• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2825-2830
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• 2014

Purpose: To study the effect of Cleistocalyx nervosum extract (CE) on diethylnitrosamine (DEN) and phenobarbital (PB) induced oxidative stress in early stages of rat hepatocarcinogenesis. Materials and Methods: Male Wistar rats were divided into 4 groups, with Group 1 as a negative control and Group 2 was a positive control receiving DEN injections once a week and PB in drinking water for 6 weeks. Two weeks before DEN initiation and PB treatment, Groups 3 and 4, were fed with 500 and 1000 mg/kg of CEs, respectively, for 8 weeks. Results: A number of GST-P-positive foci, preneoplastic lesions, in the liver were markedly increased in carcinogen administered rats, but was comparatively decreased in rats treated with 1000 mg/kg of CE. The CE reduced malondialdehyde in serum and in the livers of rats treated with DEN and PB. Moreover, CE significantly increased the activities of glutathione peroxidase and catalase in rat liver. Conclusions: CE appeared to exert its chemopreventive effects by modulating antioxidant status during DEN and PB induced early stages of hepatocarcinogenesis in rats.

• Journal of Nutrition and Health
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• v.33 no.1
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• pp.23-32
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• 2000

The purpose of this study was to investigate the effcts of n-3, n-6 fatty arid and d-limonene on histopathological and biochemical changes in experimental rat hepatocarcinogenesis. To attain the above objectives, weanling Sprague-Dawley female rats were intraperitoneally injected twice with a dose of diethylnitrosamine(DEN, 50mg/kg body weight) and after 1 week 0.05% phenobarbital was provided with water. Sardine oil rich in n-3 fatty acids and corn oil rich in n-6 fatty acids were fed at 15% by weight and 5% d-limonene was added to the diet in each group. Ten weeks or 20 weeks after DEN treatment, rats were sacrifirced. The formation of glutathione S-transferase placental form positive(GST-P$\^$+/) foci was significantly decreased by the treatment of either sardine oil or d-limonene HMG-CoA reductase activity was not affected by dietary oils and d-limonene. Protein kinase C (PKC) activity was decreased by either sardine oil or d-limonene. Particularly d-limonene decreased the membrane PKC activity. Membrane Cholesterol/Phospholipid(Chol/PL) ratio was significantly decreased by d-limonene in sardine oil group. The data showed that GST-P$\^$+/ foci number was positively correlated with membrane PKC activity and serum cholesterol and negatively correlated with liver cholesterol level. These results suggest informations about the correlation between histopathological and biochemical changes such as cholesterol metabolism and PKC activity in experimental hepatocarcinogenesis and thereby can elucidate the possible mechanism related to the cancer inhibition.(Korean J Nutrition 33(1) : 23-32, 2000)

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.103-104
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• 2003

The incidence of liver cancer is markedly sex-differentiated epidemiologically, with a much higher frequency in men than in women. In experimental animals, male have higher incidence of liver tumors than female in carcinogen-induced tumors as well as spontaneous ones. Our studies were investigated to examine the modifying effects of sex hormones in the proneoplastic lesions of liver on diethylnitrosamine (DEN) - induced hepatocarcinogenesis. (omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.103-108
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• 2015

Curcumin is widely used as a traditional medicine. This work was aimed to investigate its possible protective effect against chemically induced hepatocellular carcinoma (HCC) in rats. Fifty male albino rats were divided into five groups (n=10, each). The control group received a single dose of normal saline, the diethylnitrosamine (DENA) group received a single intra-peritoneal dose at 200mg/kg body weight, and the 3rd, 4th and 5th groups were given DENA and daily administrated curcunine (CUR) via intra-gastric intubation in doses of 300, 200 and 100 mg/kg b.wt. respectively for 20 weeks. Serum, and liver samples were used for determination of alpha feto-protein (AFP), interleukin-2 (IL-2), interleukine-6 (IL-6), serum liver enzymes (AST, ALT, ALP and GGT) levels as well the activities and gene expression of glutathione peroxidise (GPx), glutathione reductase (GR), catalase (CAT) and super oxide dismutase (SOD). Curcumin significantly lowered the serum levels of AFP, IL-2 and IL-6, ALT, ALT, and malondialdehyde (MDA) as well gene expression of IL-2 and IL-6. In contrast it increased the gene expression and activities of Gpx, GRD, CAT and SOD. The protective effect of CUR against DEN-induced hepatocarcinogenesis in albino rats was proven.

