methylnitronitrosoguanidine and Atrophy

To explore the changes of Sonic Hedgehog (Shh) signaling pathway in the stomach mucosa during the formation of gastric precancerous lesions.. A total of 72 suckling rats in half genders were randomly and equally divided into the normal group and model group. The rats in the model group were administered with 0.1 ml 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) at the dosage of 800 mg/L for 10 days, whereas the rats in the normal group were similarly administered with normal saline. A total of 12 rats in each group were killed at the end of 10th, 22nd, and 34th weeks in half gender, respectively. Histopathological changes of the gastric mucosa were observed by hematoxylin and eosin (HE) staining; the levels of Shh, Ptch1, Smo, Gli1, Gli2, Gli3, SuFu, Cyclin D1, Cyclin E1, c-Myc, and β-actin mRNAs in the gastric mucosa were determined by real-time polymerase chain reaction; while the protein expression of Shh, Ptch1, Smo, Gli1, SuFu, Cyclin D1, Cyclin E1, c-Myc, and p-c-Myc was detected by western blot analysis.. With the development of atrophy and dysplasia of gastric mucosa, the levels of Shh, Smo, Gli1, Cyclin D1, Cyclin E1, and c-Myc mRNAs increased, while those of Ptch1 and SuFu decreased. The expression of Shh, Smo, Gli1, Cyclin D1, Cyclin E1, and p-c-Myc proteins were elevated, while the expression of Ptch1 and SuFu proteins were decreased, however, without statistical difference.. Shh signaling is activated during the formation of gastric precancerous lesions, which indicates that the Shh signaling pathway participates in the development and progression of gastric precancerous lesions.

Topics: Animals; Atrophy; Disease Models, Animal; Female; Gastric Mucosa; Gene Expression Regulation, Neoplastic; Hedgehog Proteins; Male; Methylnitronitrosoguanidine; Precancerous Conditions; Rats, Sprague-Dawley; RNA, Messenger; Signal Transduction; Stomach Neoplasms; Time Factors

Although we have previously showed that a selective cyclooxygenase-2(COX-2) inhibitor celecoxib prevents gastric cancer development in a rat model of gastric carcinogenesis, the role of celecoxib on gastric premalignant lesions remains unknown. This study was to explore whether celecoxib was effective for the prevention of premalignancy, and further to clarify its mechanism.. Ninety-four male Wistar rats were divided into 5 groups. Group A (n=12) was fed with water only; group B (n=16) with daily 10 mg/kg celecoxib; group C (n=22) with 100 microg/ml N-methyl-No-nitro-N-nitrosoguanidine (MNNG); group D (n=22) with 100 microg/ml MNNG and daily 10 mg/kg celecoxib; group E (n=22) with 100 microg/ml MNNG and daily 3 mg/kg indomethacin. The rats in groups B to E were given 10% sodium chloride in the initial 6 weeks, and the rats in groups C to E were given 100 microg/ml MNNG in drinking water to induce premalignant lesions in the stomach. Six rats in group A, 8 in group B, 10 in group C, 10 in group D, and 10 in group E were killed at week 16, and others were killed at week 24. The occurrence rates of gastric premalignant lesions in the groups were compared. The mRNA and protein levels of COX-1 and COX-2 in gastric mucosa were determined by real-time polymerase chain reaction (PCR) and immunohistochemistry; prostaglandin E2 (PGE2) level was measured by an ELISA-based assay.. Ninety-three rats were studied. In week 16 and week 24, the occurrence rates of glandular atrophy in groups C, D, and E had no significant difference (P>0.05). In week 16, gastric mucosal dysplasia was not detected in groups C, D, and E; at week 24, the occurrence rates of dysplasia were 75% (9/12) on group C, 25% (3/12) in group D, and 46% (5/11) in group E. The occurrence rate of gastric mucosal dysplasia was significantly lower in group D than in group C (25% vs. 75%, P=0.039); there was no significant difference between group E and group C (46% vs. 75%, P=0.214). At week 16 and week 24, there was no significant difference in COX-1 expression between treatment groups and control group. The mRNA and protein levels of COX-2 in group C (3.29+/-1.50 and 3.41+/-0.94) were significantly higher than those in other groups (P<0.001). There was no significant difference in PGE2 level between groups C, D, and E (P>0.05).. Celecoxib effectively inhibits the development of gastric mucosal dysplasia in rats induced by MNNG, but has no effect on the PGE2 level in the gastric mucosa, indicating that the anti-neoplastic activities of celecoxib may be independent of COX-2.

