• 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.

• 한국환경성돌연변이발암원학회지
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• 제11권2호
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• pp.118-133
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• 1991

신생랫드를 이용한 다장기 발암모델의 전암단계 병변에서 간장의 GST-P 활성도와 발암 과정에 영향을 미치는 phenobarbital (PB)의 발암촉진효과 및 병리조직학적 소견을 관찰하였다. 신생랫드를 150마리 3군으로 나누어 diethylnitrosamine (DEN : 100mg/kg,i,p.), N-me-thyl-N-nitrosourea (MNU : 20mg/kg,i,p.), N-bis(2-hydroxypropyl)nirtosamine(DHPN : 0.1% D. W)을 각각 0, 3, 6 주에 투여하였다. 또한 PB (0.5% in basal diet)를 7주부터 계속 투여하여 8, 12, 20주에 경시적인 부검을 실시하였다.

• Journal of Nutrition and Health
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• 제35권6호
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• pp.643-649
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• 2002

This study was done to investigate effects of ${\gamma}$-irradiated pork feeding on the formation of glutathione S-transferase placental form positive (GST-P$^{+}$) foci, lipid peroxidation, cytochrome P450 system and microsomal glucose 6-phosphatase activity in diethylnitrosamine (DEN)-initiated rat hepatocarcinogenesis. Weaning Sprague-Dawley male rats were fed the diet containing ${\gamma}$-irradiated ground pork at the dose of 0, 3, 10, 30 kGy as a 20％ of protein source for 8 weeks. One week after feeding, rats were intraperitoneally injected twice with a dose of DEN (50 mg/kg BW). As a promote.,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 showed a increasing tendency. Cytochrome P450 content was also significantly increased while microsomal glucose 6-phophatase activity was significantly decreased with DEN treatment. However the 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 rats fed gamma irradiated pork were tended to be decreased by high dose of irradiation, but were not significantly different. These results might imply that the consumption of low dose of gamma irradiated pork does not affect the formation of hepatic GST-P$^{+}$ foci and lipid peroxide and membrane stability.ability.

• 한국식품영양과학회지
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• 제28권3호
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• pp.646-653
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• 1999

This study was done to investigate the effect of ${\gamma}$ irradiated beef feeding on antioxidant vitamin levels and defense enzyme activities in diethylnitrosamine(DEN) initiated rats. Weaning Sprague Dawley male rats were fed the diet containing ${\gamma}$ irradiated ground beef at the dose 0, 3, 5 kGy 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, serum level of vitamin C, serum and hepatic levels of retinol and tocopherol were determined. In addition, activities of cytosolic glutathione peroxidase, glutathione reductase, glutathione S transferase, catalase and hepatic superoxide dismutase(SOD) were measured. By ${\gamma}$ irradiation, there was no significant effect on serum and hepatic levels of vitamin C and tocopherol except a significant decreasing effect on hepatic retinol level. There was also no significant effect on the activities of enzymes involved in antioxidative defense system, However, DEN treatment led to a significant increase in activities of glutathione reductase and glutathione S transferase while the activity of glutathione peroxidase was decreased. The activities of hepatic SOD and catalase were not changed by DEN treatment. Overall results indicate that the consumption of low dose of ${\gamma}$ irradiated beef does not affect antioxidative defense system.

• 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.

• BMB Reports
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• 제57권2호
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• pp.98-103
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• 2024

The mammalian sirtuin family (SIRT1-SIRT7) has shown diverse biological roles in the regulation and maintenance of genome stability under genotoxic stress. SIRT7, one of the least studied sirtuin, has been demonstrated to be a key factor for DNA damage response (DDR). However, conflicting results have proposed that Sirt7 is an oncogenic factor to promote transformation in cancer cells. To address this inconsistency, we investigated properties of SIRT7 in hepatocellular carcinoma (HCC) regulation under DNA damage and found that loss of hepatic Sirt7 accelerated HCC progression. Specifically, the number, size, and volume of hepatic tumor colonies in diethylnitrosamine (DEN) injected Sirt7-deficient liver were markedly enhanced. Further, levels of HCC progression markers and pro-inflammatory cytokines were significantly elevated in the absence of hepatic Sirt7, unlike those in the control. In chromatin, SIRT7 was stabilized and colocalized to damage site by inhibiting the induction of γH2AX under DNA damage. Together, our findings suggest that SIRT7 is a crucial factor for DNA damage repair and that hepatic loss-of-Sirt7 can promote genomic instability and accelerate HCC development, unlike early studies describing that Sirt7 is an oncogenic factor.

• 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.

• 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.

• Journal of Nutrition and Health
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• 제33권1호
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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)