• Korean Journal of Veterinary Service
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• v.22 no.1
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• pp.61-70
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• 1999

This study is concerned with assessment of diethylnitrosamine(DEN) induced liver cell carcinogenesis by measurement of changes preceding the development of neoplasms. Therefore, it was undertaken to investigate the changes of liver-specific enzyme activities in rats (Sprague-Dawley) by ad libitum feeding of DEN. And also, as another objective index in urine, the level of urinary biopterin was measured by high performance liquid chromatography(HPLC) method. The results were as follows ; 1. Minor behavioral change, brittleness of hair and decreased amount of water and diet intake were observed in rats 7 weeks after DEN administration. 2. The body and liver weights were significantly(p<0.05) decreased in rats 11 weeks after DEN administration. 3. The ratio of liver weight to body weight was rather stable and not significantly decreased in the all treatment groups. 4. The liver specific enzyme activities(AST, ALT,$\gamma$-GTP) were significantly(p<0.05) increased in all treatment groups compared to control group. 5. Compared to normal level, urine biopterin level was significantly (p<0.05) increased in all treatment groups(p<0.05). In conclusion, this result confirmed that the DEN was one of the potent hepatocarcinogens. In experimental model of rats exposed to DEN, the results indicated that values of liver specific enzyme activities(AST, ALT, $\gamma$-GTP) and urine biopterin level could be useful complementary tumor indices.

• The Korean Journal of Food And Nutrition
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• v.23 no.2
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• pp.276-284
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• 2010

The effects of different dietary fatty acids on the hepatic glutathione S-transferase(GST-P) positive foci and glutathione related enzyme system were investigated in carcinogen treated rats. Weaning male Sprague Dawley rats were divided into three groups and fed the diets of 15% corn(CO), perilla(PO), and sardine oil(SO), respectively. Hepatocellular carcinogenesis was initiated with diethylnitrosamine(DEN) and then fed the diet containing 0.02% 2-acetylaminofluorene(2-AAF) followed by 0.05% phenobarbital for 10 weeks. The hepatic tissues were homogenized and centrifugated to prepare microsomal and cytosolic fractions. The enzyme activities of hepatic glutathione S-transferase(GST), glutathione reductase(GR), and glutathione peroxidase(GPx) were determined from cytosolic fractions. The number of GST-P hyperplastic nodules was the highest in corn oil group at 6th week, the early stage of hyperplastic nodule formation. GST activities were increased significantly by carcinogens in all dietary groups after 6th wk. GR activities followed the same trend as GST activities. GPx activities were decreased by carcinogens in all dietary groups at 10th week. In this experiment, corn oil diet may have promotive effect on hyperplastic nodule formation during the early promotional stages of chemical carcinogenesis.

• Preventive Nutrition and Food Science
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• v.8 no.2
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• pp.158-161
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• 2003

This study investigated the effects of a ${\gamma}$-irradiated pork (0-30 kGy) diet on lipid peroxidation, cytochrome P-450 content, microsomal glucose 6-phosphatase (G-6-Pase) activity and antioxidative defense systems in diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis. The body weight of rats fed irradiated diets did not change significantly. Liver weight was significantly increased by the administration of DEN, but not by irradiated diets at any dose level. There were no significant effects of gamma irradiation on the content of microsomal malondialdehyde (MDA), cytochrome P-450, or on the activity of G-6-Pase. However, with DEN treatment, cytochrome P-450 content was significantly increased while microsomal G-6-Pase activity was significantly decreased. The ${\gamma}$-irradiated diet supplement did not affect serum retinol or $\alpha$-tocopherol concentrations. However, it did cause a significant decrease in hepatic retinol at 30 kGy. With DEN treatment, hepatic retinol content was even more significantly (p<0.05) decreased compared to the non-irradiated control. The enzyme activities related to antioxidative defense systems, including glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rx) and glutathione S-transferase (GST) were not affected by gamma irradiation. Those results suggest that an irradiated pork diet up to 30 kGy may not cause a health hazard in experimental animals.

