• 한국식품영양과학회지
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• 제28권3호
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• pp.638-645
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• 1999

This study was done to investigate effects of ${\gamma}$ irradiated beef feeding on the formation of gluta thione S transferase placental form positive(GST P+) foci, lipid peroxidation, cytochrome P450 system and microsomal glucose 6 phosphate activity in diethylnitrosamine(DEN) initiated rat hepatocarci nogenesis. Weaning Sprague Dawley male rats were fed the diet containing ${\gamma}$ irradiatied ground beef at the dose of 0, 3, 5kGy as a 20% of protein source for 8 weeks. One week after feeding, rats were intraperitoneally injected twice with a dose of DEN(50mg/kg BW). As a promoter, 0.05% phenobarbital was fed in drinking water from one week after DEN treatment until the end of experiment. At the end of 8th week, rats were sacrificed and hepatic GST P+ foci, microsomal malondialdehyde(MDA) and conjugated diene contents were determined. In addition, cytochrome P450 content and the activities of NADPH cytochrome P450 reductase and glucose 6 phosphatase were also measured. There was no significant effect by gamma irradiation on microsomal MDA content, conjugated diene, cytochrome P450 content and activities of NADPH cytochrome P450 reductase and glucose 6 phosphatase. However with DEN treatment, microsomal MDA content and conjugated diene contents were significantly changed. Cytochrome P450 content was also significantly increased while microsomal glucose 6 phophatase activity was significantly decreased with DEN treatment. However activity of NADPH cytochrome P450 reductase was not affected. An interesting finding in this study was that the number and area of hepatic GST P+ foci of the rats fed gamma irradiated beef were significantly(p<0.05) lower than those of the control. Such a lowering effect on GST P+ foci formation was highest at the dose of 3kGy than others. Overall results suggest that the consumption of low dose of gamma irradiated beef does not affect the formation of lipid peroxide, cytochrome P450 system and membrane stability.

• Toxicological Research
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• 제14권4호
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• pp.475-481
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• 1998

This study was performed to investigate the modifying effect of the general (GPA) and the fermented pilose antler (FPA) on experimental hepatocarcinogenesis and Natural Killer cell activity in rats. Specific pathogen free, 5-week male Sprague-Dawley rats were divided into four groups. To induce hepatocarcinogenesis, diethylnitrosamine (DEN, 200 mg/kg, i.p.) was used as a tumor initiator and was given in a single dose at experimental onset. All rats were given a partial hepatectomy (PH) at 3 weeks after experimental onset. Sodium phenobarbital (PB, 0.05% in diet), GPA (0.075% in diet) and FPA (0. 075% in diet) were given from 2 to 8 weeks. Group I of the initiation control group was only given DEN. As initiation-promotion group, Group II was given DEN and then PB. Group III and IV were given DEN-PB-GPA and DEN-PB-FPA, respectively. In hematological analysis, as compared with Group I. the number of white blood cells were significantly increased in the GPA (p<0.01) and the FPA treated group (p<0.05), respectively. Natural killer (NK) cell activity by flow cytometer (FCM) analysis was higher in group of treated with the GPA (35%) than that of the FPA (27.5%), but not significant. Result of the immunohistochemical staining of the glutathione S-transferase placental form (GST-p) indicated that the number of and area of the pre-neoplastic lesions was not significantly changed in Group III and IV compared Group II, respectively. In conclusion, the GPA and the FPA treatment significantly increased the number od WBC in peripheral blood, but the enhancing NK activity and the modifying effect on the experimental hepatocarcinogenesis were not observed.

• Biomolecules & Therapeutics
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• 제3권4호
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• pp.279-287
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• 1995

This study examined the anti-cancer effects of diallyl sulfide(DAS) and/or diallyl disulfide(DDS), major components of garlic oil, with the DEN-PH model in rats, by the numbers and areas per cm$^2$ of induced glutathion S-transferase placental form(GST-P) positive foci and silver-stained nucleolar organizer regions(Ag-NORs) counts per nuclei in liver as indicator. Sprague-Dawley(SD) rats were given the diethylnitrosamine(DEN, 200 mg/kg, i.p.) as initiator and 2 weeks later, in experiment 1, rats were treated with DAS(200 mg/kg, i.g.) and/or DDS(50 mg/kg, i.g.) for 6 weeks, respectively and concomitantly and also were given the same dose of DAS and/or DDS prior to DEN treatment for 2 weeks, and in experiment II, rats were treated with potential cancer promoter, 2-acetylaminofluorene (2-AAF, 20 mg/kg, i.g.). The DAS and/or DDS were treated prior to 2-AAF for 8 weeks, respectively and concomitantly. Then the anti-promoting effects of DAS and/or DDS were assessed. All rats were subjected to the two-thirds partial hepatectomy(PH) at week 3 and sacrificed at week 8. In experiment I, DAS and/or DDS treatment only prior to DEN showed inhibition of the development of GST-P positive foci. In experiment II, DAS and/or DDS treatment prior to 2-AAF promotion showed obvious inhibition of the development of GST-P positive foci in numbers and areas and AgNORs counts. In conclusion, We found DAS and/or DDS had the preventive effects on the hepatocarcinogenesis in rats and the concomitant treatment had some additive effects compared with the each treatment and AgNORs counts correlated well with the preneoplastic hepatic lesion.

