• BMB Reports
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• v.35 no.6
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• pp.615-622
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• 2002

The purpose of this study was to determine the effects of dietary garlic powder on diethylnitrosamine (DEN)-induced hepatocarcinogenesis and cytochrome P450 (CYP) enzymes in weaning male Sprague-Dawley rats by using the medium-term bioassay system of Ito et al. The rats were fed diets that contained 0, 0.5, 2.0 or 5.0% garlic powder for 8 weeks, beginning the diets with the intraperitoneal (i.p.) injection of DEN. The areas of placental glutathione S-transferase (GST-P) positive foci, an effective marker for DEN-initiated lesions, were significantly decreased in the rats that were fed garlic-powder diets; the numbers were significantly decreased only in the 2.0 and 5.0% garlic-powder diets. The p-nitrophenol hydroxylase (PNPH) activities and protein levels of CYP 2E1 in the hepatic microsomes of the rats that were fed the 2.0 and 5.0% garlic powder diet were much lower than those of the basal-diet groups. Pentoxyresorufin O-dealkylase (PROD) activity and CYP 2B1 protein level were not influenced by the garlic-powder diets and carcinogen treatment. Therefore, the suppression of CYP 2E1 by garlic in the diet might influence the formation of preneoplastic foci during hepatocarcinogenesis in rats that are initiated with DEN.

• Toxicological Research
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• v.8 no.1
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• pp.131-137
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• 1992

Sprague-Dawley rats aged six weeks divided into four groups and group 1, 2, 3 and 4 of rats were given an intrapertioneal injection of diethylnitrosamine at 200 mg/kg body weight. Group 4 was Control. Two weeks after beginning of the experiment, group 1 of rats were begun to feed on water containing 0.05% phenobarbital sodium as a promoter for six weeks, and CP-2 were intrapertioneally given to rats of group 2(20mg/kg) and group 3(1mg/kg). Three weeks after beginning of the experiment, partial hepatectomy was performed in all rats. Preneoplastic foci were identified histopathologically by glutathione S-transferase placental form (GST-P) activity. In the Immunohistochemical quantitative analysis of carcinogen-induced foci, it was concluded that CP-2 was not carcinogen.

• 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)

• Toxicological Research
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• v.14 no.3
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• pp.285-291
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• 1998

This study was designed to examine the effects of polyundaturated fatty acid(PUFA) from different sourecs on hepatic lipogenic enzyme and peroxisomal ${\beta}$-oxidation in murine hepatocarcinogenesis initiated by diethylnitrodamine (DEN). Male Sprague-Dawley rats were fed one of three diets containing 10%(w/w)fat; fish oil-corn oil blended(FO), corn oil-beef tallow-fish oil blended(CF), or corn oil-beef tallow-perilla oil blended (CP), from the gestation period. At 10 weeks, animals were received a single inraperitoneal injection of DEN (200mg/kg body weight), were subjected to two-thirds partial hepatectomy 3 weeks later and were sacrificed 8 weeks after DEN initiation. The areas of placental glutathione S-transferase (GST-P) positive foci were significantly smaller in rats fed fish oil containing diets (FO and CF) than those fed CP diet. Fish oil feeding significantly decreased th activities of lipogenic enzyme. Rats fed fish oil containing diets (FO, CF) exhibited the lower fatty acid synthase (FAS) activity than those fed CP diet and FAS activity was positively correlated with areas of GSP-P positivie foci. Glucose-6-phophate dehydrogenase activity was the lowest and peroxisomal ${\beta}$-oxidation was stimulated in rats fed FO diet compared to other groups. It was also found that serum cholesterol was decreased in FO group. Therefore, the preventive effect against hepatocarcinogenesis and hypolipidemic effect of fish oil can be explained partly by suppression of the hepatic lipogenesis and by increase of peroxisomal ${\beta}$-oxidation.

• 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.

• Korean Journal of Veterinary Research
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• v.34 no.3
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• pp.609-617
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• 1994

This study was performed for assessing carcinogenicity of Folpet using medium-term carcinogenicity bioassay. Sprague-Dawley rats aged six weeks divided into four grout's and were initially given an intraperitoneal injection of diethylnirosamine at 200mg/kg body weight. Two weeks later, group 1(negative control) was treated with basal diet. A Folpet was given per oral administration to group 2(100 ppm) and goup 3(1,000 ppm). Group 4 was fed on water containing 0.05% phenobarbital sodium as a promtor for six weeks. At three weeks after beginning of the experiment, partial hepatectomy was performed in all rats. The tumor-promoting effects were examined by the numbers and areas per $cm^2$ of induced glutathion S-tranferase placetal form(GST-P) positive foci in liver, and silver stained nucleolar organizer regions(AgNORs) which have recently introduced as one of the indicators for the cell proliferative activity. As the results, Folpet didn't have tumor-promoting effects on GST-P positive foci developement and AgNORs during promoting stage after initiation, whereas phenobarbital sodium treatment group showed promoting effect. It was concluded that Folpet didn't have promoting effect at 500, 1,000 ppm using this midium-term carcinogenicity bioassay model.

