Gastric Carcinogenesis In Rats Research Articles

Rosmanol Triggers Apoptosis Against MNNG-induced Gastric Carcinogenesis in Rats through Attenuation of the P13K/AKT/HMBG1 Signaling Pathway.

Gastric cancer (GC) is a frequent malignant neoplasm found in China. Despite numerous therapeutic methodologies to ameliorate the well-being of GC patients, their efficiency remains inadequate. Rosmanol (RML) is a phenolic diterpene compound with antioxidant and anticancer activities. In the current research, the apoptotic efficacy of RML on methylnitronitrosoguanidine (MNNG)-induced GC model was determined. The rats were allocated into four sets, viz., normal control, MNNG (200 mg/kg bw) + NaCl, MNNG + RML (20 mg/kg), and RML (20 mg/kg) orally treated for 20 weeks. The results exposed that GC rats revealed higher (P<0.05) levels of TBARS and reduced antioxidant status in the stomach and liver tissues counter to other groups. In contrast, the TBARS level was substantially alleviated (P<0.05) and restored the antioxidant status in RMLadministered rats. Histopathologic assessment of gastric tissue unveiled that an MNNG-induced group presented squamous cell carcinoma with keratin pearls. The administration of RML reduced GC incidence, and only mild dysplasia was observed. Further, RML alleviated Bcl-2, P13K, AKT, and HMGB1, as evidenced by RT-PCR and Western blot analysis. Furthermore, RML triggered caspase-mediated mitochondrial apoptosis through the inactivation of the PI3K/AKT/HMGB1 pathway, eventually leading to GC cell death. This highlights that RML may be a potential natural antioxidant employed as a chemoprotective agent in GC rats.

Chemoprotective Effect of Scutellarin against Gastric Cancer in Rats: An in vitro and in vivo Study.

This study evaluated the chemoprotective effect of scutellarin (SC) in vitro and in vivo against gastric carcinogenesis in rats and celllines and examined the underlying mechanism. Gastric cancer celllines (AGS) was used for the in vitro study and lactate dehydrogenase (LDH) profile, histone deacetylase (HDAC) assay, cell cycle & apoptosis ratio and antioxidant parameters were measured. N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was used to induce gastric carcinogenesis in rats and the rats received the different doses of SC (10, 20 and 30 mg/kg). The body weight and tumor incidence were measured at regular time intervals. The antioxidant and pro-inflammatory cytokines were estimated. The finding of data showed that the drug was effective against AGS cell line. Supplementation of scutellarin revealed an upregulation in body weight compared with the MNNG group rats. Moreover, it also reduced the incidence of tumor. It also altered the significant DNA density, LDH content, mucus content and acidity. Scutellarin treated rats showed improved activity in enzymatic and non-enzymatic antioxidant profile and reversed the content of cytokines compared with MNNG induced gastric cancer group rats. This research reveals the chemoprotective property of the scutellarin and highlights the promising role of drug by alteration of inflammatory pathway by minimizing its adverse effect.

Dysbiosis of gut microbiota is associated with gastric carcinogenesis in rats

ObjectivesAlthough many studies have examined changes in gut microbiota composition in gastric carcinogenesis to clarify the mechanism of action of anticancer drugs, it is unclear whether animal models of gastric carcinogenesis adequately reflect the disease in humans. MethodsTo address this issue, the present study investigated changes in the gut microbiome profile of a rat model of gastric carcinogenesis established using a combination of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), sodium salicylate, irregular fasting, and ranitidine. The rats were divided into control (Normal), chronic non-atrophic gastritis (CNAG), chronic atrophic gastritis (CAG), precancerous lesion of gastric cancer (PLGC), and gastric cancer (GC) groups according to histopathological features. Gut microbiome in gastric carcinogenesis profiling was performed by 16S rRNA gene sequencing of rat feces samples. ResultsWe found that gut bacterial species richness increased whereas species diversity decreased during gastric carcinogenesis, with the most significant changes detected in the PLGC group. Gut microbiota community composition differed across groups, with the greatest similarities observed between CNAG and CAG groups and between PLGC and GC groups. There were significant differences in taxonomic representation at the phylum level: the PLGC group had the highest ratio of Firmicutes/Bacteroidetes whereas the GC group had the highest abundance of Proteobacteria and Actinobacteria. ConclusionsThese results indicate that changes in the gut microbiome in a rat model of MNNG-induced gastric carcinogenesis are similar to those observed in humans, thus providing a useful tool for evaluating the efficacy and mechanism of action of novel monotherapies or drug combinations for the treatment of gastric carcinogenesis.

