• Toxicological Research
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• 제27권4호
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• pp.247-251
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• 2011

To clarify whether inhibitory effect of estrogen on liver tumor is associated with cell proliferation, we investigated its role in diethylnitrosamine (DEN)-induced rat preneoplastic lesions, with time sequenced manners. F344 male rats (n = 90) were divided into three groups at 5 weeks of age. The mini-osmotic pumps providing a continuous infusion of DEN was implanted into the abdominal cavity of each animal in group 1, 2 and 3 at 6 weeks of age. To see the effect of estrogen, pellet containing 1 or 10 ${\mu}g$ of estradiol-3-benzoate (EB) was implanted subcutaneously in the animals of groups 2 or 3, respectively, one week prior to DEN treatment. Ten animals of each group were euthanized at 10, 14 and 18 weeks after DEN treatment. Liver tissues at each time point were fixed in 10% phosphate-buffered formalin and were processed and embedded in paraffin and 5 ${\mu}g$ sections mounted on a silanized slide. Glutathione S-transferase placental form (GST-P) positive foci and 5-bromo-2-deoxyuridine (BrdU) labeling cells were detected at each time point. Area of GST-P positive foci in DEN+EB 1 or 10 ${\mu}g$ group was significantly decreased compared to DEN alone at 14 weeks (p < 0.01 or p < 0.05, respectively) an at 18 weeks (p < 0.05 or p < 0.01, respectively). BrdU index in DEN+EB 1 or 10 ${\mu}g$ groups was significantly decreased compared to DEN alone at 14 weeks and at 18 weeks (p < 0.01). Taken together, we conclude that EB treatment decrease the DEN-induced liver preneoplastic lesions and this may be associated with decrease of cellular proliferation.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1611-1616
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• 2014

Spirogyra neglecta, a freshwater green alga, is a local food in the northern and northeastern parts of Thailand. This investigation explored the anticarcinogenicity of S neglecta and its possible cancer chemopreventive mechanisms in rats divided into 14 groups. Groups 1 and 10 served as positive and negative control groups, respectively. Groups 1-9 were intraperitoneally injected with diethylnitrosamine (DEN) once a week for 3 weeks. Groups 10-14 received normal saline instead. One week after the last DEN injection, groups 2-5 were administered for 9 consecutive weeks various doses of S neglecta extract (SNE) and dried S neglecta (SND), mixed with basal diet. Groups 6-9 and 11-14 similarly were administered various doses of SNE and SND starting from the first week of the experiment. Administration of SNE and SND was not associated with formation of glutathione-Stransferase placental form (GST-P) positive foci in rat liver. SNE and SND during initiation phase significantly reduced the number of GST-P positive foci in rats injected with DEN. The number of GST-P also diminished in groups treated with SNE and SND after injection with DEN, except for the low dose extract group. SNE showed stronger anticarcinogenic potency than SND. Furthermore, SNE also decreased the number of Ki-67 positive cells. However, the numbers of TUNEL-positive cells in the liver of the SNE-treated groups were not statistically different from the controls. The GST activity in 50 mg/kg bw of SNE and 1% of SND groups was significantly increased as compared to the positive control. In conclusion, Spirogyra neglecta (Hassall) K$\ddot{u}$tzing showed cancer chemopreventive properties at the early stages of diethylnitrosamine-induced hepatocarcinogenesis in rats. Possible inhibitory mechanisms include enhancement of the activities of some detoxifying enzymes and/or suppression of precancerous cells.

• 대한지역사회영양학회지
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• 제2권5호
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• pp.735-744
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• 1997

The effect of green tea drinking on the hepatocellular chemical cacinogenesis have been studied. Placental glutathione S-transferase(GST-P) positive foci area in a liver tissue, contents of thiobarbituric acid reactive substances(TBARS), total cytochrome P450 and glucose 6-phospphatase(G6P) activity in hepatic microsomes were investigated. Weaning Sprague-Dawley male rats were fed AIN-76A diet with deionized water or green tea infusion, Rats of CTR and CTR+ groups were provided deionized water while GTI and GTI+ groups were provided green tea instead of deionized water for the entire experimental period of 13weeks. Rats of GTP and GTP + groups had deionized water for the first 6 weeks and switched to green tea for the last 7weeks of the experimental period. CTR+, GTI +, and GTP + groups were carcinogen treated groups, Diethylnitrosamine(DEN) was injected as a single dose of 200mg/kg body weight intraperitoneally after 4 weeks of feeding. 2-Acetyla-minofluorene(AAF) was used as a carcinogen proliferater and suppled in the diets of carcinogen treated rats as 0.02% content for the last 6weeks starting from 2weeks after DEN injection. Rats were sacrificed after 13week weeks of feeding. The area and number of GST-P positive foci detected in carcinogen treated rats were decreased by green tea ingestion but when timing and duration of green tea ingestion was delayed after promotion period as in GTP + group, GST-P positive foci were not decreased as much as in GTI+ group. TBARS contents of carcinogen treated rats decreased by 13weeks of green tea ingestion but GTP groups did not show statiscally significant differences. G6P activities tended to decrease by carcinogen treatment but changes were not statiscally significant by green tea ingestion. Total cytochrome P450 contents were increased by carcinogen treatment. Thirteen weeks of green tea ingestion (GTI) also increased to total cytochrome P450 contents while 7weeks of green tea ingestion(GTP) did show any effects. These results suggest that green tea has suppressive effects on hepatocellular chemical carcinogenesis probably through the activities of antioxidant compounds. (Korean J Community utrition 2(5) : 735∼744, 1997)

• 대한수의학회지
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• 제29권1호
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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.

