• Korean Journal of Veterinary Research
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• v.29 no.1
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• pp.45-50
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• 1989

홍삼 및 수삼이 랫트의 간조직에서 diethylnitrosamine(DEN)에 의해 유도되는 preneoplastic altered foci 형성에 미치는 영향을 관찰한 바 다음과 같은 결과를 얻었다. Altered foci의 지표로 사용되는 glutathione S-transferase (GST-P)-positive foci의 숫자는 DEN 단독투여군($9.07{\pm}5.69$)에 비하여 수삼병행 투여군 ($4.77{\pm}3.23$)에서, 면적은 DEN 단독투여군($0.93{\pm}0.65$)에 비하여 홍삼병행투여군 ($0.50{\pm}0.31$)에서 각각 현저한 감소를 나타냈다. 이러한 결과는 홍삼 및 수삼이 간암 발생을 억제하는 작용이 있음을 암시하였다.

• Korean Journal of Veterinary Research
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• v.32 no.4
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• pp.629-633
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• 1992

Caffeine이 랫드의 간조직에서 diethylnitrosamine(200mg/kg B.W., DEN)에 의해 유도되는 preneoplastic altered foci형성의 promotion단계에 미치는 효과를 관찰한 바 다음과 같은 결과를 얻었다. Altered foci의 지표로 사용되는 glutathione S-transferase(GST-P)-positive foci의 수는 caffeine 음수 $m{\ell}$당 2mg 병행투여군($3.10{\pm}2.74$) 및 1mg병행 투여군($5.86{\pm}2.83$) 모두에서 DEN 단독투여 대조군($11.55{\pm}5.82$)에 비하여 현저히 낮게 나타났으며 면적 또한 caffeine 2mg 병행투여군($0.13{\pm}0.11$), 1mg 병행투여군($0.21{\pm}0.12$)에서 DEN 단독투여 대조군($0.76{\pm}0.33$)에 비하여 유의성있는 낮은 수치가 관찰되었다. 간 세포배양에서 unscheduled DNA synthesis(UDS)는 DEN($250{\mu}g/m{\ell}$ of medium)단독처리군에 비하여 caffeine($200{\mu}g/m{\ell}$ of medium) 처리시 약 70% 감소하였다. 이러한 결과는 caffeine이 간암발생의 promotion단계에 작용하여 억제효과를 나타냄을 암시하며 이는 DNA회복의 억제와 관계됨을 알 수 있었다.

• Korean Journal of Veterinary Research
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• v.31 no.3
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• pp.337-342
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• 1991

Caffeine이 랫트의 간조직에서 diethylnitrosamine(200mg/kg B.W., DEN)에 의해 유도되는 preneoplastic altered foci형성의 initiation단계에 미치는 효과를 관찰한 바 다음과 같은 결과를 얻었다. Altered foci의 지표로 사용되는 glutathione S-transferase(GST-P)-positive foci의 수는 caffeine 음수수 ml 당 2mg병행투여군 $(7.48{\pm}3.33)$ 및 1mg 병행 투여군 $(7.50{\pm}3.32)$ 모두에서 DEN 단독투여대조군$(14.08{\pm}5.16)$에 비하여 현저히 낮게 나타났으며, 면적 또한 caffeine 2mg병행투여군 $(0.29{\pm}0.17)$, 1mg병행투여군 $(0.30{\pm}0.13)$에서 DEN단독투여대조군 $(0.46{\pm}0.21)$에 비하여 유의성 있는 낮은 수치가 관찰되었다. 이러한 결과는 caffeine이 간암발생의 initiation 단계에 작용하여 억제효과를 나타냄을 암시하였다.

• 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.