Diosmin Regulates Oxidative Stress and Inflammatory Marker Levels in N-Methyl-N-Nitrosourea-Induced Gastric Carcinogenesis in Rats.

Gastric cancer is the most typical oncological illness globally. Though the incidence of gastric cancer has dropped dramatically over the last few years, the survival rate is yet concerning due to poor diagnostic strategy. The etiology of gastric cancer is majorly associated with dietary factors. For this reason, application of nontoxic natural agents with anticancer effects for patients is needed. Diosmin has been commonly utilized to treat various diseases both traditionally and now clinically. However, its effect on gastric carcinogenesis remains unclear. The effects of diosmin were used to evaluate how N-methyl-N-nitrosourea (MNU) induces gastric carcinogenesis in rats. The general and gross assessment of MNU in experimental animals was tabulated. Biological tumor markers (gastrin, ALP, LDH, and γ-GT) were examined. Oxidative markers (LPO) and antioxidative markers (GSH, vitamin E, and vitamin C) were determined. In addition, inflammatory cytokines (thioredoxin, glutaredoxin, NF-κB, TNF-α, IL-6, PGE2) were explored and justified with histopathological studies. Overall, the results showed positive anticancer activity demonstrated by improved body weight, reduced tumor rate, decreased oxidative marker value by increased antioxidative rate, and suppressed tumor biomarkers and inflammatory cytokines. The histopathological analysis was congruent with the data observed. Our conclusion that diosmin exerts its anticancer activity by up-regulation of antioxidants which might be responsible for amelioration of oxidative stress and inflammatory cytokines in carcinogenesis to prevent gastric cancer.

Leptin enhances N-methyl-N’-nitro-N-nitrosoguanidine (MNNG)-induced tumour growth in gastric mucosa of male Sprague-Dawley rats

Individuals who are obese are at a greater risk of developing gastric cancer. They are however also hyperleptinaemic. Chronic leptin treatment has been shown to upregulate numerous cancer-causing genes in the stomach of male Sprague-Dawley rats. It is however unclear if leptin enhances the effect of gastric carcinogens in vivo. This study was therefore done to investigate the effect of leptin on gastric carcinogenesis in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Twenty-four, 6-week old male Sprague-Dawley rats were divided equally into three groups: G1 served as age-matched controls; G2 was treated with MNNG in drinking water ad libitum (200mgL-1); G3 was given leptin and MNNG. Rats were euthanized after 40weeks of treatment and their stomachs were removed for histopathology, microarray, and RT-qPCR analysis. Fisher's exact test and one-way ANOVA were used to analyse the data. Fifty percent of the MNNG-treated rats developed gastric hyperplasia (p < 0.05), but there was no significant change in any carcinogenic genes. Concurrent MNNG and leptin treatment however induced hyperplasia, dysplasia, hypertrophy, and adenocarcinoma in 75% (6/8) of the rats; with upregulation of microRNAs, olfactory receptors, Hey2 (transcription factor), Tmed2 (vesicular trafficking), and Lcn11 (cell proliferation) genes. It appears that leptin enhances MNNG- induced tumour growth in stomachs of Sprague-Dawley rats and its role in gastric cancer requires further scrutiny.

The Protective Effect of Curcumin against Nitrosamine-Induced Gastric Oxidative Stress in Rats.

Curcumin has a wide spectrum of biological, pharmaceutical, and antioxidant effects in cancer experimental models. Nitrosamine is commonly used as an experimental oxidizing agent which induces gastric oxidative stress and gastric carcinogenesis in rats. We examined the antioxidant potential effect of curcumin against nitrosamine-induced gastric oxidative stress in rats. Forty Sprague-Dawley rats were randomly divided into 4 groups (10 rats/group). The control group was fed a standard diet and received a single dose of normal saline, the nitrosamine-treated group was fed a standard diet and received an intraperitoneal injection of nitrosamine at a single dose of 100 mg/kg body weight (b.w.). The other two groups received a daily dose of curcumin (200 mg/kg b.w.) via intra-gastric intubation in the presence or absence of nitrosamine injection. After 16 weeks, all rats were sacrificed, and the gastric tissues were dissected for histopathological examination and for biochemical measurements of oxidative stress indices. Our results showed that nitrosamine causes oxidative stress in gastric tissues as evidenced by glutathione depletion, increased level of lipid peroxides, nitric oxide release, impairment of total antioxidant capacity, DNA oxidative damage, and inhibition of antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase). Histopathological findings revealed abnormal gastric architecture in association with nitrosamine injection compared to the non-treated control group. Curcumin significantly suppressed the gastric oxidative damage associated with nitrosamine treatment and mitigated its histopathological effect. These results suggest that curcumin, as an antioxidant, has a therapeutic effect against oxidative stress-mediated gastric diseases.

