• Korean Journal of Community Nutrition
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• v.4 no.2
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• pp.239-247
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• 1999

Six-week-old Sprague Dawley rats were fed the diets of 20% casein or soy protein. Two weeks after the feeding, hepatocellular chemical carcinogenesis was initiated by diethylnitrosamine(DEN), and promoted by the diet containing 0.01% 2-acetylamino-fluorene(AAF) and two-thirds partial hepatectomy(PH). The animals were sacrificed at 8 weeks after the DEN injection. The area of placetal glutathione S-trnasferase(GST-P) positive foci, the activities of several enzymes in cellualr antioxidant enzyme systems and glucose 6-phosphatase were determined to investigate the mechanism of the anticarcinogenic effect by the dietary proteins. In another set of experiments, the drinking water of rats fed casein was supplemented with 1.5% inositol hexaphosphate(InsP6) to elucidate whether it has the comparable anticancer action of soy protein. The area and number of GST-P positive foci in the soy protein group were significantly(p<0.05) lower than those inthe casein group. The livers of rats fed casein showed moderate fattydegeneration and larger hyperplastic nodules than those of rats fed soy protein. In another set of experiments, the area and number of GST-P positive foci in the rats fed casein supplemented with InsP6 were not significantly different from those in the rats fed casein or soy protein. The lipid peroxidation of rats fed different protein sources showed no significant difference. Glutathione S-transferase(GST) activities were increased significantly(p<0.05) by carcinogen treatment in all dietary groups. Glucose 6-phosphatase(G6Pase) activities were decreased by carcinogen treatment, and hence showed a reverse relationship(r=-0.695, p<0.01) to the GST-P positive foci. Therefore, the activities in the rats fed casein were lower than those in the rats fed soy protein. These results suggest that the soy protein seems to be more anti-carcinogenic than casein by decreasing the preneoplastic lesion and by increasing the membrane stability but inositol hexaphosphate, a component of soy protein, may not be protective against hepatocarcinogenesis.

• Korean Journal of Environmental Biology
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• v.20 no.2
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• pp.173-179
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• 2002

N-nitrosoethylurea (NEU) -induced changes of lipid peroxide content, aldehyde metabolic enzyme activities and antioxidant enzyme activities were examined in cultured rat liver cell. Aldehyde metabolic enzymes tested in this investigation were alcohol dehydrogenase and aldehyde dehydrogenase. Several antioxidant enzymes tested were glutathione transferase, superoxide dismutase, glutathione reductase and catalase. When the cell was exposed with various concentrations of NEU, lipid peroxide content increased about 2.5 fold with 6.25 mM NEU. Maximun 2.3 times higher alcohol dehydrogenase activity was found after NEU treatment. About 2 times higher aldehyde dehydrogenase activity could also be observed. Only slight increases of glutathione transferase and catalase activities occurred with NEU treatment. In addition mnximun 1.5 times higher superoxide dismutase activities and 3 times higher glutathione reductase activities were found after NEU treatment. Therefore, it is likely that the increases of superoxide dismutase and glutathione reductase could contribute in a antioxidative process against NEU toxicity.

• Journal of Nutrition and Health
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• v.38 no.5
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• pp.364-372
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• 2005

This study is designed to examine the effects of dietary supplementation with vitamin E and dehydroepiandrosterone (DHEA) on the formation of preneoplastic lesions in diethylnitrosamine (DEN) induced rat hepatocarcinogenesis. All Weaning male Sprague-Dawley rats were initiated by a single dose of DEN (200mg/kg body weight), subjected to two­thirds partial hepatectomy 3 weeks later and were sacrificed 8 weeks after DEN initiation. Two weeks after initiation, rats were fed Purina purified rodent diet 5053 (Ralston Purina Rat chow, USA) with $1.5\%$ (15,000 IU/kg diet) vitamin E, $0.5\%$ DHEA and both of those supplemented diet for 6 weeks. Placental glutathione S-transferase (GST-P) positive foci, the activities of catalase, total-glutathione peroxidase (GPx) , glutathione reductase (GR), glutathione S-transferase (GST) and thiobarbituric acid reactive substances (TBARS) contents were decreased significantly by vitaimin E supplement. On the other hand GST-P positive foci number, Cu/Zn-superoxide dismutase (SOD) and glucose 6-phosphatase (G6Pase) activities weren't changed by vitamin E supplement. It might suggest that protective effect of vitamin E against hepatocarcinogens is not involved in the formation of the GST-P positive foci but related to the expansion of that. It seemed that vitamin E supplement helped endogenous defense system in carcinogenesis by decreasing TBARS contents, $H_2O_2$, organic peroxides. Therefore, vitamin E seemed to protect cell from free radical damage in carcinogenesis. By DHEA supplement liver weight and liver/body ratio were increased, the area and number of GST-P positive foci, the activities of catalase, GR, total GPx, GST and the TBARS contents were decreased significantly. On the other hand Cu/Zn-SOD and G6Pase activities weren't changed by DHEA supplement. In hepatocarcinogenesis the activities of antioxidant enzymes weren't increased by DHEA supplement. DHEA did not increase the oxidative stress, while DHEA seems to have anticarcinogenic effect in rats hepatocarcinogenesis.

