Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The modifying effects of caffeine ingestion on glandular stomach carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride (NaCl) were investigated in male Wistar rats. Animals were given a MNNG solution (100 ppm) as their drinking water and simultaneously fed a diet supplemented with 5% NaCl for 8 wk. They then received 0.25% caffeine solution (groups 1 and 3) or tap water (groups 2 and 4) as the drinking water, and were fed the NaCl diet (groups 1 and 2) or basal diet (groups 3 and 4) for the following 32 wk. Both caffeine and NaCl treatments exerted growth retardation effects, the suppression being stronger with caffeine than NaCl, and animals in group 1 (NaCl plus caffeine) showing the lowest body weight. The incidence of adenocarcinomas in the pylorus was significantly decreased in group 1 compared with the group 2 (NaCl) value (P < 0.05). The incidence of atypical hyperplasias in the fundus was also lower in group 1 than in group 2, although in both cases significantly higher (P < 0.05 and P < 0.01) than in group 4 (no treatment). These results were in good agreement with short-term assay findings whereby lipid peroxidation in the glandular stomach mucosa induced by 4% NaCl ingestion was inhibited by caffeine treatment. In group 3 (caffeine), caffeine intake by itself did not modulate glandular stomach tumour development. The results thus suggest that caffeine inhibits the gastric tumour promotion activity of NaCl in rats.
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PMID:Effects of caffeine on glandular stomach carcinogenesis induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride. 782 72

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.
Carcinogenesis 1994 Jul
PMID:Dose-dependent promoting effects of sodium chloride (NaCl) on rat glandular stomach carcinogenesis initiated with N-methyl-N'-nitro-N-nitrosoguanidine. 803 21

Induction of cell proliferation by laxatives and related compounds in rat intestines was analysed by BrdU-labelling and compared with histopathological changes in the mucosa and findings for feces. Male F344 rats were fed a diet containing danthron, sennosid A, bisacodyl, 1-hydroxyanthraquinone (1-HAQ), magnesium sulfate (MgSO4), dextran sulfate sodium (DSS), pectin, carboxymethylcellulose sodium (CMC-Na) or sodium chloride (NaCl) for 7 days. The stimulant laxatives, danthron, sennosid A and bisacodyl, significantly induced cell proliferation in almost the entire intestinal epithelia in a clear dose-dependent manner. DSS also induced cell proliferation in some portions at high doses. Increase in BrdU-labelling indices was correlated well with the severity of inflammatory changes in the intestinal mucosa as well as with purging effects of stimulant laxatives and DSS. In contrast, the bulk-forming laxative CMC-Na did not consistently enhance cell proliferation nor cause apparent cytotoxicity in the intestine despite exerting remarkable purging effects. 1-HAQ and MgSO4 slightly induced cell proliferation in the cecum and the colorectum, although there was little or no intestinal cytotoxicity. Pectin and NaCl did not influence cell kinetics of the epithelia, nor cause any inflammatory changes in the mucosa. Our results thus indicate that diarrhea caused by laxatives is not necessarily correlated with induction of cell proliferation, as in the intestinal mucosa, and that inflammatory changes followed by regenerative process could be responsible for enhancing cell kinetics. Although the precise significance of cell proliferation in carcinogenesis remains unclear, it is crucial for setting doses of carcinogenicity testings that charges in cell kinetics caused by chemicals be taken into account.
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PMID:Cell proliferation induced by laxatives and related compounds in the rat intestine. 806 33

Abnormalities of the p53 gene are frequently observed in human tumors, including urinary bladder carcinoma, suggesting that p53 plays an important role in human carcinogenesis. However, its role in rat bladder carcinogenesis is unclear. In this study, we investigated the presence of p53 mutations in 122 urinary bladder tumors induced in F344 rats in the following carcinogenesis models: (i) 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT; 6 weeks) in the diet followed by 3% or 5% sodium saccharin in the diet, 5% sodium ascorbate, 3.12% calcium saccharin (CaSac), 1.34% sodium chloride (NaCl), 5.2% CaSac plus 1.34% NaCl, or basal diet alone (72 weeks); and (ii) 0.2% FANFT, 0.05% N-(4-hydroxybutyl)nitrosamine in the drinking water, N-methyl-N-nitrosourea 20 mg/kg body wt, i.p. twice per week, or basal diet alone (4 weeks), followed by 3% uracil in the diet (20 weeks). Polymerase chain reaction-single-strand conformation polymorphism analysis and direct sequencing were performed for exons 5-8 in the rat p53 gene. We found nine tumors (7.4%) with p53 mutations. Two tumors had two mutations in the p53 gene. The tumors that had p53 mutations were relatively smaller than those that did not have p53 mutations. There were no mutation clusters among the treatments or hot-spots for p53 mutations. These results indicate that p53 mutation is infrequent in bladder carcinogenesis in rats, and when it does occur, it does not appear to provide a growth advantage.
Carcinogenesis 1994 Mar
PMID:p53 mutation is infrequent and might not give a growth advantage in rat bladder carcinogenesis in vivo. 811 28