• Journal of Nutrition and Health
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• 제26권5호
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• pp.532-546
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• 1993

This study was done to investigate the effects of different dietary oils on hepatic mitochondrial lipid compositon, adenine nucleotide translocase(AdNT) and ATPase activities in carcinogen treated rats. Sixty male Sprague-Dawley rats, weighing 50∼60g, were fed three different types of dietary oil, beef tallow(BT), corn oil(CO) and sardine oil(SO) at 15% by weight for 14 weeks. Three weeks after feeding rats were intraperitoneally injected with a single dose of diethylnitrosamine(200mg/Kg BW). After five weeks rate fed 0.02% acetylaminofluorene contating diet for 6 weeks, and after seven weeks 0.05% phenobarbital containing diet for 7 weeks. At 14th week, rats were sacrificed and hepatic mitochondrial lipid composition, AdNT and ATPase activities were determined. Percent liver weight per body weight was significantly by carcinogen treatment. Analysis of mitochondrial lipid composition showed that body cholesterol and phospholipid contents were not affected by dietary oils but significantly increased by carcinogen treatment. Individual phospholipid composition as well as phosphatidyl ethanolamine/phosphatidyl choline ratio were altered by either dietary oils or carcinogen treatment. Fatty acid composition was changed by dietary oils but not much by carcinogen treatment. AdNT activity was affected by dietary oils in only carcinogen treated groups. ATPase activity was affected by dietary oils in only carcinogen nontreated groups. These data indicate that both dietary oils and caricinogen treatment can change mitochondrial lipid composition and thereby change AdNT and ATPase activities. Particularly effects of carcinogen treatment on cholesterol/phopholipid ratio, phospholipid compositon and ATPase activity were different among dietary oil groups. Therefore it is suggested that different dietary oils can somewhat modulate the changes of mitochnodrial lipid composition and membrane bound enzyme activites during hepatocarcinogenesis.

• Nutrition Research and Practice
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• 제2권4호
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• pp.234-239
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• 2008

The purpose of this study was to investigate the effects of green tea ingestion on hepatocarcinogenesis before and after its initiation. Male Sprague-Dawley rats were fed an AIN76A diet with or without green tea. Initiation was induced by a single dose (200 mg/kg) of diethylnitrosamine at week 4 and 0.02% (w/w) 2-acetylaminofluorene was supplied in the diets. The control group had free access to water for 13 weeks (CTR13). Tea infusion was provided from the beginning of the experiment for 13 weeks (PRE13) or from the post-initiation stage until week 13 (POST13). Three other groups (CTR24, PRE24 and POST24) were added to examine the longer-term effects (24 weeks) with the same experimental design. The percentage area of liver sections that were positive for hepatic placental glutathione S-transferase (GST-P), which was used as a marker of preneoplastic lesions, was smaller in PRE13 ($20.2{\pm}5.0%$, $mean{\pm}SD$) and POST13 ($26.0{\pm}4.8%$) than in CTR13 ($33.2{\pm}5.8%$, p<0.05). Over the longer period, the GST-P lesions were significantly smaller for both PRE24 and POST24 ($21.6{\pm}8.5%$ and $22.2{\pm}4.0%$, respectively) than for CTR24 ($28.6{\pm}5.1%$, p<0.05), but there was no significant difference between PRE24 and POST24. The liver content of thiobarbituric acid reactive substances was significantly lower in the tea groups than in the controls (p<0.05). However, no significant differences were observed among groups of GST activity. The results show that tea consumption exhibits a stronger short-term initiation-inhibiting ability in liver carcinogenesis, but over a longer period, the preventive effects of green tea ingestion do not differ in post- and pre-initiation.

