol, 0.8% hydroquinone, 1.5% PTBC, 1.5% o-methylcatechol, 1.5% PMC, or basal diet alone for 51 wk. Additional groups of 10 to 15 rats each were treated with the phenolic compounds or received basal diet without prior carcinogen exposure. Histological examination after sacrifice at Wk 52 revealed that squamous cell carcinoma development in the forestomachs of rats treated with MNNG followed by PTBC (75%, P less than 0.001) or MNNG followed by PMC (100%, P less than 0.001) was significantly greater than in animals receiving MNNG alone (20%). Treatment with PMC alone also resulted in a 40% yield of papilloma. In the glandular stomach, incidences of adenomatous hyperplasias in rats treated with MNNG followed by PTBC (31.3%, P less than 0.05) or PMC (100%, P less than 0.001) and the incidence of adenocarcinomas in rats treated with MNNG followed by PMC (100%, P less than 0.001) were significantly higher than in controls. In addition, PMC alone induced a 100% yield of adenomatous hyperplasias and 6.7% of adenocarcinomas. Thus, the results demonstrated that PTBC and PMC treatment significantly enhances forestomach and glandular stomach carcinogenesis and that PMC itself may possess weak carcinogenic potential in these organs. The ortho-position appears to be important for this dihydroxybenzene activity.

Topics: Adenocarcinoma; Adenoma; Animals; Hyperplasia; Male; Methylnitronitrosoguanidine; Phenols; Rats; Rats, Inbred F344; Stomach; Stomach Neoplasms; Structure-Activity Relationship

The comparative sensibility of the stomach gland epithelium and the epithelium of experimental gastric adenomatous diverticuli to carcinogenic action of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was examined in experiments carried out in 107 rats; pathohistological techniques and electron-microscopic methods were applied. The epithelium of adenomatous diverticuli showed no signs of atypia or neoplasia in the course of MNNG-induced gastrocarcinogenesis. On the contrary, the epithelium of the gland cambial zone developed precancerous changes and adenocarcinomas. The formation of experimental diverticuli did not stimulate the development of rat stomach cancer.

Topics: Adenoma; Animals; Diverticulitis; Diverticulum, Stomach; Female; Foreign Bodies; Gastric Mucosa; Methylnitronitrosoguanidine; Rats; Stomach Neoplasms

Reflux of duodenal contents into the stomach occurs in patients with pyloric incompetence and after gastric resection when bile-diverting procedures are omitted. In such settings duodenal contents have been considered to favor the development of gastric cancer. We have studied the effect of chronic duodenogastric reflux on gastric tumor promotion in rats treated with N-methyl-N'-nitrosoguanidine (MNNG) in an experimental design that avoids physical trauma to the glandular stomach. Thus the effect of trauma-induced tissue repair on carcinogenesis is eliminated, and duodenogastric reflux is isolated as an experimental parameter. To achieve such reflux the first jejunal loop was anastomosed to the forestomach in rats. Animals were exposed to MNNG in drinking water (83 mg/L) for 12 weeks before induction of reflux. Experimental groups were as follow: I, reflux plus MNNG (n = 32); II, MNNG alone (n = 27); III, reflux alone (n = 28); IV, control (n = 25). The experiment was terminated after 56 weeks. Only animals that had survived for 90 days were included in the effective number of animals, which allowed for equal chances of tumor development. In no animal that died earlier had tumors developed. Animals with reflux plus MNNG treatment had significantly more glandular neoplasms (12/32) than did animals with MNNG treatment alone (4/27; p less than 0.05). Similarly, more animals with squamous cell neoplasms were recorded in group I (9/32) than in group II (2/27; p less than 0.05). In consideration of all tumors of epithelial and mesenchymal origin, more gastric malignant tumors were observed in group I (9/32) than in group II (2/27; p less than 0.05). It is concluded that chronic exposure to duodenal contents promotes the development of gastric neoplasia.