The role of short chain fatty acids (SCFA) in murine colonic carcinogenesis (MCC) has not yet been clarified. In rats, Freeman et al have reported an increased number of colonic tumors induced with dimethylhydrazine (DMH) and sodium butyrate in drinking water. On the other hand, Deschner et al showed that tributyrin intake did not increase MCC induced with azoxymethane. Both of them have reported high levels of fecal butyric acid with sodium butyrate and tributyrin intake. Although salt intake has been positively associated with colorectal cancer some authors do not support this association. We have evaluated the influence of right hemicolectomy (RH) (right colon as main source of SCFA) and the intake of 2%-pH 7 sodium butyrate (S.BUT) and 4 g/l sodium chloride (S.CHL) in drinking water, in MCC. Forty eight male Wistar rats weighing 150 g were divided into 4 groups: RH, S.BUT, S.CHL, control (C). Half of the animals received weekly DMH 20 mg/kg subcutaneously for 12 weeks. Necropsy was performed after 6 months. We have determined fecal SCFA content by gas chromatography. Neoplasm was present in 70% of rats treated with DMH. The number of animals with tumors was: RH 4/6, S.BUT 4/6, S.CHL 3/5, C 6/6. Tumor frequency was: RH 1.17 +/- 0.48, S.BUT 1.50 +/- 0.76, S.CHL 1.20 +/- 0.49, C 1.50 +/- 0.22. S.BUT group, treated with DMH, presented a lower butyric acid concentration (p < 0.05) in comparison with other groups. We have no explanation for this finding; gastric absorption of sodium butyrate may be an important factor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Influence of sodium butyrate intake on murine colonic carcinogenesis]. 829 30

Short-term assays in vivo have suggested that hickory smoke condensate (HSC), a food flavouring, might have tumour-initiating and/or promoting activities in the glandular stomach of the rat. In the present study, the modifying effects of HSC on glandular stomach carcinogenesis after initiation with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride (MNNG salt) were investigated in male Wistar rats. Animals were given MNNG solution (100 ppm) as drinking water and simultaneously fed the diet supplemented with 5% sodium chloride for 8 wk. Matched negative controls received neither MNNG nor sodium chloride. Rats were then fed a basal diet and given HSC solution (1 or 3%) or tap water for the following 32 wk. During the experimental period, treatment with MNNG salt and administration of HSC both brought about growth retardation although the final body weight of rats was comparable between groups. Only two rats treated with MNNG salt followed by 1% HSC developed adenocarcinoma of the stomach. HSC treatment appeared to increase the number of rats with preneoplastic hyperplasias and/or adenocarcinomas in both the fundic and pyloric mucosa, although not to a statistically significant extent. HSC administration significantly increased malondialdehyde levels in the urine and gastric mucosa, the former in a dose-dependent manner. The results suggest that HSC has little, if any, promoting effect on two-stage glandular stomach carcinogenesis in rats when given during the post-initiation phase. However, the tumour co-initiating effects of HSC require further clarification.
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PMID:Effects of hickory smoke condensate on gastric carcinogenesis in Wistar rats after treatment with N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride. 844 84

The modifying effects of 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3], a vitamin D3 derivative, on glandular stomach carcinogenesis were investigated in male Wistar rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride exposure during the postinitiation phase. A total of 130 male 6-week-old rats was divided into five groups. Groups 1-3 (consisting of 30 rats/group) were given MNNG in drinking water at a concentration of 100 ppm and were simultaneously fed a diet supplemented with 10% NaCl for 8 weeks. They were fed a diet containing either 5.0 ppm (group 1) or 2.5 ppm (group 2) 24R,25(OH)2D3 or were kept on the basal diet alone (group 3) for the following 57 weeks. Rats in groups 4 and 5 were given 24R,25(OH)2D3, as were animals in groups 1 and 3, but did not receive the MNNG + NaCl treatment. The total incidence of combined atypical hyperplasias and adenocarcinomas in the glandular stomachs was significantly lower in group 1 (24%) than in group 3 (70%; P < 0.01). The mean numbers of atypical hyperplasias or adenocarcinomas of the glandular stomachs in groups 1 (0.31) and 2 (0.66) were also significantly decreased (P < 0.01 and P < 0.05, respectively) as compared to the group 3 value (1.21). Thus, the development of cancerous and precancerous lesions in the glandular stomach was decreased by exposure to 24R,25(OH)2D3 in a dose-dependent manner. Urinary calcium levels were increased by this vitamin D3 derivative (in line with the applied dose) when assayed at 10, 30, and 62 weeks, regardless of the MNNG + NaCl treatment The present results clearly indicate that 24,25(OH)2D3 exerts chemopreventive effects, possibly by influencing calcium pharmacodynamics, when given during the postinitiation phase of glandular stomach carcinogenesis in rats.
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PMID:Chemopreventive effects of 24R,25-dihydroxyvitamin D3, a vitamin D3 derivative, on glandular stomach carcinogenesis induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride. 866 11