• Environmental Analysis Health and Toxicology
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• v.13 no.3_4
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• pp.71-75
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• 1998

Carbendazim, which is widely used fungicide, was investigated for rat hepatocarcinogenesis using a medium-term carcinogenicity bioassay. All rats were initially given a single dose (200mg/kg) of diethylnitrosamine (DEN) i.p. and then, starting 2 weeks later, carbendazim treatment group and positive control group received carbendazim (7 mg/kg/ day) and 2-acetylaminofluorene (2-AAF, 1%), respectively, in the diet for 6 weeks. All rats were subjected to two-thirds partial hepatectomy (PH) at week 3 and sacrificed at week 8. Carcinogenic potential was scored by comparing the number and area per cm$^2$ of induced glutathione-S-transferase placental form (GST-P) positive foci in the liver. Carbendazim had no effect in the increase of body weight, hematological and biochemical values, and the number and area of GST-P positive loci. These results suggest that this bioassay using DEN-PH method can be useful for detection of hepatocarcinogenic potentials of pesticide.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.339-339
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• 1994

It has been reported that Indole-3-carbinol (I3C), a naturally occurring compound In cruclferous vegetables, exerts anticarcinogenic activity In several organs In rodents. The modifying effects of I3C were therefore assessed uging a rat multi-organ carcinogenesis model. A total of 100 male Sprague-Dawley rats were divided Into 3 groups. Animals of groups 1 and 2 were sequentially treated with diethylnitrosamine (DEN; 100 mg/kg b.w., i.p.), N-methylnitrosourea (NNU; 20 mg/kg b.w., 4 times for 2 weeks, i.p), and dihydroxy-di-N-propylnitrosauine (DHPN; 0.1% In d.w. for 2 weeks) for 4 weeks (DMD treatment). Animals of groups 1 and 3 were given the diet of 0.25% I3C for 20 weeks after DMD initiation and then were given basal diet for 28 weeks. All animals were sacrificed at week 24 and 52, respectively. I3C has been clearly demonstrated promoting effects on the development of glutathione S-transferase placental form (GST-P) positive hepatic foci at 24 weeks of the experiment. And I3C also exerted promoting potential In the hepatocellular adenoma (4/14; 29%) and the adenoma (7/14; 50%) of the thyroid gland at 52 weeks of the experiment. Therefore, I3C may promote hepatocarcinogenesis and thyroid tumorigenesis in the rat multi-organ carcinogenesis model.

• Korean Journal of Veterinary Research
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• v.32 no.4
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• pp.649-661
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• 1992

This study was performed to compare DNA content by flow cytometer (FCM) and glutathione S-transferase placental form (GST-P) positive foci for searching objective and accurated properties of tumor. Sprague-Dawley rats aged six weeks were divided into three groups and group 1 and 2 of rats were given an intraperitoneal injection of diethylnitrosamine at 200mg/kg body weight and group 3 of rats were given saline. Three weeks after beginning of the experiment, all groups were performed partial hepatectomy. Group 1 of rats were begun to feed on diets containing 0.02% 2-acetylaminofluorene as a promoter for six weeks, group 2 and 3 of rats were begun to feed on basal diets. At 4, 6, and 8 weeks after initiation, all groups of rats were killed, livers were extracted for H & E stain, immunohistochemical stain, and DNA ploidy analysis. In quantitative analysis for GST-P positive lesion number and area by using Image Analyzer, group 1 and 2 represented significant difference in comparison with group 3. In ploidy distribution, diploid cells of group 1 and 2 were increased significantly in comparison with those of group 3 at 4, 6, and 8 weeks after initiation, respectively tetraploid cells were reduced. But S-phase cells were not changed significantly. It is concluded that ploidy change by FCM is useful as objective data for early detection in hepatocarcinogenesis. Therefore, methodology and study of DNA content are carried out for more objective and accurate ploidy analysis in liver tumor.

• 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.