• Journal of Nutrition and Health
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• v.36 no.8
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• pp.785-792
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• 2003

This study is conducted to determine the effects of dietary source of $\omega$3 fatty acids on preneoplastic foci and the glutathione dependent enzymes in rat hepatocarcinogenesis initiated by diethylnitrosamine (DEN). Male Sprague-Dawley rats were fed one of three diets containing 10% (w/w) fats fixed p/s = -1.0 and $\omega$6/$\omega$3 ratio = -0.4 or 4.0 ; fish oil-com oil blended (FC), com oil-beef tallow-fish oil blended (CF), com oil-beef tallow-perilla oil blended (CP), from gestation period. At 10 weeks, animals of experimental groups were injected intraperitoneally with DEN (200 mg/kg body weight) and two-thirds partial hepatectomy was carried out 3 weeks later and were sacrificed 8 weeks after DEN initiation. The area and number of glutathione S-transferase placenta (GST-P) positive foci were significantly decreased in rats fed diets containing fish oil (FC and CF) than those fed perilla oil diet (CP). Fish oil feeding significantly increased the activities of glutathione dependent enzymes. Rats fed diets containing fish oil (FC and CF) significantly increased the glutathione (GSH) content and the activities of glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST). Glutathione dependent enzymes had significantly negative correlation with GST-P positive foci. Glucose 6-phosphatase (G6Pase) was increased in rats feeding fish oil. Thiobarbituric acid reactive substances were not different among groups. Therefore, the preventive effect against hepatocarcinogenesis might be explained by induction of the glutathione dependent enzymes and G6Pase. (Korean J Nutrition 36(8): 785∼792, 2003)

• Journal of Nutrition and Health
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• v.31 no.6
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• pp.1014-1023
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• 1998

The influences of fish oil and different levels of vitamin I supplement on hepatocellular chemical carcinogenesis have been studied. Male Sprague-Dawley rats received diethylnitrosamine (DEN)(200mg/kg body weight) and were subjected to two-thirds partial hepatectomy to induce murine chemical hepatocarcinogenic procedure. Placental glutathione S-transferase(GST-P) positive foci area, antioxidant enzymes(Cu/Zn-superoxide dismutase(SOD), catalase, glutathione reductase (GR), total- glutathione peroxidase (TGPx), glutathione S -transferase (GST)), glucose 6-phosphatase (G6Pase) activities, and lipid peroxidation of microsomes(thiobarbituric acid reactive substances (TBARS)) were measured. Experimental animals were fed 15% corn or fish oil with 0, 40, 1,000, 10,000IU vitamin E /kg diet for 8 weeks. Vitamin E supplements decreased the area of GST-P positive foci in both groups. The higher the vitamin E levels, the smaller the area of GST-P positive foci were noticed. Compared to 0 IU vitamin E, 40 IU in corn oil and 1,000 IU in fish oil groups were effective in decreasing G57-P positive foci area. Fish oil groups tended to have smaller area of GST-P positive foci. fish oil groups showed lower body weight, lower activities of Cu/Zn-SOD and TGPx, higher TBARS contents, higher activities of GST, catalase, G6Pase, GR and higher liver/body ratio than corn oil groups. As the level of vitamin I increased, GST-P positive foci count, catalase activities, and TBARS tended to decrease. G6Pase activities tended to increase in both groups. At higher vitamin E levels, GST activities tended to decrease in fish oil groups. These results suggest that vitamin I has suppressive offects on hepatocellular chemical carcinogenesis probably through antioxidant eH:cts decreasing TBARS contents, $H_2O$$_2$, and organic peroxides. fish oil tended to have greated suppressive offects than corn oil on hepatocellular carcinogenesis. (Korean J Nutrition 31(6) : 1014-1023, 1998)