The effects of oral calcium chloride (CaCl2) on sodium chloride (NaCl)-enhanced induction of gastric carcinogenesis by the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine, and the norepinephrine (NE) concentration in the gastric wall, were investigated in Wistar rats. Animals were given the carcinogen for 25 weeks and then chow pellets containing 10% NaCl with or without 8% or 4% CaCl2. In week 52, the incidence of gastric cancers, the NE concentration in the antral portion of gastric wall and the labelling index of antral epithelial cells were significantly greater in rats fed NaCl alone than in untreated control rats. Concomitant oral treatment with CaCl2 at 8%, but not 4%, significantly reduced the incidence of gastric cancers, the NE concentration in the antral portion of gastric wall and the labelling index of the antral epithelial cells in week 52 compared with those in rats fed NaCl alone. Because NE concentration reflects sympathetic nervous system activity, our findings suggest that the sympathetic nervous system could play a role in NaCl-enhanced gastric carcinogenesis. Our findings also suggest that NE depletion by CaCl2 may be related to its inhibition of NaCl-enhanced carcinogenesis.
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PMID:Tissue norepinephrine depletion as a mechanism for calcium chloride inhibition of gastric carcinogenesis in rats after treatment with N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride. 869 May 17

The customary salting and pickling of fish in high risk gastric cancer regions were modeled to explore the relevant causative chemicals. The fish Sanma hiraki was treated with sodium chloride and sodium nitrite at pH 3. Previously, it had been found that an extract of the treated fish was mutagenic in Salmonella typhimurium TA 1535 without S9 and also that it induced glandular stomach cancer upon gavage to rats. We now demonstrate that the mutagenicity was enhanced by preincubation of the raw meat for several days before salt-nitrite treatment. HPLC techniques showed that three mutagens were present in the fish extract. One of the mutagens was found to be stable over the pH range of 1.0-9.0. This mutagen was purified by silica gel solid phase extraction, followed by a series of reverse phase HPLC steps, and was characterized by low and high resolution MS, NMR, and FT-IR. While N-nitroso compounds were generally believed to be associated with gastric carcinogenesis, it was unexpectedly found that the mutagen has the novel structure 2-chloro-4-methylthiobutanoic acid (CMBA). Based on the structure, it seemed likely that methionine might be the precursor, and this was, indeed, proven. Both salt and nitrite are essential factors for forming this mutagen. The yield of CMBA was linear for chloride concentrations from 0 to 800 mM NaCl. Of 20 amino acids reacted with nitrite and chloride at pH 3, only methionine generated a mutagen for S. typhimurium TA 1535. Tryptophan gave a product mutagenic in S. typhimurium TA 100 and TA 98, but not TA 1535, and in the case of tyrosine, the mutagen was active only for TA 100. These results suggest an important role for salt in gastric carcinogenesis and provide new approaches for exploring the formation of mutagens/carcinogens for specific target organs.
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PMID:Gastric carcinogenesis: 2-chloro-4-methylthiobutanoic acid, a novel mutagen in salted, pickled Sanma hiraki fish, or similarly treated methionine. 892 17

The modifying effects of Chelidonium majis L. (Papaveraceae) herb extract (CH), an analgesic traditionally prescribed for gastric and duodenal ulcer patients, on gastric tumor development were studied in rats given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Sixty-four male 6-week-old Wistar rats were used. Group 1 rats were initially given MNNG (200 mg/kg b.w.) by gavage at days 0 and 14 as well as saturated sodium chloride solution (S-NaCl, 1 ml per rat) every 3 days during weeks 0-3 (six times), and then placed on basal diet containing 0.1 or 0.2% CH for 16 weeks from week 4. Rats of Group 2 and 3 were treated with MNNG together with S-NaCl or saline (0.9% NaCl, 1 ml per rat), respectively, timed as in Group 1 but without further treatment. All surviving animals were killed at week 20 and histopathologically investigated. In the glandular stomach, the number of preneoplastic pepsinogen 1 altered pyloric glands (PAPGs) in the MNNG + S-NaCl-->CH (0.1%) group (Group 1) was significantly smaller than in the MNNG + S-NaCl group (Group 2) (P < 0.02). The incidences of forestomach neoplastic lesions (papillomas and squamous cell carcinomas) also showed a tendency to decrease with the CH treatment. The results thus indicate that CH exerts inhibitory effects on glandular stomach carcinogenesis in the rat, so that it may have potential as a chemopreventive agent for stomach cancer in man.
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PMID:Potential preventive effects of Chelidonium majis L. (Papaveraceae) herb extract on glandular stomach tumor development in rats treated with N-methyl-N'-nitro-N nitrosoguanidine (MNNG) and hypertonic sodium chloride. 906 29


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