• BMB Reports
• /
• v.28 no.5
• /
• pp.420-426
• /
• 1995

This study was conducted to compare the effects of n-6 linoleic acid and n-3 linolenic acid on lipid peroxidation and the activities of enzymes defending against oxidation, which are involved in the tumor promotion, and histolOgical changes of hepatocarcinogen treated rat liver. In this study, weanling male Sprague-Dawley rats were fed one of three diets, containing 15% (w/w) of beef fat (BF), com oil (CO) or perilla oil (PO), for 11 weeks. During the 3rd week, experimental groups were injected with 2-AAF (50 mg/kg of BW) intraperitoneally 3 times. Findings show that the com oil diet group has greater liver MDA content than the beef fat and perilla oil diet groups. Also, it is observed that the perilla oil diet group has lower MDA content than beef fat and com oil diet groups, even though perilla oil is more desaturated than beef fat and com oil. In terms of activity, mixed-function oxidase activity is not Significantly affected by the different dietary fats and 2-AAF treatment. GSH-peroxidase, GSH-reductase and GSH-Stransferase activities are significantly higher in the CO+AAF group than those of the other groups. GST and GSH-Px are activated by 2-AAF treatment in the com oil diet group only. The hepatocytes of the BF+AAF group were the most severely degenerated, the second was the CO+AAF group and the least was the PO+AAF group. It was also found that dietary com oil increased lipid peroxidation and activated defense enzymes against oxidation in liver, but dietary perilla oil did not, or supressed defense enzymes. Therefore it is concluded that dietary n-3 linolenic acid in perilla oil inhibits lipid peroxidation and carcinoenesis in rat liver following 2-AAF treatment.

• Environmental Analysis Health and Toxicology
• /
• v.13 no.3_4
• /
• pp.71-75
• /
• 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.

• Toxicological Research
• /
• v.7 no.1
• /
• pp.93-112
• /
• 1991

This study was carried out to investigate the various factors on induction of experimental hepatocarcinogenesis in Sprauge-Dawley rats. The experimental animals were divided into three Experiment. Experiment I, II and III were began rats with initial age of 6, 16 and 55 weeks, respectively. All Experiment were injected intrapertioneal with diethylnitrosamine (DENA` 200 mg/kg) as an intiator and group 3, 4 of Experiment I, II and III were fed on diet containing 0.02% 2-acetylaminofluorene (2-AFF) as a promoter for 6 weeks. Three weeks after two-thirds partial hepatectomy was performed in group 2, 4 of Experiment I & II and group 3 of Experiment III.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.24 no.6
• /
• pp.867-873
• /
• 1995

This study was done ot investigate the effect of chronic alcohol feeding and acetylaminofluorene(2-AAF) treatment on hepatic mitochondrial ATPase activity andmembrane lipid composition. Male Sprague-Dawley rats, weighing 120~125g, were fed for 6 weeks on a liquid diet containing 35% of calories as ethanol. After 4 weeks of experiment diet feeding, 2-AAF(100mg/kg body weight) was injected twice a week intraperitoneally. Body weight and percent liver weight per body weight were significantly changed by ethanol feeding. Hepatic mitochondrial ATPase activity significantly decreased by ethanol feedings but not by 2-AAF treatment. In comparison to control, the ATPase activity of ethanol-AAF group decreased 29.3%. Since phospholipid(PL) content of mitochondria has an interaction effect between ethanol and 2-AAF treatment, 2-AAF treatment significantly increased phospholipid content in only ethanol fed group. Total cholesterol(C) level of mitochondria significantly increased by ethanol feeding. Consequently C/PL ratio of ethanol group was significantly higher than that of control group. The analysis of mitochondrial PL composition showed that cardiolipin(CL) significantly increased by 2-AFF treatment in control group. Phosphatidyl choline(PC) significantly increased by ethanol feeding, whereas PC significanlty decreased and phosphatidyl ethanolamine(PE) significantly increased by 2-AAF treatment. 2-AAF treatment also showed a significant increase in PE/PC ratio. Fatty acid patterns of mitochondria were also changed by either ethanol or 2-AAF although the severity of the changes was not great. These data suggest that the reduced mitochondrial ATPase activity in ethanol-AAF group may be a consequence of a changes in mitochondrial membrane lipid composition such as PE/PC ratio, C/PL ration and fatty acid patterns.

• Journal of Food Hygiene and Safety
• /
• v.6 no.1
• /
• pp.13-26
• /
• 1991

This study was performed for searching for non-hepatectomy medium-term bioassay model by using newborn female rats. Newborn female Sprague-Dawley rats (1 day old) were given an intraperitoneal injection of 150 mg/kg of diethylnitrosamine (DENA). After three weeks, all rats were weaned and divided into three groups. Group 1 were fed on diets containing 0.01% 2-acetylaminofluorene (2-AAF) as a promoter for three weeks. Group 2 were given 0.05% phenobarbital (PB) in drinking water as a promoter for 8 weeks. Group 3 was control group. The autopsy was carried out at 4 weeks and 8 weeks after weaning. Preneoplastic lesions were indentified with immunohistochemical staining for glutathione S-transferase placental form (GST-P). In liver weight to body weight ratios, group 2 showed significant difference from group 1 (p<0.001) at 4 weeks after weaning. Group 1 and group 2 showed significant difference from group 3 at 8 weeks after weaning (p<0.0I, p<0.001), respectively. In quantitative analysis for GST-P positive lesion area by using Image Analyzer, group 1 and group 2 represented significant difference in comparison with group 3 at early 4 weeks after weaning (p