Topics: Adenocarcinoma; Adenoma; Animals; Carcinoma, Squamous Cell; Cocarcinogenesis; Duodenogastric Reflux; Male; Methylnitronitrosoguanidine; Rats; Rats, Inbred Strains; Stomach Neoplasms

Catechol (CAS: 120-80-9) is present in the environment, being a major industrial chemical as well as a major phenolic component of cigarette smoke. Continuous oral treatment of rats with 0.8% catechol for 51 weeks after a single intragastric dose of 150 mg/kg of N-methyl-N'-nitro-N-nitrosoguanidine strongly enhanced both forestomach and glandular stomach carcinogenesis. In addition, and more importantly, catechol alone induced adenocarcinoma and adenomatous hyperplasia in the pyloric region of the glandular stomach. These results clearly indicate that this environmental contaminant merits classification as an enhancer of forestomach and glandular stomach carcinogenesis with complete carcinogenic potential for the glandular stomach. Its significance for gastric tumor development in man requires elucidation.

Topics: Adenocarcinoma; Adenoma; Animals; Carcinogens, Environmental; Catechols; Cocarcinogenesis; Male; Methylnitronitrosoguanidine; Rats; Rats, Inbred F344; Stomach Neoplasms

The influence of dietary selenium on the incidence of stomach carcinoma induced by N-methyl-N'-nitro-N-nitrosoguanidine was studied in 108 rats that survived for over 10 wk. The incidence of glandular stomach cancer in the high-selenium (4.0 ppm) diet group (20 carcinomas in 54 rats) was lower than in the low-selenium (0.1 ppm) diet group (33 carcinomas in 54 rats). The selenium level and glutathione peroxidase activity in the blood, liver, and stomach mucosa were significantly higher in the high-selenium diet group than in the low-selenium diet group. Glutathione peroxidase activity as well as the concentration of selenium in the glandular stomach was increased significantly in the high-selenium diet group.

Topics: Adenocarcinoma; Adenoma; Animals; Body Weight; Carcinoma; Diet; Gastric Mucosa; Glutathione Peroxidase; Liver; Methylnitronitrosoguanidine; Rats; Sarcoma, Experimental; Selenium; Stomach Neoplasms

The effect of sodium chloride on the promotion stage of gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was studied in male inbred Wistar rats. Rats in group I were given MNNG at a concentration of 50 micrograms/ml in their drinking water for 12 weeks and then 1 ml of saturated NaCl solution intragastrically once a week until experimental week 65. Rats in group II were given MNNG for 12 weeks and then 1 ml of distilled water intragastrically once a week until week 65. Rats in group III were not treated for the first 12 weeks and were then given 1 ml of saturated NaCl solution intragastrically once a week until week 65. The incidence of adenomatous hyperplasias in the glandular stomach was significantly higher in group I than in group II, but the incidences of gastric adenocarcinomas and adenomas in groups I and II were not significantly different. No neoplastic or preneoplastic changes were observed in the stomach in group III.

Topics: Adenocarcinoma; Adenoma; Animals; Carcinogens; Cocarcinogenesis; Male; Methylnitronitrosoguanidine; Rats; Rats, Inbred Strains; Sodium Chloride; Stomach Neoplasms

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adenocarcinoma, Papillary; Adenoma; Animals; Dogs; Male; Methylnitronitrosoguanidine; Stomach Neoplasms

No relationship was found between general sensitivity of rats to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as identified by tumor incidence and mean latent period of tumorigenesis and the age of experimental animals at the beginning of treatment.

