• 한국식품위생안전성학회지
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• 제5권4호
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• pp.179-186
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• 1990

이 연구는 수입 축산식품중에 잔류해서 사람에게 해를 줄 수 있는 여러 합성 홀몬의 발암성을 알아보기 위하여 수행한 연구이다. 6주령의 F344 랫드를 5군으로 나누어 발암유발물질인 diethylstilbesterol(DENA)를 체중 kg당 200 mg을 복강 내 투여하고, 시험게시 제2주에서 시험종료시까지 제 1, 2, 3,군에 각각 diethylstilbesterol(DES), ethynylestradio($EE_2$), bovine somatotrophin(BST)을 투여하고, 제 4군에는 발암촉진이 잘 알려진 phenobabital을 투여하였으며, 제 5군은 대조군으로 기초사료만을 급여하였다. 동시에 모든군의 랫드는 D-galactosamine을 체중 kg 당 300 mg을 복강내로 1회 투여하였으며, 간변화의 증폭을 위하여 2/3 간부분 절제를 시험개시 제 5주에 실시하였다. 시험종료시 부검후 랫드의 간장은 GST-P에 대한 면역조직화학적 염색을 실시하여 발암성을 검색하였다. 두개의 합성 에스트로젠 홀몬($EE_2$, DES)은 대조군과 비교하였을 때 발암성이 있는 것으로 생각되어지고, BST는 발암성이 없는 것으로 생각된다.

• 대한지역사회영양학회지
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• 제4권2호
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• pp.239-247
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• 1999

Six-week-old Sprague Dawley rats were fed the diets of 20% casein or soy protein. Two weeks after the feeding, hepatocellular chemical carcinogenesis was initiated by diethylnitrosamine(DEN), and promoted by the diet containing 0.01% 2-acetylamino-fluorene(AAF) and two-thirds partial hepatectomy(PH). The animals were sacrificed at 8 weeks after the DEN injection. The area of placetal glutathione S-trnasferase(GST-P) positive foci, the activities of several enzymes in cellualr antioxidant enzyme systems and glucose 6-phosphatase were determined to investigate the mechanism of the anticarcinogenic effect by the dietary proteins. In another set of experiments, the drinking water of rats fed casein was supplemented with 1.5% inositol hexaphosphate(InsP6) to elucidate whether it has the comparable anticancer action of soy protein. The area and number of GST-P positive foci in the soy protein group were significantly(p<0.05) lower than those inthe casein group. The livers of rats fed casein showed moderate fattydegeneration and larger hyperplastic nodules than those of rats fed soy protein. In another set of experiments, the area and number of GST-P positive foci in the rats fed casein supplemented with InsP6 were not significantly different from those in the rats fed casein or soy protein. The lipid peroxidation of rats fed different protein sources showed no significant difference. Glutathione S-transferase(GST) activities were increased significantly(p<0.05) by carcinogen treatment in all dietary groups. Glucose 6-phosphatase(G6Pase) activities were decreased by carcinogen treatment, and hence showed a reverse relationship(r=-0.695, p<0.01) to the GST-P positive foci. Therefore, the activities in the rats fed casein were lower than those in the rats fed soy protein. These results suggest that the soy protein seems to be more anti-carcinogenic than casein by decreasing the preneoplastic lesion and by increasing the membrane stability but inositol hexaphosphate, a component of soy protein, may not be protective against hepatocarcinogenesis.

• 한국환경성돌연변이발암원학회지
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• 제16권2호
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• pp.109-116
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• 1996