• BMB Reports
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• v.28 no.6
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• pp.504-508
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• 1995

The electrophoretic patterns of plasma membrane surface proteins of normal rat liver cells and rat hepatomas were compared in 10% non-denaturing and 7-15% gradient non-denaturing gel. Chemical carcinogens, 2-Me DAB (2-methyl-4-dimethylaminoazobenzene) and DENA (diethylnitrosamine), were used to induce hepatoma in rats. One protein which disappeared in hepatoma was identified in normal rat liver by non-denaturing gel electrophoresis. Rabbit antisera were raised against this specific protein, and the protein was purified by Sephacryl S-200 column and immunoaffinity chromatography using the purified antibody. The purified protein showed two bands of molecular weights approximately 50 $kD_{\alpha}$ and 52 $kD_{\alpha}$ by SDS-polyacrylamide gel electrophoresis, which reacted specifically with the antibody. However only one band was observed in non-denaturing gel and also in isoelectric focusing with a pI value of 6.6. This study showed the existence of an unique protein on the plasma membrane surface of normal rat liver cells which disappeared in rat hepatomas induced by chemical carcinogens.

• Preventive Nutrition and Food Science
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• v.1 no.2
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• pp.214-219
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• 1996

This study was done to investigate effects of n-s fatty acids and vitamin E supplement on the preneoplastic hepatic enzyme altered foci and cholesterol metabolism in experimental hepatocarcinogenesis system. Weaning male Sprague-Dawley rats were fed the diet containing either 15% corn oil(CO) or sardine oil(SO) with or without vitamin E 800IU supplementation for 12 weeks. After two weeks of feeding, rats were intraper-itoneally injected with a single dose of diethylnitrosamine(DEN:200mg/kg, BW). At the 4th week, rats were given the diet containing 0.02% acetylaminofluorene(AAF) for next 4 weeks. At the 6th Week, 0.05% pheno-barbital was incorporated into diet for 6 weeks. At the end of 12th week, rats were sacrificed and hepatic glutathions S-transferase placental form positive(GST_{TEX}$P^{+}${/TEX}) foci and serum and liver cholesterol levels were determined. GST_{TEX}$P^{+}${/TEX} formation was significantly decreased by SO feeding when compared with Co feeding but it tended to be enhanced by vitamin E supplementation. Histopathological changes were similar to patterns of GST_{TEX}$P^{+}${/TEX} formation in almost all dietary groups. Serum and hepatic cholesterol levels of SO fed groups were significantly lower than those of CO fed groups. Carcinogen treatments significantly increased serum and liver cholesterol levels in CO fed groups but not in SO fed groups. Correlation data showed a positive correlation(${\gamma}$=0.83, p<0.01) between serum cholesterol level GST_{TEX}$P^{+}${/TEX} foci area. These results indicate that sardine oil as a m-3 fatty acid source may have a reducing effect in rat hepatocarcinogenesis by the altheration of cholesterol metabolism.

• Toxicological Research
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• v.13 no.1_2
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• pp.23-27
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• 1997

This study was performed to examine the anti-cancer effect of Red Ginseng in the DENGalN-PH-induced hepatic tumor model system in rats. One hundred of male SPF Sprague-Dawley rats(6weeks old) were randomly divided into five groups. Rats in groups 1, 2, 3, and 4 were administered to diethylnitrosamine intraperitoneally 200 mg/kg body weight for the caner initiation. Rats in group 5 were given to saline as a control. On two weeks after cancer initiation, rats in groups 1 and 3 were fed on diet containing 0.01% of acethylaminofiuorene(AAF) which is strong cancer-promotor for 6 weeks, while rats in groups 2 and 4 were fed on water containing 0.05% of phenobarbital which is weak cancer.promotor for 6 weeks. Rats in groups 1 and 2 were treated with diet containing 3% of Red Ginseng for six weeks(from 9th week till 15th week after cancer initiation). Rats in all groups were necropsied time-sequencially at 8, 15, and 36 weeks. The hepatic lesions of rat treated with carcinogens expressed glutathione S-transferase placental form(GST-P) at 8 week. The GST-P positive foci of rats treated with AAF were larger than that of any other rats, while the GST-P positive foci of rats treated with AAF and red ginseng were significantly decreased. This anti-cancer effect of Red ginseng might be involved in the enhacement of natural killer cell activity. To know whether there is direct relationship between Red Ginseng and natural killer cell activity, the activity of natural killer cell was examined after treatment AAF, AAF+Red ginseng and Red ginseng only, respectively. Comparing with natural killer cell activity in AAF-treated group, natural killer cell activity was significantly activated in AAF+ Red ginseng-treated group. This indicated that Red ginseng might enhance natural killer activity after treatment carcinogen in rats. These results suggested that Red ginseng might have a cancer prevention ability by promoting natural killer cell activity during hepatocarclnogenesis.