Topics: Adenocarcinoma; Adenoma; Age Factors; Animals; Ileal Neoplasms; Male; Methylnitronitrosoguanidine; Rats; 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

Topics: Adenocarcinoma; Adenoma; Animals; Diet; Female; Jejunal Neoplasms; Male; Methylnitronitrosoguanidine; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Rats; Rats, Inbred Strains; Sodium Chloride; Stomach Neoplasms

The effect of tetragastrin on the incidence and histology of colonic tumors induced by intrarectal instillation of N-methyl-N'-nitro-N-nitrosoguanidine was investigated in Wistar rats. Prolonged administration of tetragastrin in depot form during and after treatment with N-methyl-N'-nitro-N-nitrosoguanidine resulted in a significant reduction in the incidence of colonic tumors in Experimental Week 35. Histological examinations showed that, unlike the well-differentiated adenocarcinomas with a typical glandular pattern in control groups, the adenocarcinomas that developed in rats treated with tetragastrin had high mucin-producing activity.

Topics: Adenocarcinoma; Adenoma; Animals; Colonic Neoplasms; Gastrins; Injections, Subcutaneous; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Rats; Rats, Inbred Strains; Sarcoma; Tetragastrin

Rats reveal distinct variations in response to carcinogenic action. The highest frequency of stomach tumors (69.6%) and the shortest period of their development (54.7 weeks) were registered in noninbred rats. Multiple lesions of the gastrointestinal tract were relatively frequent, too. Augustus and Penguin rats responded with a high frequency of tumor development. However, tumors arose in them later than in noninbred rats. Wistar rats appeared to be relatively resistant to MNNG action.

Topics: Adenocarcinoma; Adenoma; Animals; Carcinoma, Squamous Cell; Gastrointestinal Neoplasms; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Rats; Rats, Inbred Strains; Sarcoma, Experimental

Skin fibroblasts from patients with familial adenomatosis coli (AC) and normal individuals were treated once with the carcinogen 4-nitroquinoline 1-oxide or N-methyl-N'-nitro-N-nitrosoguanidine and then passaged sequentially. Morphologically altered cells appeared in the cultures of carcinogen-treated AC fibroblasts at passages 6-8 (days 100-140) after treatment with the carcinogens, but carcinogen-treated normal cells and untreated AC and normal cells did not become altered even after cultivation for 25 passages. The cultures containing morphologically altered cells showed characteristics of transformed cells, such as a high frequency of colony formation in soft agarose, increased growth ability, and chromosomal abnormalities. The results suggest tha AC patients have increased susceptibility to morphologic transformation and chromosomal changes induced by chemical carcinogens.

Topics: 4-Nitroquinoline-1-oxide; Adenoma; Cell Count; Cell Division; Cell Transformation, Neoplastic; Cells, Cultured; Chromosome Aberrations; Colonic Neoplasms; Female; Humans; Methylnitronitrosoguanidine; Middle Aged; Skin

Gastric tumours were induced in rats by orally administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The received adenomas and adenocarcinomas were investigated electron microscopically. In this paper we give a short description of main ultrastructural specialities of tumour cells, which can be derived from mucoid surface cells and mucous cells of antropyloric glands.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adenoma; Animals; Methylnitronitrosoguanidine; Microscopy, Electron; Neoplasms, Experimental; Rats; Stomach; Stomach Neoplasms

We have studied the chromosomal sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) of human diploid skin fibroblasts derived from individuals with adenomatosis coli (AC), which is a dominantly inherited disorder associated with multiple adenomas of the colon and rectum. Spontaneous frequencies of chromosome aberrations in the cell strains from the AC patients were similar to those in the control cells from normal individuals. However, the AC cells exhibited elevated chromosome instabilities when cells were expected to MNNG, with aberration frequencies approximately twice as high as in similarly treated control cells. The present results, together with findings by others, suggest that the AC cells are defective in a function which regulates cellular condition and are in a state more susceptible to the action of agents that react with chromosomal DNA. These findings also raise the possibility of developing a diagnostic procedure for early detection of abnormal gene carriers of AC.