To study the effect of dietary $\omega 6/\omega 3$ fatty acid ratios on the preneoplastic lesions and lipid peroxidation in rat hepatocellular chemical carcinogenesis, placental glutathione S-transferase(GST-P) positive foci area and numbers, glucose 6-phosphatase(G6Pase) activity, thiobarbituric acid reactive substances (TBARS) were measured. Male Sprague-Dawley rats were fed 5 different diets-low $\omega 6/\omega 3$ ratio with fish oil (Low-F), low $\omega 6/\omega 3$ ratio with perilia oil(Low-P), moderate ratio with perilia oil(Moderate), blend of 10 different commercial fats and oils(High-BL) and high $\omega 6/\omega 3$ ratio(High)-for 8 weeks. Hepatocarcinogenesis was induced by modified Ito model. The area of GST-P positive loci was the lowest in Moderate group and in ascending order of Low-F < Low-P < High-BL < High. But statistically, only Moderate and High groups were significantly different. The number of GST-P positive foci showed the same trend as foci area. The activities of G6Pase, membrane stability marker, were increased as $\omega 6/\omega 3$ ratio decreased. Lipid peroxidation values (TBARS) were the lowest in Low-F group and it is significantly different from Moderate, High-BL and High groups. When dietary $\omega 6/\omega 3$ ratio was moderate(4.06), hepatocarcinogenesis was suppressed compared with high or low $\omega 6/\omega 3$ ratios. Blend fat, commonly consumed among Koreans, did not show any suppressive effect on carcinogenesis because of high ratio(6.7). These results suggest that dietary $\omega 6/\omega 3$ ratio influences hepatocellular chemical carcinogenesis. It is recommended that appropriate $\omega 6/\omega 3$ ratio should be around 4.0. and we recommend to use more $\omega 3$ fatty acid in food preparation to reduce the risk of hepatocarcinogenesis.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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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.

• BMB Reports
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• 제30권1호
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• pp.73-79
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• 1997

This study was designed to investigate the effects of dietary garlic powder on cytochrome P450 enzymes and membrane stability in murine hepatocarcinogenesis initiated by diethylnitrosamine (DEN). Male Sprague-Dawley rats received a single intraperitoneal injection of DEN (200 mg/kg body wt) dissolved in saline. After 2 weeks on a basal diet, animals were fed diets containing 0. 0.5. 2.0. or 5.0% garlic powder for 6 weeks, and were subjected to two-thirds partial hepatectomy. The areas of placental glutathione S-transferase (GST-P) positive foci were inhibited in rats fed with garlic diets. GST-P is the most effective marker for DEN-initiated lesions. Hepatic microsomal lipid peroxidation was significantly decreased in rats fed with 2.0 and 5.0% garlic powder diets compared with that observed in the control animals and hepatic microsomal glucose 6-phosphatase (G6Pase) activity was found to increase significantly in rats fed 0.5 and 2.0% garlic powder diets. Thus as little as 0.5% garlic powder has a positive effect on the stability of hepatic microsomal membranes. p-Nitrophenol hydroxylase (PNPH) activity and the level of cytochrome P450 2E1 protein in the hepatic microsomes from rats fed diets containing 2.0 and 5.0% garlic powder were much lower than those of control microsomes. Rats fed 5.0% garlic powder diets exhibited the lowest P450 2E1 activity and protein levels among groups. Pentoxyresorufin O-dealkylase activity and immunoblot (cytochrome P450 2B1) analyses were not different between groups. However, the levels of cytochrome P450 1A1/2 protein in rats fed 0.5 and 2.0% garlic powder were significantly induced compared to controls. These results suggest that 2.0% garlic powder is effective in inhibiting the areas of GST-P positive foci, modulating certain isoforms of cytochrome P450 enzymes and stabilizing the hepatic microsomal membrane. Thus, the selective modification of cytochrome P450 enzymes and membrane stability by dietary garlic powder may influence areas of GST-P positive foci and chemoprevention of post-initiation of rat hepatocarcinogenesis.

• Journal of Nutrition and Health
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• 제38권5호
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• pp.364-372
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• 2005