Effect of Dendrobium officinale Extraction on Gastric Carcinogenesis in Rats.

Dendrobium officinale (Tie Pi Shi Hu in Chinese) has been widely used to treat different diseases in China. Anticancer effect is one of the important effects of Dendrobium officinale. However, the molecular mechanism of its anticancer effect remains unclear. In the present study, gastric carcinogenesis in rats was used to evaluate the effect of Dendrobium officinale on cancer, and its pharmacological mechanism was explored. Dendrobium officinale extracts (4.8 and 2.4 g/kg) were orally administered to the rats of the gastric carcinogenesis model. Compared with the cancer model group, the high dose of Dendrobium officinale extracts significantly inhibited the rate of carcinogenesis. Further analysis revealed that Dendrobium officinale extracts could regulate the DNA damage, oxidative stress, and cytokines related with carcinogenesis and induce cell apoptosis in order to prevent gastric cancer.

Preventive effect of rebamipide on N-methyl-N′-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats

Chemoprevention strategies against gastric cancer (GC) need to be explored in light of the fact that stomach cancer still occurs in the absence of Helicobacter pylori (HP) infection and following HP eradication. We evaluated the effect of rebamipide on N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced carcinogenesis in SD rats. Thirty-nine male rats were divided into four groups based on whether or not they were treated with rebamipide and/or MNNG: Control, Rebamipide, Control-M, and Rebamipide-M groups. From 8 weeks of age, rats in the Control-M and Rebamipide-M groups received MNNG in drinking water for 30 weeks. The Rebamipide and Rebamipide-M groups were administered 5mg/kg/day of rebamipide. At 50 weeks, cancerous lesions were not observed in either the Control or Rebamipide groups. Nine rats in the Control-M group had developed GC, while four rats in the Rebamipide-M group had developed GC. The incidence of cancer in the Rebamipide-M group was significantly less than in the Control-M group (p<0.05), with a trend toward a lower incidence of invasive carcinoma in the Rebamipide-M group. Carcinomatous invasion into the muscularis propria was not observed in the Rebamipide-M group. In conclusion, the present study demonstrates that rebamipide suppresses. MNNG-induced carcinogenesis and may also inhibit progression of cancer in rats.

New experimental model of gastric carcinogenesis in rats with the use of formaldehyde and hydrogen peroxide mixture

This study was designed to develop an animal model of gastric cancer by using a mixture of formaldehyde and hydrogen peroxide. Thirty‐five outbred rats were used. In experimental group, 1.0 ml of the formaldehyde (0.4%) and hydrogen peroxide (0.4%) mixture (1:1) were administered to 30 rats by intragastric gavage on the 1st and 3rd day every 2 weeks for 6 months. Five non‐treated rats served as a control. The mortality rate among treated rats was 13.3%. We found that 6 months after the onset of treatment the 4 of 5 rats had gastric tumor, while after 7.5 months all survived 21 rats showed malignant tumors of the stomach. The tumors were primarily localized within the gastric mucosa, though the invasion of individual tumor cells and their clusters in the muscularis propria and serosa as well as in the lymphatic and blood vessels were also seen. In most cases, the infiltrated gastric mucosa areas (2 to 3) had rigid gastric folds and were 0.7×1.0cm to 1.5×3.0cm in size. We observed signet‐ring cell carcinomas in 80.9% of rats, well‐differentiated tubular adenocarcinoma in 66.6% of rats and moderately differentiated tumors in 23.8% of rats. Metastasis in regional lymph nodes were noted in 3 rats (14.3 %), while 6 animals (28.6%) revealed peritoneal dissemination of the small intestine. In addition, 19.0% of rats showed tumors of the lungs. Therefore, these data demonstrate that our animal model can be used to study gastric carcinogenesis.