Topics: Adenoma; Adult; Cell Cycle; Cells, Cultured; Child; Chromosome Aberrations; Chromosomes, Human; Colonic Neoplasms; Dose-Response Relationship, Drug; Female; Fibroblasts; Humans; Male; Methylnitronitrosoguanidine; Middle Aged; Rectal Neoplasms; Skin

Malignant transformation of rat stomach was studied after oral administration of MNNG. The lesions were investigated with cytomorphological and histochemical methods, while the alkaline phosphatase (ALP) isoenzyme pattern was investigated by means of gel electrophoresis. Hyperdiploid-aneuploid DNA values were observed in dysplasias, as well as in carcinomas. The liver type ALP isoenzyme could be detected in intact and regenerative gastric mucosa. It also occurred in atypical hyperplasia and carcinoma. Placental type ALP isoenzyme was absent in all intact or regenerating gastric mucosa, but present in atypical hyperplasias and carcinomas. It can be concluded that DNA aneuploidy and the presence of placental type ALP are indicative of malignant transformations. The MNNG-induced adenomatous hyperplasia associated with atypia behaved like cancer and can thus be regarded as an obligatory preneoplastic lesion.

Topics: Adenoma; Animals; Carcinoma; Hyperplasia; Methylnitronitrosoguanidine; Precancerous Conditions; Rats; Stomach; Stomach Neoplasms; Time Factors

Chemical transformation of cultured human skin fibroblasts (PF) derived from individuals with hereditary adenomatosis of the colon and rectum is reported. Cells treated only with various levels of N-methyl-N'-nitro N-nitrosoguanidine (MNNG) underwent morphological alteration. The morphologically altered cells formed large aggregates when suspended in liquid growth medium above an agar base and grew to high saturation densities. One altered (MNNG, 1.0 microgram/ml) cell culture formed colonies in soft agar. Transformed cells were resistant to rechallenge of MNNG (l microgram/ml) and showed a more prolonged life-span compared to the untreated cells. Altered cells became heteroploid cells. However, no progressively growing tumors were produced when cells were inoculated subcutaneously into nude mice. The data suggest that chemical carcinogens alone may not induce neoplastic transformation of fibroblasts from humans genetically predisposed to cancer and that neoplastic transformation of these skin cells by chemical carcinogens might require the presence of a tumor promotor and the use of an immuno-privileged site in the nude mouse system.

Topics: Adenoma; Cell Transformation, Neoplastic; Colonic Neoplasms; Fibroblasts; Humans; Methylnitronitrosoguanidine; Rectal Neoplasms; Skin

Topics: Adenocarcinoma; Adenoma; Animals; Cholesterol; Cocarcinogenesis; Colonic Neoplasms; Female; Germ-Free Life; Lithocholic Acid; Methylnitronitrosoguanidine; Neoplasms, Experimental; Rats; Rats, Inbred F344

The promoting effect of croton oil on gastrocarcinogenesis by MNNG was examined in male Wistar rats. Gastric carcinomas were found in five of 10 rats given 83 micrograms/ml MNNG for three months and then 0.02% croton oil with 0.5% Tween 60 as solvent for nine months. No gastric carcinomas were found in rats given MNNG for three months and then Tween 60 only for nine months. The incidence of gastric carcinomas in these two groups was significantly different (p less than 0.05). No tumors were found in rats given only croton oil with Tween 60.

Topics: Adenocarcinoma; Adenoma; Animals; Croton Oil; Dose-Response Relationship, Drug; Drug Synergism; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Polysorbates; Rats; Stomach Neoplasms

Differences in susceptibility to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) of fundic mucosa in various states of regeneration after induction of ulcer with iodoacetamide were examined histologically in male Wistar rats. Iodoacetamide was given to rats in their drinking water, before (Group 1), with (Group 2), or after (Group 3) MNNG. Atypical hyperplasia in the renewed mucosa and pyloric gland metaplasia were observed on the ulcers in Group 1 in higher incidence than in Groups 2 and 3. In addition, adenocarcinoma developed in the ulcer of 2 of 17 effective animals in Group 1. These observations suggest that the mucosa showing pyloric gland metaplasia is more susceptible to MNNG than the young rapidly regenerating mucosa at the margin of ulcers.