Topics: Animals; Atrophy; Celecoxib; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dinoprostone; Gastric Mucosa; Male; Methylnitronitrosoguanidine; Precancerous Conditions; Pyrazoles; Random Allocation; Rats; Rats, Wistar; RNA, Messenger; Stomach; Stomach Neoplasms; Sulfonamides

Several studies have been reported on the effects of various therapeutic agents in enhancing or suppressing the carcinogenic activity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). However, it is still unknown whether a mucosal protective agent could suppress its carcinogenic activity.. Twenty-five Wistar male rats were divided into four groups: group 1, MNNG alone; group 2, MNNG + tetraprenylacetone; group 3, control; group 4, tetraprenlacetone alone. MNNG 100 mg/mL, was freely given to groups 1 and 2, and tetraprenylacetone (200 mg/kg intraperitoneal) was additionally administered every other day to the rats in groups 2 and 4. The animals were sacrificed at 10 weeks and the gastric mucosa examined.. Atrophic changes were observed in the antrum after 8 weeks of oral administration of MNNG. Furthermore, using immunohistological analysis with 5-bromo-2'-deoxyuridine (BrdU), the proliferative zone was found to be enlarged and shifted upward, although the BrdU labelling index of the proliferative zone was unaltered. Intraperitoneal administration of tetraprenylacetone every other day suppressed the MNNG-induced atrophic change and the alterations proliferative markers. Tetraprenylacetone alone did not have an effect either on morphological or proliferative markers.. These observations suggest that gastric mucosal defensive factors may play critical roles in suppressing atrophic change inducing carcinogenesis by an exogenic carcinogen.

Topics: Animals; Anti-Ulcer Agents; Atrophy; Carcinogens; Diterpenes; Gastric Mucosa; Male; Methylnitronitrosoguanidine; Rats; Rats, Wistar

Hickory-smoke condensate (HSC) is a popular food flavouring in the USA. Available data have suggested that this food additive has tumour-initiating/promoting potential. Accordingly, a commercial HSC has been investigated for its capacity to promote tumours in the rat glandular stomach using pepsinogen 1 (Pg 1)-altered pyloric glands (PAPG) as the marker of preneoplastic lesions. The development of PAPG initiated by a single intragastric administration of N-methyl-N'-nitroso-N-nitrosoguanidine was significantly increased by feeding rats a diet containing 5% HSC; no effect was observed with lower doses (1.25 or 2.5%) of HSC. The results suggest that HSC has weak tumour-promoting potential in the rat glandular stomach.

Topics: Animals; Atrophy; Food Additives; Gastric Mucosa; Hyperplasia; Immunoenzyme Techniques; Male; Methylnitronitrosoguanidine; Pepsinogens; Pyloric Antrum; Rats; Rats, Inbred WKY; Smoke; Stomach Neoplasms; Wood

The effects of gastrin on the histopathology of the glandular stomach and on the incidence of gastric carcinoma induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in inbred Wistar (W) rats. Prolonged administration of gastrin after treatment with MNNG significantly reduced the incidence of adenocarcinomas of the glandular stomach. In addition, atypical glandular proliferations were significantly less frequent and were smaller, and the incidence of marked mucosal atrophy was significantly reduced in both the antral and oxyntic gland mucosae. Both atypical glandular hyperplasia and mucosal atrophy are precursors of gastric cancers; prolonged administration of gastrin to rats after treatment with MNNG suppressed development of precursors of gastric cancer and so prevented development of gastric cancers.

Topics: Adenocarcinoma; Animals; Atrophy; Delayed-Action Preparations; Drug Interactions; Gastric Mucosa; Gastrins; Male; Methylnitronitrosoguanidine; Rats; Rats, Inbred Strains; Stomach; Stomach Neoplasms

Topics: Animals; Atrophy; Autoradiography; Gastrectomy; Gastric Mucosa; Histocytochemistry; Hyperplasia; Male; Methylnitronitrosoguanidine; Postoperative Complications; Rats; Stomach Neoplasms; Time Factors