Impact of naringenin on glycoprotein levels in N-methyl-N′-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats

We have studied the chemopreventive role of naringenin against experimental gastric carcinogenesis in male Wistar rats. The animals were divided into five groups and six animals were included in each group. Stomach, liver, sera and kidney specimens were collected in the 20th week and the level of glycoproteins namely, hexose, hexosamine, sialic acid and fucose, were measured in the control, gastric cancer-induced, cancer naringenin pretreated, cancer naringenin posttreated and naringenin alone animals. The glycoprotein levels were increased in the gastric cancer-induced rats when compared with the control rats. The levels of glycoprotein were decreased significantly in cancer-bearing rats supplemented with naringenin as compared with the gastric cancer-induced rats. The result shows the gastroprotective effect of naringenin and describes the likelihood of naringenin in maintaining the integrity of cell membranes and gastric mucosa against oxidative damage. Moreover, we hypothesize that regulation of glycoprotein levels by naringenin could be associated with the regression of N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinoma.

Effects of sodium chloride, saccharin, phenobarbital and aspirin on gastric carcinogenesis in rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine.

Sodium chloride, saccharin sodium, phenobarbital sodium and aspirin were tested for tumor-promoting activity in the glandular stomach of rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) coupled with administration of a high salt diet. Male outbred Wistar rats were given MNNG in the drinking water (100 mg/liter) for 8 weeks, and during this period they were fed on diet supplemented with 10% sodium chloride. Thereafter, they were divided into 5 groups and fed on the basal diet or one of various diets supplemented with 10% sodium chloride, 5% saccharin, 0.05% phenobarbital or 1% aspirin until the end of the experiment. All animals were killed at the 40th experimental week for necropsy and histological examination. The incidence of adenocarcinoma was increased in the group given sodium chloride following initiation by MNNG and sodium chloride as compared with the group given MNNG and sodium chloride initiation only, but not significantly. However, the incidence of preneoplastic hyperplasia was significantly increased in this group. Saccharin also enhanced the development of adenocarcinomas of the glandular stomach. The results indicated that dietary administration of sodium chloride or saccharin after MNNG tends to promote tumor development. Phenobarbital or aspirin did not enhance tumor development, aspirin in fact rather showing a tendency to decrease the tumor incidence.

Naringenin reduces tumor size and weight lost in N-methyl-N′-nitro-N-nitrosoguanidine–induced gastric carcinogenesis in rats

Carcinoma of the stomach is reportedly the second most common cancerous condition affecting the general population. Administration of antioxidants is reported to effectively alleviate the risk of gastric carcinoma. Therefore, we assessed the protective role of naringenin, an antioxidant and naturally occurring citrus flavanone, on gastric carcinogenesis induced by MNNG (200 mg/kg body weight) and S-NaCl (1 mL per rat) in Wistar rats (obtained from the Central Animal House Facility, University of Madras, Taramani Campus, Chennai, India). The animals were divided into 5 groups, and the effects of naringenin on simultaneous and posttreated stages of MNNG were tested. Cancer risk was analyzed along with their antioxidant status. The LPO levels in the experimental groups were assessed as an index of oxidative milieu. Altered redox status was subsequently investigated by assaying the superoxide and hydroxyl radicals, the enzymatic antioxidants (SOD, CAT, GPx), and the nonenzymatic antioxidants viz reduced GSH, vitamin C, and vitamin E. In the presence of MNNG, cancer incidence and LPO levels were significantly increased, whereas enzymatic (SOD, CAT, and GPx) and nonenzymatic antioxidant activities (GSH, Vitamins C, and E) were decreased in the treated rats compared with control rats. Administration of naringenin to gastric carcinoma-induced rats largely up-regulated the redox status to decrease the risk of cancer. We conclude that up-regulation of antioxidants by naringenin treatment might be responsible for the anticancer effect in gastric carcinoma.