Topics: Adenocarcinoma; Adenoma; Animals; Gastric Mucosa; Hyperplasia; Iodoacetamide; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Precancerous Conditions; Rats; Regeneration; Stomach Neoplasms; Stomach Ulcer

Experimentally induced tumours in the colon of the rats were examined with a double contrast method. Carcinogenic agents were administered to 114 rats. The development of the colonic tumors was recorded by repeated examinations. In the dead rats a thorough necropsy was performed. The radiographic and microscopic results were correlated and the radiographic appearances of colonic tumours were evaluated. The diagnostic accuracy of the radiographic method in distinguishing between benign and malignant lesions was 92 per cent.

Topics: Adenocarcinoma; Adenoma; Animals; Colon; Colonic Neoplasms; Contrast Media; Dimethylhydrazines; Female; Intestinal Mucosa; Intestinal Polyps; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Radiography; Rats

In 189 rats N-methyl-N'-nitro-N-nitrosoguanidine or 1,2-dimethylhydrazine (DMH) was given in order to induce colonic tumours. The tumour induction was followed by double contrast examination. At 894 examinations 196 adenomatous tumours were revealed. Autopsy and microscopy revealed 214 macroscopic and 53 microscopic benign or malignant adenomatous tumours. Metastases were found in 17 per cent in the DMH group. The relationship between adenomas and carcinomas is also evaluated.

Topics: Adenocarcinoma; Adenoma; Animals; Carcinogens; Colon; Colonic Neoplasms; Dimethylhydrazines; Female; Hyperplasia; Injections; Injections, Intravenous; Injections, Subcutaneous; Intestinal Mucosa; Male; Methylnitronitrosoguanidine; Neoplasm Metastasis; Neoplasms, Experimental; Radiography; Rats; Rectum; Time Factors

Adenomatous changes, and early and invasive carcinomas of the glandular stomach in Wistar rats ingesting N-methyl-N'-nitro-N-nitrosoguanidine were studied. Almost all adenomatous changes and carcinomata were located near the midpoint of the lesser curvature. In electron microscopic and histochemical studies, both changes showed great cytological similarity. Electron microscopically, they were found to consist of predominantly undifferentiated cells with poorly developed cytoplasmic organelles, with some highly differentiated cells present. Histochemically, both showed strongly positive reactions for lysosomal enzymes. For tumor transplantation, five lesions were used and in all cases, the transplants were successful.

Topics: Adenocarcinoma; Adenoma; Animals; Cell Differentiation; Histocytochemistry; Lysosomes; Male; Methylnitronitrosoguanidine; Microscopy, Electron; Neoplasm Transplantation; Neoplasms, Experimental; Precancerous Conditions; Rats; Rats, Inbred Strains; Stomach Neoplasms; Time Factors; Transplantation, Isogeneic

This study was undertaken to determine the effect of ulcer induced by iodoacetamide on the development of gastric carcinoma by N-methyl-N'-nitro-N-nitrosoguanidine in male Wistar rats. Fifty-six of the 62 ulcers induced by IAM were located in the fundic gland area along the limiting ridge. The incidence of fundic carcinoma was 16% in the groups treated with IAM and MNNG, while no fundic carcinoma was found in the group treated with MNNG alone. This difference was statistically significant. All the carcinomas in the fundic gland area were confined within the ulcer itself or its scar tissue, produced by IAM. These findings indicate that if an ulcer is present, carcinoma develops even in the fundic mucosa which is, if intact, resistant to the carcinogenic stimulation of MNNG. It was concluded that gastric ulcer predisposes the development of gastric carcinoma.