• 한국식품위생안전성학회지
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• 제8권1호
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• pp.37-53
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• 1993

옥수수에 자연 발생하는 F. monliforme MRC 826을 옥수수에 배양하여 배양물에 존재하는 fumonisin $B_{1}$을 정성검사 한 후, 배양물질의 독성 및 발암성을 aflatoxin $B_{1}$과 비교하여 보았다. 독성 시험은 3주령의 Sprague-Dawley(SD) 암컷 랫드 10마리를 각 군당 5마리씩 2개 군으로 나누어 제1군은 시험 군으로 배양물질을 분말사료와 1 : 1로 혼합하여 1주간 급여하였고, 제 2군은 대조군으로 분말사료만을 급여하면서 실험하였다. 시험군은 급여 3~4일경부터 침울해 보였으며, 랫드 1마리당 1주간 평균 사료 섭취량은 24 g이었고, 평균 체중은 18 g 감소하였다. 부검 시 신장의 피막박리가 곤란하였고 조직 검사 결과 간장의 공포변성에 신장 세뇨관 상피세포의 괴사등의 관찰되었다. 발암성 검사 6주령의 SD 수컷 랫드 70마리를 사용하여 중기 발암성 검색법인 diethylnitrosamine-partial hepatectomy (DEN-PH) 모델로 시험하였다. 시험군은 각 군당 14마리씩 총 5개군을 두었으며 실험 0일 때 DEN을 복상내로 투여하였고, 2주후에 제 1군(양성대조군)은 aflatoxin $B_{1}$을 2ppm 농도로 첨가한 사료를, 제4군 옥수수를 5% 농도로 첨가한 사료를, 제 5군은 옥수를 2.5% 농도로 첨가한 사료를 각각 6주간 급여하였다. 실험 3주간에 간 부분 절제술을 시술하였고, 8주간 체중변화, 사료섭취량 음수량을 측정한 후 부검하여 간장은 glutathione S-transferase placental form (GST-P) 면역조직화학적 염색을 실시하였고, 뇌, 뇌하수체, 융선, 폐, 부신, 신장, 심장, 비장, 정낭선, 고환 및 간장 등은 H&E 염색을 하여 병변을 관찰하였다. GST-P 염색결과 5% 배양물질 투여군은 aflatoxin $B_{1}$투여군과 유사하게 GST-P 양성병소의 발현율이 대조군에 비하여 유의성 있는 증가를 보였다. 5% 배양물질 투여군 및 2.5% 배양물질 투여군은 옥수수 투여군에 비하여 증체율의 저하가 관찰되었고, 5% 배양물질 투여군에서 간, 신장, 고환 및 정낭선등의 체중에 대한 상대중량비, 혈액요소질소와 평균 적혈구 혈색소량 등은 옥수수 투여군에 비하여 유의성 있는 변화가 관찰되었다. 이상의 결과들을 종합해 볼 때 F. monliforme MRC 826 배양물질은 랫드의 간과 신장에 독성을 나타내었고, aflatoxin $B_{1}$과 마찬가지로 간암 촉진효과가 있는 것으로 판단되었다.

• 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

• 생명과학회지
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• 제25권3호
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• pp.307-316
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• 2015

장수풍뎅이 유충은 간질환을 치료하기 위한 민간요법으로 전통적으로 많이 사용되어 왔다. 본 연구에서는 유충 분말의 간 보호 효능과 간암억제 효능을 검증하고자 연구를 수행하였다. 먼저 장수풍뎅이 유충의 간 보호 효과를 확인하고자, 간 독성 물질인 diethylnitrosamine (DEN)을 C3H/HeN 수컷 쥐에 복강 주사하여 간 독성 실험쥐 모델을 제작하였다. DEN으로 처리된 쥐에서는 혈중 alkaline phosphatase (ALP) 농도, TUNEL positive 간세포의 숫자, 간 손상으로 인해 형성되는 duct의 개수, 간세포에서의 지방축적, Masson’s trichrome 염색에서 콜라겐 염색 정도 등, 급성 혹은 만성 간 손상과 관련된 지표들이 모두 증가되어 있는 것을 확인할 수 있었다. 하지만, 장수풍뎅이 유충 동결건조 분말을 함께 경구투여하게 되면, 이와 같은 간 손상의 지표들이 통계적으로 유의미한 수준으로 감소하게 되는 것을 확인할 수 있었다. 다음으로 항암활성 유무를 검증하기 위해, 에탄올로 유충분말 추출물을 먼저 확보한 후, solvent partition 방법을 이용하여 에탄올 추출물을 hexane, ethyl acetate, water 분획물로 분리하였다. 이들 분획물들을 여러 종류의 암세포주에 처리하였을 때, ethyl acetate 분획물이 암세포들에 대해서 아포토시스와 세포괴사와 같은 세포죽음을 유도하는 활성이 있음을 확인할 수 있었다. 더불어 ethyl acetate분획물은 암세포의 대사를 교란할 수 있었고, 오토파지를 유도할 수 있는 활성을 가지고 있었다. 결론적으로, 장수풍뎅이 유충은 독성물질로부터 간을 보호할 수 있는 성분과 암세포에 대한 세포죽음을 유도할 수 있는 활성을 가지고 있다는것을 확인하였다. 따라서, 향후 분획물들에 대한 추가적인 성분 및 활성 분석 실험으로 약리활성을 가진 물질을 분리할 수 있을 것으로 기대하고 있다.