Preventive effect of fermented brown rice and rice bran on N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats

A number of possible preventive agents for cancers in different organs have been reported, however, little information is available regarding the effective agents for the development of gastric cancers. The rice components are known to be effective for the prevention of the development of cancers. Our group has demonstrated that fermented brown rice by Aspergillus Orzae (FBRA) has chemopreventive potentials in several organs. In this study, we investigated the modifying effects of FBRA exposed during the initiation or post-initiation phase of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in rats. Five-week-old male ACI rats were divided into 7 groups. Groups 1-5 were given oral administration of MNNG (100 mg/l in distilled water) for 24 weeks starting at 6 weeks of age. Groups 2 and 3 were fed a diet containing 5 and 10% FBRA during the initiation phase, respectively, whereas groups 4 and 5 were fed these diets during the post-initiation phase. Group 6 was given a diet containing 10% FBRA throughout the experiment. Group 7 was kept on the basal diet alone and served as an untreated control. Rats were sacrificed at 52 weeks after the start, and the epithelium of the stomach was investigated in detail. Incidence and multiplicity of gastric proliferative lesions of group 1 (MNNG alone) were 61% and 1.67+/-1.57/rat, respectively. Those of group 5 (25%, 0.35+/-0.67) which were given FBRA at a dose of 10% during the post-initiation phase were significantly less than those of group 1. Furthermore, the same group expressed a significantly decreased Ki67-labeling index in the non-lesional gastric epithelium when compared to that of group 1. These results indicate that FBRA inhibits MNNG-induced development of gastric tumors by administration during the post-initiation phase in rats. FBRA is regarded as a promising dietary agent for the prevention of human gastric cancer.

Lanzoprazole promotes gastric carcinogenesis in rats with duodenogastric reflux.

Duodenogastric reflux is known to cause an increased frequency of cancer in the glandular portion of the stomach in rats. Furthermore, it is debated whether inhibition of gastric acid secretion may promote gastric carcinogenesis. In the present study we examined the combined effect of gastroduodenal reflux and acid inhibition with respect to the development of gastric carcinoma in the rat. Following the construction of a gastrojejunostomy in male Wistar rats, half of them were given the proton pump inhibitor lanzoprazole for 1 year. The rats were then killed and the pH in the stomach and gastrin in blood were measured. The stomach was examined macroscopically as well as histologically. Gastrin levels at autopsy were significantly increased in treated rats compared to the control group, confirming an effect of lanzoprazole on gastric acid secretion. Body weight was significantly reduced in the treated rats. Thirty of 79 rats developed gastric cancer, and they were all adenocarcinomas of the Lauren intestinal type. Gastric cancers occurred significantly more often in lanzoprazole-treated rats (50%) compared with controls (27%). Lanzoprazole given orally enhances the carcinogenic effect of duodenogastric reflux in rats.

Influence of Na2SeO3 and gastric endocrine cells on MNNG induced gastric carcinogenesis in rats

Influence of Na2SeO3 and gastric endocrine cells on MNNG induced gastric carcinogenesis in rats

Suppressive effect of irsogladine maleate on N-methyl- N-nitro- N-nitrosoguanidine (MNNG)-initiated and glyoxal-promoted gastric carcinogenesis in rats

The modifying effect of irsogladine maleate (IRG) on N-methyl- N-nitro- N-nitrosoguanidine (MNNG)-initiated and glyoxal-promoted gastric carcinogenesis was examined in male Wister rats. Six-week-old rats were divided into ten groups. Groups 1 through 6 were given MNNG (100 mg/l in drinking water) for 25 weeks from the start of the experiment, whereas groups 7 through 10 received distilled water in the initiation phase as the vehicle treatment. Groups 1 and 8 were kept on the basal diet and distilled water throughout the experiment (55 weeks). Groups 2–8 were given 0.5% glyoxal in the drinking water for 30 weeks from 26th week of the experiment. Group 3 was fed the diet mixed with 100 ppm IRG for 25 weeks from the start of experiment. Groups 4 and 8 were fed the diet mixed with 100 ppm IRG for 30 weeks from 26th week of experiment. Groups 5 and 9 or 6 were given 100 or 25 ppm IRG containing diet, respectively throughout the experiment. Group 10 was given the basal diet and distilled water as the vehicle treated control. Tumors of upper digestive tracts (stomach and duodenum) were developed in groups: 1 (12/17 rats, 71%), 2 (11/12 rats, 92%), 3 (9/16 rats, 56%), 4 (5/12 rats, 42%), 5 (6/15 rats, 40%) and 6 (7/12 rats, 58%). High dose of IRG in initiation and/or promotion phase significantly reduced the incidence of tumors of the upper digestive tracts. The average numbers of the digestive tracts neoplasms in groups 3, 5 and 6 given glyoxal and IRG were less than those in group 2 which received only glyoxal. These results suggest that IRG could be a preventive agent against the occurrence of neoplasms of the upper digestive tract.

