• Title/Summary/Keyword: GST-p

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Hepatocarcinogenic Screening of Carbendazim Using Medium-term Carcinogenicity Bioassay (중기발암성시험기법을 이용한 Carbendazim의 간발암성 검색)

  • 성하정;이제봉;정미혜;이해근
    • Environmental Analysis Health and Toxicology
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    • v.13 no.3_4
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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.

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Effects of Pinocembrin on the Initiation and Promotion Stages of Rat Hepatocarcinogenesis

  • Punvittayagul, Charatda;Pompimon, Wilart;Wanibuchi, Hideki;Fukushima, Shoji;Wongpoomchai, Rawiwan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2257-2261
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    • 2012
  • Pinocembrin (5, 7-dihydroxyflavanone) is a flavanone extracted from the rhizome of Boesenbergia pandurata. Our previous studies demonstrated that pinocembrin had no toxicity or mutagenicity in rats. We here evaluated its effects on the initiation and promotion stages in diethylnitrosamine-induced rat hepatocarcinogenesis, using short- and medium-term carcinogenicity tests. Micronucleated hepatocytes and liver glutathione-S-transferase placental form foci were used as end point markers. Pinocembrin was neither mutagenic nor carcinogenic in rat liver, and neither inhibited nor prevented micronucleus formation as well as GST-P positive foci formation induced by diethylnitrosamine. Interestingly, pinocembrin slightly increased the number of GST-P positive foci when given prior to diethylnitrosamine injection.

Involvement of the Enhancement of Natural Killer Cell Activity on the Anti-Cancer Effect of Red Gingseng during Rat Hepatocarcinogenesis (랫드의 간압발생과정에서 홍삼의 항암효과와 자연살해세포의)

  • 강경선;이영순
    • Toxicological Research
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    • v.13 no.1_2
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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.

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The carcinogenicity study of Folpet in rats (랫드에서 Folpet의 발암성에 관한 연구)

  • Lee, Yong-soon;Cho, Jae-jin;Kang, Kyung-sun;Kim, Bae-hwan;Nam, Ki-hoan;Seo, Kwang-won;Kang, Seong-keun;Lim, Yun-kyu;Heo, Kang-jun
    • Korean Journal of Veterinary Research
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    • v.34 no.3
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    • pp.609-617
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    • 1994
  • This study was performed for assessing carcinogenicity of Folpet using medium-term carcinogenicity bioassay. Sprague-Dawley rats aged six weeks divided into four grout's and were initially given an intraperitoneal injection of diethylnirosamine at 200mg/kg body weight. Two weeks later, group 1(negative control) was treated with basal diet. A Folpet was given per oral administration to group 2(100 ppm) and goup 3(1,000 ppm). Group 4 was fed on water containing 0.05% phenobarbital sodium as a promtor for six weeks. At three weeks after beginning of the experiment, partial hepatectomy was performed in all rats. The tumor-promoting effects were examined by the numbers and areas per $cm^2$ of induced glutathion S-tranferase placetal form(GST-P) positive foci in liver, and silver stained nucleolar organizer regions(AgNORs) which have recently introduced as one of the indicators for the cell proliferative activity. As the results, Folpet didn't have tumor-promoting effects on GST-P positive foci developement and AgNORs during promoting stage after initiation, whereas phenobarbital sodium treatment group showed promoting effect. It was concluded that Folpet didn't have promoting effect at 500, 1,000 ppm using this midium-term carcinogenicity bioassay model.

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Decreased Diethylnitrosamine-induced Liver Preneoplastic Lesions by Estradiol-3-benzoate Treatment

  • Kang, Jin-Seok;Park, Ki-Dae;Ahn, Byeong-Woo;Han, Beom-Seok
    • Toxicological Research
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    • v.27 no.4
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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.

Pre- and post-initiation modulating effects of green tea ingestion on rat hepatocarcinogenesis

  • Kim, Hyung-Sook;Kim, Hee-Seon;Choi, Hay-Mie
    • Nutrition Research and Practice
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    • v.2 no.4
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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.

Cancer Chemopreventive Effect of Spirogyra Neglecta (Hassall) Kützing on Diethylnitrosamine-Induced Hepatocarcinogenesis in Rats

  • Thumvijit, Tarika;Taya, Sirinya;Punvittayagul, Charatda;Peerapornpisal, Yuwadee;Wongpoomchai, Rawiwan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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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.

Modifying Effects of Ellagic Acid in Food on Carcinogenesis (식품 중 Ellagic acid의 발암수식효과)

  • 장동덕;신동환;홍충만;조재천;한정희
    • Journal of Food Hygiene and Safety
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    • v.13 no.1
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    • pp.29-33
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    • 1998
  • The effect of ellagic acid (EA) on hepatocarcinogenesis induced by diethylnitrosamine (DEN), and promoted by phenobarbital (PB), and hepatectomized partially was investigated in male Wi star rats. All rats were injected 200 mg of DEN intraperitoneally, received 0.05 % of PB in drinking water at week 2, and hepatectomized 2/3 of liver at week 3. Rats of group 2, 3 and 4 were fed diet containing 400ppm EA for 1 week before DEN administration, for 9 weeks from beginning of experiment to sacrifice and for 6 weeks from PB treatment to sacrifice respectively. Rats of group 5, 6 and 7 were fed 800 ppm EA in the same manner as group 2, 3 and 4. Animals were killed at 8 weeks after DEN administration. The number and area of preneoplastic lesions were quantified the glutathione-S-transferase placental-form (GST-P) positive foci using immunohistochemical method. Decrease of number and area of the positive foci was observed in the rats fed 400 ppm EA for 9 weeks. In addition, the reduction of the foci can examine in all group fed 800 ppm EA. In conclusion, EA inhibited the hepatocarcinogenesis induced by DEN when it was administrated 800 ppm.

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Different Sources of $\omega3$ Fatty Acids at the Fixed Ratio of p/s Affect Glutathione Dependent Enzymes in Rat Hepatocarcinogenesis (간세포 암화과정에서 p/s 고정비율과 $\omega3$ 지방산 급원에 따른 전암성 병변과 Glutathione 의존 해독화 효소계에 미치는 영향)

  • 이해정;김혜경;최혜미
    • Journal of Nutrition and Health
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    • v.36 no.8
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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)