• 한국식품과학회지
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• 제38권4호
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• pp.577-583
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• 2006

유근피 추출물을 20주간 장기 복용한 B6C3F1 마우스의 신장에서 노화 및 생체 독성의 중요한 지표로 알려진 반응성 산소종 발생 및 제거에 관여하는 효소들의 활성 현화를 관찰하였다. 실험군을 1군(대조군), 2군(암유발군-DEN을 주사하여 암유발), 3군(유근피 복용군), 4군(유근피 암치료군-DEN을 주사한 후 유근피복용), 5군(유근피 암예방군-유근피를 먹이면서 DEN 주사)등 5개군으로 나누었다. 암을 유발시킨 군에 유근피 추출물을 투여시 4군 및 5군에서 암유발군에 비해 유의적(p<0.01)으로 감소된 xanthine oxidase 효소활성을 확인하였다. Cu,Zn-SOD의 활성도는 정상군과 처리군에서 큰 차이는 없으나 Mn-SOD의 활성도는 정상군보다 암유발군에서 유의적으로 증가하는 경향을 보였다. 암유발군(2군)과 유근피 암치료군(4군)은 대조군 보다 catalase 효소이 낮았으며, 유근피 암예방군(5군)에서는 암유발군(2군)보다 catalase 활성도가 높은 것으로 나타났다. 암유발군(2군)에서는 glutathione peroxidase의 활성이 감소하는 것으로 나타났으며, 발암물질 처리와 동시에 유근피 추출물을 처리한 유근피 암예방군(5군)에서는 기타 실험군에 비해 효소활성이 매우 증가하는 것으로 (p<0.01) 나타났다. 대조군(1군)에 비해 암유발군(2군)에서 지질의 과산화도는 매우 증가하는 것으로 나타났으며, 유근피 복용군(3군)에서도 유의적으로 증가(p<0.05)하는 경향을 나타내었다. 그러나 암발생 후 유근피 추출물 식이군인 유근피 암치료군(4군)과 암발생과 동시에 유근피 추출물을 식이한 유근피 암예방군(5군)의 경우 암유발군(2군)보다 지질의 산화도가 낮은 것으로 나타났다.

• 한국수의병리학회:학술대회논문집
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• 한국수의병리학회 2002년도 추계학술대회초록집
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• pp.149-149
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• 2002

Epidemiologically the incidence of liver cancer is markedly sex-differentiated, with a much higher frequency in men than in women. In experimental animals, it is also higher in male than in female irrespective of carcinogen-induced or spontaneous tumors. Therefore, we tried to investigate the modulating effects of sex hormones in experimental hepatocarcinogenesis. For induction of liver tumors, mini-osmotic pump containing diethylnitrosamine at a dose level of 47.5mg was implanted into the peritoneal cavity of the rat at 6 weeks old. To remove the effects of male sex hormones, the animals of group 2 were castrated one week prior to DEN treatment. To see the effects of estrogen, pellet containing 1g or 10g of estradiol-3-benzoate was infused subcutaneously to the animals of group 3 and 4 one week prior to DEN treatment. The pellets were exchanged every 4 weeks until sacrifice. All animals were sacrificed at 26 weeks after DEN treatment. The tumor incidences in group 1 (DEN alone), group 2 (DEN +castration), group 3(DEN +EB 1g) and group 4 (DEN +EB 10g) were 100％ (15/15), 93.3％ (14/15), 85.7％ (12/14) and 66.7％ (10/15), respectively, showing that the value of group 4 is significantly different from that of group 1. Tumor multiplicity data of group 1, 2, 3 and 4 were 5.470.73, 2.800.51, 2.070.41 and 1.670.46, respectively, showing castration or EB treatment reduced number of liver tumors significantly (P<0.001). With immunohistochemistry and Western blotting of ER the expressions were detected in normal adjacent liver cells but decreased or lost in tumor cells. From these results we conclude that female sex hormone, especially estrogen, may act as a liver tumor suppressor, and it seemed that the down regulation of ER may be associated with liver tumor development.