• 한국수의병리학회지
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• 제1권1호
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• pp.33-39
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• 1997

We investigated metabolism and carcinogenesis in livers of Sprague-Dawley rats fed juices and pelleted diets containing Korean native plants petasites japonicus Maxim by evaluating cell localization and expression of cytochrome P450s and GST-P. Anti-cytochrome P450s application in liver sections revealed three to four times increased expression of cytochrome P450E1 immunoreactivity in degenerative hepatocytes when compared to histologically normal hepatocytes. Anti-GST-P in showed positive pren plastic foci as well as in individual hepatocytes randomly scattered throughout all liver sections examined. Additionally GST-P was evident in proliferative endothelial cells and biliary epithelial cells in exposed rat livers. These results suggested that the increased level of cytochrome P4502E1 in affected hepatocytes was a direct consequence of Petasites japonicus toxicity. Further immunoreactivity to anti-GST-P in hepatocytes endothelial cells and biliary epithelial cells indicated a possible preneoplastic effects of Petasites japonicus in Sprague-Dawley rat.

• Environmental Analysis Health and Toxicology
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• 제13권3_4호
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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.

• BMB Reports
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• 제35권6호
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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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• 제14권3호
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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.

• 한국식품위생안전성학회지
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• 제6권1호
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• pp.1-12
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• 1991

생후 6주령된 Fischer344 랫드를 4개군으로 나누어 시험 개시 일에 diethylnitrosamine을 제 1, 2, 3 군에 복강내로 각각 체중 kg당 200mg을 1회 주사하였고, 제 4군에는 생리적 식염수를 복강내로 1회 투여하였으며, 간 변화의 증폭을 위해 시험개시 3주후에 간의 약 67%를 부분절제하였다. 제1,2 군은 시험개시 후 제 2주부터 2-acetylaminofluorene(2-AAF)를 사료에 0.02%가 되게 섞어 4주간 투여하였고, 제3군과 대조군인 제4군에는 기초 사료만을 급여하였다. 제 1,3군은 철저항병소의 검색을 위하여 시험종료 2주전에 iron dextran을 체중 100g당 0.125 mg을 주 3회 피하로 투여하였고, 시험종료 후에 모든 랫드를 부검하여, 고정제로 고정한 후 일반적인 조직표본을 만들었다. 전암병소 검색을 위해 glutathione S-transeferase placental form(GST-P)에 대한 면역조직화화적 염색과 Perl's 법에 의한 철염색을 한 후, 동일한 조직을 연속절편하여 hematoxylin & eosin 염색한 것과 비교하였고, 칼라 화상분석기로 병소의 면적을 계산하여 통계학적 분석을 하였다. 본 연구의 결과는 철 저항 nodule이 주위의 정상조직과 한계가 어느정도 굴별되어 병변을 검색할 수 있었으나 GST-P 양성 nodule에 비하여 확실하지 않았고, 또한 철저항 foci는 주위의 정상조직과 한계가 명확하게 구별할 수 없었다. 간엽 전체에 대한 병소의 면적비교는 철 저항병소의 면적이 GST-P양성 병소의 면적보다 유의성 있게 낮았다. (p<0.01). 따라서 전암병소를 검색하는데는 GST-P양성 병소에 의한 검색이 철 저항 병소에 의한 검색보다 더 민감하고 믿을만한 지표가 되는 것으로 생각된다.하고 있는 각종 지구관측위성(EOS)들이 실용화 될 2000년 대에는 일반 지구환경감시는 물론 수계환경 감시 체계구축에 획기적인 진전이 있을 것으로 기대된다.limon(Jordan et Fowler) 및 청자갈치 Allolepis hollandi Jordan et Hubbs, 장갱이란 Stichaeidae의 세줄베도라치 식nogrammus hewagrammus(Temminck et Schlegel), 장갱이 Stichaeus grigorjemi Her\ulcornerenstein, 왜도라치 Chri'olophis wui(Wang et Wang ) , 괴도라치 Chirolophis joponicus(Jordan et snyder) , 벼슬베도라치 각ectrias benjamini Jordan et Snyder, 가시베도라치 Lumpenella nigricons Matsubara, 육점날개 Ophistocentws zonope jordan et Snyder, 그물베도라치 Dictyosoma burgeri Van der Hoeven 및 황점 베도라치Dictyosoma wbrimaculata Yatsu, Yasuda et Taki, 그리고 황줄베도라치란 Pholididae의 황줄베도라치 Phoris taczanowskii(Steindachner), 오색베도라치 Phoris omotus (Girad), 베도라치 Pholis nebuloso(Temminck et Schlegel), 횐베도라치 Pholisfangi(Wang et Wang) 및 점베도라치 Pholis crossispino(Temminck et Schlegel)의 17속 25종이 분류되었다. 이중에서 Zoarchias glaber, Chirofophis oui, Alectrias benjamini, Dictyosoma mbrimaculamia 및 Pholis crassispina의 5종은

• Toxicological Research
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• 제13권1_2호
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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.