This study is designed to examine the effects of dietary supplementation with vitamin E and dehydroepiandrosterone (DHEA) on the formation of preneoplastic lesions in diethylnitrosamine (DEN) induced rat hepatocarcinogenesis. All Weaning male Sprague-Dawley rats were initiated by a single dose of DEN (200mg/kg body weight), subjected to two­thirds partial hepatectomy 3 weeks later and were sacrificed 8 weeks after DEN initiation. Two weeks after initiation, rats were fed Purina purified rodent diet 5053 (Ralston Purina Rat chow, USA) with $1.5\%$ (15,000 IU/kg diet) vitamin E, $0.5\%$ DHEA and both of those supplemented diet for 6 weeks. Placental glutathione S-transferase (GST-P) positive foci, the activities of catalase, total-glutathione peroxidase (GPx) , glutathione reductase (GR), glutathione S-transferase (GST) and thiobarbituric acid reactive substances (TBARS) contents were decreased significantly by vitaimin E supplement. On the other hand GST-P positive foci number, Cu/Zn-superoxide dismutase (SOD) and glucose 6-phosphatase (G6Pase) activities weren't changed by vitamin E supplement. It might suggest that protective effect of vitamin E against hepatocarcinogens is not involved in the formation of the GST-P positive foci but related to the expansion of that. It seemed that vitamin E supplement helped endogenous defense system in carcinogenesis by decreasing TBARS contents, $H_2O_2$, organic peroxides. Therefore, vitamin E seemed to protect cell from free radical damage in carcinogenesis. By DHEA supplement liver weight and liver/body ratio were increased, the area and number of GST-P positive foci, the activities of catalase, GR, total GPx, GST and the TBARS contents were decreased significantly. On the other hand Cu/Zn-SOD and G6Pase activities weren't changed by DHEA supplement. In hepatocarcinogenesis the activities of antioxidant enzymes weren't increased by DHEA supplement. DHEA did not increase the oxidative stress, while DHEA seems to have anticarcinogenic effect in rats hepatocarcinogenesis.

• Journal of Nutrition and Health
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• 제34권8호
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• pp.833-842
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• 2001

The purpose of this study is to determine the effect of dietary proteins and fats on the hepatic histological changes, membrane stability, and drug-metabolizing enzyme activities during chemically induced rat hepatocarcinogenesis. Weanling Sprague-Dawley rats were fed the diet containing 20% casein or soy protein isolate and 15% perilla or corn oil for 10 weeks. Hepatocarcinogensis was initiated with diethylnitrosamine(DEN), and the rats were fed diets containing 0.02% 2-acetylaminofluorene(AAF) followed by 0.05% phenobarbital (PB). The scores of histological changes were decreased in treated rats fed soy protein diet compared to those find casein diet. Liver weights were significantly increased by AAF and PB treatment in rats fed casein diets in both oil groups. Glucose 6-phosphatase(G6Pase) activities, an index of membrane stability, were significantly reduced by AAF and PB treatment in rats find casein diets, and were lower in casein diet compared to soy protein diet groups. Especially, the activities were the highest in the rats fed soy protein-perilla oil diet. Lipid peroxide values also were increased by AAF and PB treatment in rats fed casein diet. Aniline hydroxylase activities were not influenced by protein and fat sources. Glutathione-dependent enzyme activities were increased by AAF and PB treatment. Linoleic and arachidonic acid content were increased in rats fed corn oil diet, and linolenic and eicosapentaenoic acid contents were increased in rats fed perilla oil diet. Our results suggest that soy protein isolate inhibit the abnormal histological changes in liver, possibly by maintaining the membrane stability during chemically induced rat hepatocarcinogenesis. Soy protein may be protective against the hepatocarcinogenesis induced by chemical carcinogen.

• Journal of Nutrition and Health
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• 제36권8호
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• pp.785-792
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• 2003

This study is conducted to determine the effects of dietary source of $\omega$3 fatty acids on preneoplastic foci and the glutathione dependent enzymes in rat hepatocarcinogenesis initiated by diethylnitrosamine (DEN). Male Sprague-Dawley rats were fed one of three diets containing 10% (w/w) fats fixed p/s = -1.0 and $\omega$6/$\omega$3 ratio = -0.4 or 4.0 ; fish oil-com oil blended (FC), com oil-beef tallow-fish oil blended (CF), com oil-beef tallow-perilla oil blended (CP), from gestation period. At 10 weeks, animals of experimental groups were injected intraperitoneally with DEN (200 mg/kg body weight) and two-thirds partial hepatectomy was carried out 3 weeks later and were sacrificed 8 weeks after DEN initiation. The area and number of glutathione S-transferase placenta (GST-P) positive foci were significantly decreased in rats fed diets containing fish oil (FC and CF) than those fed perilla oil diet (CP). Fish oil feeding significantly increased the activities of glutathione dependent enzymes. Rats fed diets containing fish oil (FC and CF) significantly increased the glutathione (GSH) content and the activities of glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST). Glutathione dependent enzymes had significantly negative correlation with GST-P positive foci. Glucose 6-phosphatase (G6Pase) was increased in rats feeding fish oil. Thiobarbituric acid reactive substances were not different among groups. Therefore, the preventive effect against hepatocarcinogenesis might be explained by induction of the glutathione dependent enzymes and G6Pase. (Korean J Nutrition 36(8): 785∼792, 2003)