• Korean Journal of Veterinary Service
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• v.22 no.2
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• pp.135-149
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• 1999

This study was concerned with assessment of dietynitrosamine (DEN) induced liver cell carcinogenesis by measurement of changes preceding the development of neoplasms. The changes of hepatic morphology in rats(Sprague-Dawley) were detected by hematoxylin-eosin stain and immunohistochemistry(PCNA). 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. Variable size of liver tumor and hepatomegaly were observed in rats treated with DEN after 10 weeks. 3. Numerous vacuoles were showed on the midzonal and or peripheral areas of hepatic lobules. The large and polymorphological hepatocytes with eosinophilic cytoplasm or densely basophilic mitotic nucleoli were showed. 4. Several proliferative small round cells were shown on vacuolated and necrotic areas in peripheral hepatic lobules or portal areas. 5. PCNA-positive cells were showed on the vacuolated portal areas and peripheral areas of hepatic lobules. Maximal positivity was 23.6% in the areas of small round cells. In conclusion, this result confirmed that the DEN was one of the potent hepatocarcinogens. In histopathological analysis, the altered foci, hyperplastic nodules, neoplastic nodules, adenomas and carcinomas were observed in liver tumors induced by administration of DEN in rats.

• Journal of Veterinary Clinics
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• v.16 no.1
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• pp.108-117
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• 1999

Hepatic tumorigenesis was induced by ad libitum feeding of diethylnitrosamine (DEN) only. We could also observe hepatic tumor induction in 100% of DEN treated rats without any other cocarcinogen. The liver specific enzyme activities (AST, ALT, ALP, ${\gamma}$-GTP) were significantly increased (P<0.05) in all treated groups compared to control and induced apoptosis groups. In histopathological analysis, the altered foci, hyperplastic nodules, neoplastic nodules, adenomas and carcinomas were observed in liver tumors induced by administration of DEN in rats. Lipopolysaccharide-induced apoptosis in D-galactosamine sensitized mice was investigated in hepatocytes in vivo. Typical morphological changes of apoptosis were detectable in liver 12 hr and 24 hr after the injection of Lipopolysaccharide (5 $\mu\textrm{g}$) and D-galactosamine (20 mg) to mice. It was suggested that organ specific enzyme activities and morphological findings might be very useful for understanding the role of hepatic tumorigenesis including the apoptotic cell death.

• Nutrition Research and Practice
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• v.2 no.2
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• pp.80-84
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• 2008

Beneficial effects of dehydroepiandrosterone (DHEA) supplement on age-associated chronic diseases such as cancer, cardiovascular disease, insulin resistance and diabetes, have been reported. However, its mechanism of action in hepatocellular carcinoma in vivo has not been investigated in detail. We have previously shown that during hepatocellular carcinogenesis, DHEA treatment decreases formation of preneoplastic glutathione S-transferase placental form-positive foci in the liver and has antioxidant effects. Here we aimed to determine the mechanism of actions of DHEA, in comparison to vitamin E, in a chemically-induced hepatocellular carcinoma model in rats. Sprague-Dawley rats were administered with control diet without a carcinogen, diets with 1.5% vitamin E, 0.5% DHEA and both of the compounds with a carcinogen for 6 weeks. The doses were previously reported to have anti-cancer effects in animals without known toxicities. With DHEA treatment, cytosolic malate dehydrogenase activities were significantly increased by ${\sim}5$ fold and glucose 6-phosphate dehydrogenase activities were decreased by ${\sim}25%$ compared to carcinogen treated group. Activities of Se-glutathione peroxidase in the cytotol was decreased siguificantly with DHEA treatment, confirming its antioxidative effect. However, liver microsomal cytochrome P-450 content and NADPH-dependent cytochrome P-450 reductase activities were not altered with DHEA treatment. Vitamin E treatment decreased cytosolic Se-glutathione peroxidase activities in accordance with our previous reports. However, vitamin E did not alter glucose 6-phosphate dehydrogenase or malate dehydrogenase activities. Our results suggest that DHEA may have decreased tumor nodule formation and reduced lipid peroxidation as previously reported, possibly by increasing the production of NADPH, a reducing equivalent for NADPH-dependent antioxidant enzymes. DHEA treatment tended to reduce glucose 6-phosphate dehydrogenase activities, which may have resulted in limited supply for de novo synthesis of DNA via inhibiting the hexose monophophaste pathway. Although both DHEA and vitamin E effectively reduced preneoplastic foci in this model, they seemed to fimction in different mechanisms. In conclusion, DHEA may be used to reduce hepatocellular carcinoma growth by targeting NADPH synthesis, cell proliferation and anti-oxidant enzyme activities during tumor growth.

• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.545-552
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• 2017

Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett's test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in $C_{max}$, and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in $C_{max}$ and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.