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.5
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• pp.782-787
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• 2002

This study was done to investigate the effects of Korean mistletoe water extract and lectin on the apoptosis and preneoplastic lesion in chemically induced rat hepatocarcinogenesis. To attain the above objectives, weanling Sprague-Dawley male rats were fed modified AIN-76 diets containing 10% corn oil for 9 weeks. One week after feeding starts, rats were intraperitoneally injected twice with a dose of diethylnitrosamine (DEN, 50 mg/kg body weight (BW). Rats were provided with 0.05% phenobarbital (PB) in drinking water from one week after DEN treatment until the end of experiment. During the period of PB treatment, rats were injected with mistletoe extract (100 $\mu\textrm{g}$/kg BW) and lectin (10 $\mu\textrm{g}$/kg BW) twice a week. At the end of 9th week, rats were sacrificed and the formation of hepatic glutathione S-transferase placental form positive (GST-P$^{+}$) foci, apoptosis, DNA fragmentation and apoptosis related proteins were determined respectively. The formation of GST-P$^{+}$foci was significantly decreased by mistletoe extract or lectin treatment. Although there was no effect on apoptosis and DNA fragmentation in hepatic tissue by mistletoe extract or lectin treatment, caspase-9 and fas-L were increased. These results suggest that Korean mistletoe extract and lectin have a potential to inhibit hepatocarcinogenesis by increasing apoptosis.sis.

• Journal of the Korean Society of Food Culture
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• v.5 no.1
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• pp.169-180
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• 1990

An experimental study on the effect of milk diet on carcinogenesis induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) was designed in rats to elucidate its mechanism. A total of 136 Sprague-Dawley rats were divided into 6 groups according to the milk dosagnes in each diet. The entire group of 136 rats was fed the MNNG (100 g/ml) and milk for the initial 28 weeks. Thereafter for the next 12 weeks the group was fed a normal diet only. After this 40 week experiment 109 rats survived. These rats were then dissected with the results being summarized as follows: Suppression of gastroduodenal malignancy was evidenced by the increase of milk concentration in the diet except for the group given MNNG and the lowest concentration of milk (6% milk). Significant differences in the rate of cancer association were present between the regenerative hyperplasia (22.2%) and adenomatous hyperplasia (57.9%). The incidence of benign lesions increased proportionally with the concentration of milk in the diet, especially in regenerative hyperplasia. In the group which had been given the lowest concentration of milk there was a significant increase of the serum gastrin level in the rats with gastric cancer or precancerous benign lesions like regenerative hyperplasia or adenomatous hyperplasia.

• Journal of Nutrition and Health
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• v.38 no.1
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• pp.20-29
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• 2005

This study is conducted to determine the effects of dietary levels of corn and tuna oils on the formation of preneoplastic lesions in die-thylnitrosamine (DEN) induced rat hepatocarcinogenesis. Weanling male Sprague-Dawley rats were fed 2.5, 5, 15, 25% (w/w) corn or tuna oils. Hepatocellular carcinogenesis was induced by DEN (200 mg/kg body weight) and two-thirds partial hepactectomy was carried out 3 weeks later and were sacrificed 8 weeks after DEN initiation. Tuna oil group showed smaller area of placental glutathione S-transferase (GST-P) positive foci than com oil group. Com oil group of 25% (w/w) showed the widest area of GST -P positive foci, and tuna oil group showed significantly smaller area of GST-P positive foci than com oil in 25% (w/w) level but had no differences between oil levels. Thio-barbituric acid reactive substances (TBARS) content was the highest in 25% (w/w) level of tuna oil group fed long chain and highly polyunsaturated fatty acids. Also serum ${\gamma}$ -glutamyltranspeptidase (GGT) activities in 25% level of tuna oil group were significantly higher than by other levels. As oil contents increased, glucose 6-phosphatase (G6Pase) seems to decrease in com oil groups but remained the same in tuna oil groups. Glutathione reductase (GR) activities were significantly higher in tuna oil group, and the higher the level of tuna oil, the higher GR activities. But Cu/Zn superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities didn't seem to be influenced by levels and kind of dietary fats. Therefore, as oil levels increased, com oil rich in n-6 fatty acids promoted carcinogenesis but tuna oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of n-3 fatty acids suppressed. Although lipid peroxidation products were elevated in 25% (w/w) tuna oil group, GST-P positive foci didn't increase. Therefore pre-neoplastic lesions might be reduced through mediation of a lipid peroxidation process in tuna oil. As fat contents of tuna oil increased, elevated GR activities may give a rise to produce more reduced glutathione in order to protect against free radical attack, and high G6Pase activities remained the same and they contributed to membrane stability. So tuna oil diet seems to protect hepatocarcinogenesis.