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1994.04a
• /
• pp.318-318
• /
• 1994

Addition of AAF to murine splenocytes culture produced a dose-related suppression of lymphoproliferative response to lipopolysaccharide (LPS). The time course of the suppression showed that a significant inhibition was occured after a 18 hr AAF treatment. Total protein kinase C activity in splenocytes was decreased to 72% of control level after a 18 hr AAF treatment. Phosphorylation of a PKC specific 80 kDa protein was increased by LPS and AAF down-regulated LPS-induced PKC activity. LPS-induced phosphorylation of overall proteins in membrane and cytosolic fraction were also decreased by the treatment of AAF. A significant increase of PKC activity in membrane fraction was noticed within 10 min of AAF treatment compared to LPS alone and then gradually decreased to LPS level in 60 min. Meanwhile, PKC activity in cytosolic fraction was increased slightly in 10 min by the treatment of AAF and then decrease to 80% LPS level in 30 min. These results suggested that suppressive effect of AAF on LPS-induced lymphoproliferative response may be associated with the down-regulation of PKC and other susceptible kinases in spleen cells.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1993.04a
• /
• pp.167-167
• /
• 1993

신물질의 면역독성 평가방법을 체계화하고 독성기작을 규명하고저 기존 면역독성 유발물질을 대상으로 in vivo 및 in vitro 실험을 수행하였다. 먼저 비장세포-간세포 공동배양 시스템을 대사를 요구하는 물질의 면역독성 평가에 in vitro system으로 사용하고저 DMN을 대상으로 공동배양 조건 및 배지에 대한 연구를 수행하였다. 비장세포원으로 BALB/c 마우스를 사용하였고, 간세포원으로 Spraque-Dawley 랫드를 사용하였다. DMN은 홀몬이 첨가된 배지에서 항체 형성반응을 크게 저하시켰으나 배지의 종류에 따른 DMW의 대사에는 큰 영향이 없었다. 또한 procarcinogen인 DMBA에 의한 면역독성은 DMBA의 대사물에 의해 유도되며 DNA가 primary target 임을 규명하였으며, 2-acetylaminofluorene (AAE)에 의한 면역 억제작용의 기작에서 인터루킨의 영향에 대해 연구하였다. Protein methylase inhibitor인 SF와 SIBA웨 면역억제 작용을 연구한 결과 lymphoproliferative response에서 protein methylase 가 직접 또는 간접적으로 관여함이 입증되었다.

• The Korean Journal of Food And Nutrition
• /
• v.23 no.2
• /
• pp.276-284
• /
• 2010

The effects of different dietary fatty acids on the hepatic glutathione S-transferase(GST-P) positive foci and glutathione related enzyme system were investigated in carcinogen treated rats. Weaning male Sprague Dawley rats were divided into three groups and fed the diets of 15% corn(CO), perilla(PO), and sardine oil(SO), respectively. Hepatocellular carcinogenesis was initiated with diethylnitrosamine(DEN) and then fed the diet containing 0.02% 2-acetylaminofluorene(2-AAF) followed by 0.05% phenobarbital for 10 weeks. The hepatic tissues were homogenized and centrifugated to prepare microsomal and cytosolic fractions. The enzyme activities of hepatic glutathione S-transferase(GST), glutathione reductase(GR), and glutathione peroxidase(GPx) were determined from cytosolic fractions. The number of GST-P hyperplastic nodules was the highest in corn oil group at 6th week, the early stage of hyperplastic nodule formation. GST activities were increased significantly by carcinogens in all dietary groups after 6th wk. GR activities followed the same trend as GST activities. GPx activities were decreased by carcinogens in all dietary groups at 10th week. In this experiment, corn oil diet may have promotive effect on hyperplastic nodule formation during the early promotional stages of chemical carcinogenesis.

• Culinary science and hospitality research
• /
• v.4
• /
• pp.129-146
• /
• 1998

The effects of vitamin E supplement on 15%(w/w diet) perilla or corn oils were studied in rat hepatocellular chemical carcinogenesis induced by modified Solt & Farber model, which consists of 20mg/kg body weight diethylintrosamine(DEN) injection, 3 weeks feeding of 0.02%2-acetylaminofluorene(2-AAF) and partial hepatectomy. The area of placental glutathione S-transferase(GST-P) positive foci tended to be smaller in perilla oil group had lower thiobarbituric acid reactive substances(TBARS) CONTENT. Fatty acid compositions in microsomal membrane were reflected by dietary fatty acid compositions, and not affected by carcinogen treatment or vitamin E supplement. By vitamin E supplement, linolenic acid contents of perilla oil group were much increased. By carcinogen treatment, membrane stability decreased significantly in corn oil, but maintained in perilla oil groups Vitamin E supplemental effect was noticed only in the corn-carcinogen group. Perilla oil may prevent hepatocarcinogenesis by maintaining membrane stability and by reducing cytochrome P-450 content. Vitamin E supplement did not seem to have the effect on hepatocarcinogenesis, but prevented lipid peroxidation, reduced cytochrome P-450 content and maintained membrane stability.

• Biomolecules & Therapeutics
• /
• v.3 no.4
• /
• pp.279-287
• /
• 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.