Garlic and neem leaf extracts enhance hepatic glutathione and glutathione dependent enzymes during N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG)‐induced gastric carcinogenesis in rats

The protective effect of garlic (Allium sativum L.) and neem leaf (Azadirachta indica A. Juss.) was investigated on hepatic lipid peroxidation and antioxidant status during N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in male Wistar rats. Enhanced lipid peroxidation in the liver of tumour-bearing animals was accompanied by significant decreases in the activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST), gamma-glutamyl transpeptidase (GGT) and reduced glutathione (GSH) levels. Administration of garlic and neem leaf extracts significantly lowered lipid peroxidation and enhanced the hepatic levels of glutathione and glutathione dependent enzymes. We speculate that garlic and neem leaf significantly alter cancer development at extrahepatic sites by influencing hepatic biotransformation enzymes and antioxidants. Copyright © 2000 John Wiley & Sons, Ltd.

Garlic and neem leaf extracts enhance hepatic glutathione and glutathione dependent enzymes during N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in rats.

The protective effect of garlic (Allium sativum L.) and neem leaf (Azadirachta indica A. Juss.) was investigated on hepatic lipid peroxidation and antioxidant status during N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in male Wistar rats. Enhanced lipid peroxidation in the liver of tumour-bearing animals was accompanied by significant decreases in the activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST), gamma-glutamyl transpeptidase (GGT) and reduced glutathione (GSH) levels. Administration of garlic and neem leaf extracts significantly lowered lipid peroxidation and enhanced the hepatic levels of glutathione and glutathione dependent enzymes. We speculate that garlic and neem leaf significantly alter cancer development at extrahepatic sites by influencing hepatic biotransformation enzymes and antioxidants.

Low-protein diet promotes sodium chloride-enhanced gastric carcinogenesis induced by N-methyl- N′-nitro- N-nitrosoguanidine in Wistar rats

Sodium chloride (NaCl) initiates and promotes experimental carcinogenesis in rats. We recently found that a high-protein diet attenuates NaCl-enhanced gastric carcinogenesis in Wistar rats. To investigate the effect of a purified low-protein diet on NaCl-enhanced gastric carcinogenesis induced by N-methyl- N′-nitro- N-nitrosoguanidine (MNNG) in Wistar rats, rats were fed a purified diet with an equalized caloric content containing 1% or 2% NaCl and 25% casein (normal-protein diet) or 10% casein (low-protein diet) after oral treatment with MNNG for 25 weeks. In week 52, neither 1% nor 2% NaCl had a significant effect on gastric carcinogenesis in rats fed a normal-protein diet. However, oral administration of 2%, but not 1%, NaCl significantly increased the incidence of gastric cancers in rats fed a low-protein diet. Oral administration of 2% NaCl also significantly increased the bromodeoxyuridine (BrdU)-labeling index and the ornithine decarboxylase (ODC) activity and decreased apoptosis of gastric cancers in rats fed a low-protein diet. However, 2% NaCl had no significant effect on these three parameters in rats fed a normal-protein diet. These findings indicate that a low-protein diet enhances the effect of NaCl in gastric carcinogenesis and that this enhancement may be mediated by increased cell proliferation and reduced apoptosis of gastric cancers.

Prevention of spontaneous and chemically induced carcinogenesis using activated carbon fiber adsorbent. II. Inhibitory effect of the activated carbon fiber adsorbent ‘Aqualen’ on N-methyl- N′-nitro- N-nitrosoguanidine-induced gastric carcinogenesis in rats

Two-month-old female LIO rats were given N-methyl- N′-nitro- N-nitrosoguanidine (MNNG) with tap water in a concentration of 100 mg/1 for 12 months (groups 1 and 2) or were kept without the carcinogen treatment (groups 3 and 4). From the first day of exposure to MNNG rats from groups 2 and 3 were given activated carbon fiber adsorbent Aqualen® in their diet five times per week together with lab chow in a daily dose of 100 mg/kg of body weight. The experiment was finalized 16 months after first exposure to the carcinogen. The total stomach adenocarcinoma incidence was 43% in group 1 and 39% in group 2, whereas invasive stomach adenocarcinomas occurred in 36% and 8% of rats from groups 1 and 2, respectively ( P<0.05). Tumors other then stomach sites (duodenum and liver) only developed in rats from group 1 (29%). No lesions were observed in rats exposed to Aqualen without MNNG. Thus, our results demonstrate the inhibitory effect of the activated carbon fiber adsorbent Aqualen® on stomach carcinogenesis in rats.