Topics: Adenocarcinoma; Adenoma; Animals; Cell Transformation, Neoplastic; Drug Synergism; Iodoacetamide; Iodoacetates; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Rats; Stomach; Stomach Neoplasms; Stomach Ulcer

Topics: Adenocarcinoma; Adenoma; Animals; Isoenzymes; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Pepsinogens; Precancerous Conditions; Pylorus; Rats; Stomach Neoplasms

Topics: Adenocarcinoma; Adenoma; Animals; Chenodeoxycholic Acid; Cholic Acids; Colonic Neoplasms; Drug Synergism; Female; Germ-Free Life; Methylnitronitrosoguanidine; Neoplasms, Experimental; Rats; Rats, Inbred F344

In rats with Nitrosoguanidine induced carcinomas of the gastric stump, heterotopic ossifications are found freqently. The following stages of differentiation during the desmal ossification in the stump carcinomas are demonstrated: 1. Osteoblasts, 2. Osteoid, 3. Woven bone, 4. Lamellar bone. --The islands of metaplastic bone cells are predominantly located in the invasive marginal zone of the carcinoma of the gastric stump. The histology of the heterotopic ossification in the gastric stump of the rat is similar to that one seen in stomach cancer of men. The model here described seems to be suitable for further study of metaplastic bone formation in the gastrointestinal tract.

Topics: Adenoma; Animals; Carcinoma; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Ossification, Heterotopic; Osteogenesis; Precancerous Conditions; Rats; Stomach Neoplasms

The effect of ulcers induced by iodoacetamine on the development of gastric tumors by N-methyl-N'-nitro-N-nitrosoguanidine was studied in male Wistar rats. The ulcerative lesions induced by iodoacetamide were confined symmetrically to the fundic region along the limiting ridge in the stomach and the pyloric region was unaffected. Animals treated with iodoacetamide and N-methyl-N'-nitro-N-nitrosoguanidine produced a high incidence of tumors including adenocarcinoma in the fundic region. The incidence of tumors in the pyloric region in the control group was 80% but there were no tumors in the fundic region. The tumors in the fundic region were most frequently found in the same areas that ulcers had previously been induced. These findings suggest that ulceration and regeneration of the mucosa are important factors in gastric carcinogenesis induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine.

Topics: Adenocarcinoma; Adenoma; Animals; Gastric Mucosa; Iodoacetamide; Iodoacetates; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Nitrosoguanidines; Pylorus; Rats; Sarcoma; Stomach Neoplasms; Stomach Ulcer

Female germfree and conventional rats of 50 days of age were injected intrarectally with MNNG for 20 wk (total dose, 48 mg/rat) and autopsied 30 wk after last injection. The colon adenomas induced by MNNG were doubled in germfree rats compared to conventional animals. However, germfree status had no effect on the incidence of adenocarcinomas. It is concluded that pharmacodynamics and metabolism of carcinogen play a role greater than the immune status of the animal in the action of carcinogens such as MNNG.

Topics: Adenocarcinoma; Adenoma; Animals; Colonic Neoplasms; Female; Germ-Free Life; Injections; Methylnitronitrosoguanidine; Neoplasms, Experimental; Nitrosoguanidines; Rats; Rectum

A method to make a diverted segment of the colon keeping direct continuity to the main colonic lumen was introduced to study carcinogenesis in the colon of rats. This method was proved to be useful for analyzing several factors influencing upon cancerization in the colonic mucous membrane. Macroscopical colonic neoplasia were induced in nearly 80% of rats treated with N-methyl-N'-nitro-N-nitrosoguanidine introduced into the colonic lumen through the diverted segment. Neoplastic lesion of the mucous membrane developed mainly in the colonic segments which were in direct contact with intestinal content. The importance of intestinal content and colonic microflora was discussed and reviewed. One epithelial cell line was established from one intraperitoneal metastatic deposit of a huge colonic carcinoma induced by the carcinogen. This cell line has been maintained in tissue culture. The liver was susceptible to the carcinogen, and multiple cystic lesions were observed after intracolonic administration of the chemical.

Topics: Adenoma; Animals; Chemical and Drug Induced Liver Injury; Colon; Colonic Neoplasms; Cysts; Female; Liver; Liver Diseases; Male; Methylnitronitrosoguanidine; Mitosis; Neoplasm Metastasis; Neoplasms, Experimental; Rats