• Journal of Gastric Cancer
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• v.10 no.1
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• pp.1-4
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• 2010

Purpose: Gastric epithelial dysplasia (GED) was defined as "unequivocally neoplastic epithelium that may be associated with or give rise to invasive adenocarcinoma" and GED also represents a direct precursor of intestinal type adenocarcinoma of the stomach. The recommended treatment guidelines for GED in the medical literature are endoscopic mucosal resection (EMR) or surgery for high grade dysplasia (HGD) and annual endoscopic surveillance with biopsy for low grade dysplasia (LGD) The aim of this study was to determine the treatment plan for GED that is diagnosed by endoscopic biopsy. Materials and Methods: We enrolled 148 patients who were treated by endoscopic mucosal resection (EMR) or endoscopiccsubmucosal dissection (ESD) for GED: there were 63 patients with HGD and 85 patients with LGD and all of them were diagnosed by endoscopic biopsy from January 2006 to December 2008. The results of the final histopathologic reports after EMR or ESD were compared with the results of the endoscopic biopsies. Results: The final histopathologic results of the 148 patients with GED showed 49 (33.1%) patients with adenocarcinoma, 40 (27.0%) patients with HGD and 59 (39.9%) patients with LGD. Among the 63 patients with HGD, 34 (54.0%) patients had adenocarcinoma, 20 (31.7%) patients had HGD and 9 (14.3%) patients had LGD. For the 85 patients with LGD, 15 (17.6%) patients had adenocarcinoma, 20 (23.5%) patients had HGD and 50 (58.8%) patients had LGD Conclusion: Complete resection, including EMR or ESD, is needed for patients with GED diagnosed by endoscopic biopsy and they have HGD. For patients with LGD, EMR or ESD may be needed in addition to endoscopic surveillance with biopsy for making the correct diagnosis and proper treatment because of the possibility of adenocarcinoma.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.4
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• pp.697-702
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• 2001

This study was done to investigate effects of Korean mistletoe extract and lectin on serum GOT, GPT and $\alpha$-L-fucosidase activities and the preneoplastic lesion in chemically induced rat hepatocarcinogenesis. To attain the above objectives weanling Sprangue-Dawley male rats were fed modified AIN-76 diets containing 10% corn oil for 9 weeks. One week after feeding rats were intraperitonealy injected twice with a dose of diethylnitrosamine (DEN, 50 mg/kg body weight(BW)) and were provided 0.05% phenobarbita (PB) with drinking water from one week after DEN treatment until the end of experiment. For the same period as PB treatment, rats were injected mistletoe extract (10 $\mu\textrm{g}$/kg BW European mistletoe, 10 $\mu\textrm{g}$/kg BW and 100 $\mu\textrm{g}$/kg BW Korean mistletoe) and lectin(1 ng/kg BW, 10 ng/kg BW) twice a week. At the end of 9th week rats were sacrificed and the formation of hepatic glutthione S-transferase placental form positive (GST-P+) foci serum GOT, GPT and $\alpha$-L-fucosidase activities were determined. By treatment of mistletoe extract or lectin there were no significant effects on serum GOP, GPT and $\alpha$-L-fucosidase activities whereas those activities showed a tendency to increase by DEN treatment. The formation of GST-P+ foci was significantly decreased by mistletoe extract or lectin treatment especially in group of 100$\mu\textrm{g}$/kg BW Korean mistletoe. These results suggest that Korean mistletoe extract and lectin have a possibility to inhibit hepatocarcinogenesis of animals.