• 한국식품영양과학회지
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• 제30권1호
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• pp.119-126
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• 2001

Effects of Sardine Oil Feeding and Vitamin E Supplementation on Histopathological Changes and $\alpha$-L-fucosidase activity in experimental hepatocarcinogenesis. Sprague-Dawley rats weighing 80~90 g were fed the diet containing either 15% corn oil (CO) or sardine oil (SO) with or without vitamin E supplements (dl-$\alpha$-tocopherol acetate 800 IU/kg diet) for 8 weeks. After 2 weeks of feeding, the rats were given a single intraperitoneal injectin of diethylnitrosamine (DEN, 200 mg/kg BW). From the fifth week, rats were given 0.02% acetylaminofluorene (AAF) in diet for 4 weeks. At the seventh week, 0.05% phenobarbital in liver and hepatic glutathione S-transferase palcental form positive (GST-P+) foci were examined by Hematoxylin& Eosin (H&E) staining and immunohistochemical method, respectively. Serum $\alpha$-L-fucosidase activity was determined. The livers fromt he carcinogen treated rats showed significantly increased formation of GST-P+ foci at sacrifice points while the livers fromthe non-carcinogen treated groups showed almost no foci. Although GST-P+ foci formation was not affected by dietary oil, it was increased unexpectedly by vitamin E supplementation. Histopathological changes were similar to patterns of GST-P+ foci formation in almost all groups. Serum $\alpha$-L-fucosidase activities were increased by carcinogen treatment in all dietary groups. $\alpha$-L-fucosidase activities were positively correlated with GST-P+ foci formation. There results suggest that excessive vitamin E supplementation can enhance hepatocarcinogenesis although the mechanisms involved are not clearly understood.

• Journal of Nutrition and Health
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• 제31권6호
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• pp.1014-1023
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• 1998

The influences of fish oil and different levels of vitamin I supplement on hepatocellular chemical carcinogenesis have been studied. Male Sprague-Dawley rats received diethylnitrosamine (DEN)(200mg/kg body weight) and were subjected to two-thirds partial hepatectomy to induce murine chemical hepatocarcinogenic procedure. Placental glutathione S-transferase(GST-P) positive foci area, antioxidant enzymes(Cu/Zn-superoxide dismutase(SOD), catalase, glutathione reductase (GR), total- glutathione peroxidase (TGPx), glutathione S -transferase (GST)), glucose 6-phosphatase (G6Pase) activities, and lipid peroxidation of microsomes(thiobarbituric acid reactive substances (TBARS)) were measured. Experimental animals were fed 15% corn or fish oil with 0, 40, 1,000, 10,000IU vitamin E /kg diet for 8 weeks. Vitamin E supplements decreased the area of GST-P positive foci in both groups. The higher the vitamin E levels, the smaller the area of GST-P positive foci were noticed. Compared to 0 IU vitamin E, 40 IU in corn oil and 1,000 IU in fish oil groups were effective in decreasing G57-P positive foci area. Fish oil groups tended to have smaller area of GST-P positive foci. fish oil groups showed lower body weight, lower activities of Cu/Zn-SOD and TGPx, higher TBARS contents, higher activities of GST, catalase, G6Pase, GR and higher liver/body ratio than corn oil groups. As the level of vitamin I increased, GST-P positive foci count, catalase activities, and TBARS tended to decrease. G6Pase activities tended to increase in both groups. At higher vitamin E levels, GST activities tended to decrease in fish oil groups. These results suggest that vitamin I has suppressive offects on hepatocellular chemical carcinogenesis probably through antioxidant eH:cts decreasing TBARS contents, $H_2O$$_2$, and organic peroxides. fish oil tended to have greated suppressive offects than corn oil on hepatocellular carcinogenesis. (Korean J Nutrition 31(6) : 1014-1023, 1998)