• BMB Reports
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• v.30 no.1
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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.

• BMB Reports
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• v.35 no.6
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• pp.615-622
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• 2002

The purpose of this study was to determine the effects of dietary garlic powder on diethylnitrosamine (DEN)-induced hepatocarcinogenesis and cytochrome P450 (CYP) enzymes in weaning male Sprague-Dawley rats by using the medium-term bioassay system of Ito et al. The rats were fed diets that contained 0, 0.5, 2.0 or 5.0% garlic powder for 8 weeks, beginning the diets with the intraperitoneal (i.p.) injection of DEN. The areas of placental glutathione S-transferase (GST-P) positive foci, an effective marker for DEN-initiated lesions, were significantly decreased in the rats that were fed garlic-powder diets; the numbers were significantly decreased only in the 2.0 and 5.0% garlic-powder diets. The p-nitrophenol hydroxylase (PNPH) activities and protein levels of CYP 2E1 in the hepatic microsomes of the rats that were fed the 2.0 and 5.0% garlic powder diet were much lower than those of the basal-diet groups. Pentoxyresorufin O-dealkylase (PROD) activity and CYP 2B1 protein level were not influenced by the garlic-powder diets and carcinogen treatment. Therefore, the suppression of CYP 2E1 by garlic in the diet might influence the formation of preneoplastic foci during hepatocarcinogenesis in rats that are initiated with DEN.

• Korean Journal of Veterinary Research
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• v.32 no.4
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• pp.629-633
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• 1992

Caffeine이 랫드의 간조직에서 diethylnitrosamine(200mg/kg B.W., DEN)에 의해 유도되는 preneoplastic altered foci형성의 promotion단계에 미치는 효과를 관찰한 바 다음과 같은 결과를 얻었다. Altered foci의 지표로 사용되는 glutathione S-transferase(GST-P)-positive foci의 수는 caffeine 음수 $m{\ell}$당 2mg 병행투여군($3.10{\pm}2.74$) 및 1mg병행 투여군($5.86{\pm}2.83$) 모두에서 DEN 단독투여 대조군($11.55{\pm}5.82$)에 비하여 현저히 낮게 나타났으며 면적 또한 caffeine 2mg 병행투여군($0.13{\pm}0.11$), 1mg 병행투여군($0.21{\pm}0.12$)에서 DEN 단독투여 대조군($0.76{\pm}0.33$)에 비하여 유의성있는 낮은 수치가 관찰되었다. 간 세포배양에서 unscheduled DNA synthesis(UDS)는 DEN($250{\mu}g/m{\ell}$ of medium)단독처리군에 비하여 caffeine($200{\mu}g/m{\ell}$ of medium) 처리시 약 70% 감소하였다. 이러한 결과는 caffeine이 간암발생의 promotion단계에 작용하여 억제효과를 나타냄을 암시하며 이는 DNA회복의 억제와 관계됨을 알 수 있었다.

• Korean Journal of Veterinary Research
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• v.31 no.3
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• pp.337-342
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• 1991

Caffeine이 랫트의 간조직에서 diethylnitrosamine(200mg/kg B.W., DEN)에 의해 유도되는 preneoplastic altered foci형성의 initiation단계에 미치는 효과를 관찰한 바 다음과 같은 결과를 얻었다. Altered foci의 지표로 사용되는 glutathione S-transferase(GST-P)-positive foci의 수는 caffeine 음수수 ml 당 2mg병행투여군 $(7.48{\pm}3.33)$ 및 1mg 병행 투여군 $(7.50{\pm}3.32)$ 모두에서 DEN 단독투여대조군$(14.08{\pm}5.16)$에 비하여 현저히 낮게 나타났으며, 면적 또한 caffeine 2mg병행투여군 $(0.29{\pm}0.17)$, 1mg병행투여군 $(0.30{\pm}0.13)$에서 DEN단독투여대조군 $(0.46{\pm}0.21)$에 비하여 유의성 있는 낮은 수치가 관찰되었다. 이러한 결과는 caffeine이 간암발생의 initiation 단계에 작용하여 억제효과를 나타냄을 암시하였다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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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.

• Journal of Food Hygiene and Safety
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• v.8 no.1
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• pp.37-53
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• 1993

F. moniliforme MRC 826, a common fungal contaminant of com, has been known to produce a group of mycotoxins, the fumonisins. By thin layer chromatography, fumonisin $B_{1}$ was detected in the F. moniliforme MRC 826 com culture material(CM) extracts. This study was performed to compare the toxicity and carcinogenicity of F. moniliforme MRC 826 CM with those of aflatoxin $B_1(AFB_1)$ in rats. The toxicity was tested over a period of 7 days in ten female Sprague-Dawley (SD) rats. Treatment group were fed a 1 : 1 mixture(wt/wt) of ground CM and basal diet in powder form, while other negative control group were given basal diet alone. The principal pathological changes in rats treated with 50% CM were hepatocellular hydropic degeneration and renal tubular necrosis. The cancer-promoting activity of CM was evaluated in the rat liver diethylnitrosamine-two thirds partial hepatectomy(DEN-PH) model for carcinogenesis. 70 male SO rats(ca. 170 g) were randomized into 5 groups. Group I served as the positive controls and received the basal diet containing 2 ppm $AFB_{1}$ group 2 received 5% CM, group 3 received 2.5% CM, group 4 received 5% normal com and group 5 received 2.5% normal com. 5% treated group showed cancer promoting activity in rat liver using DEN as initiator and the induction of glutathione S-transferase placental form positive foci as an end point after 6 weeks of promotion.

• Archives of Pharmacal Research
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• v.22 no.2
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• pp.99-107
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• 1999

A series of organosulfur compounds were synthesized with the aim of developing chemopreventive compounds active against hepatotoxicity and chemical carcinogesis. 2-(Allylthio) prazine (2-AP) was effective in inhibiting cytochrome P450 2E1-mediated catalytic activities and protein expression, and in inducing microsomal epoxide hydrolase and major glutathione S-transferases. 2-AP reduced the hepatotoxicity caused by toxicant sand elevated cellular GSH content. Development of skin tumors, pulmonary adenoma and aberrant crypt foci in colon by various chemical carcinogens was inhibited by 2-AP pretreatment. Anticarcinogenic effects of 2-AP at the stage of initiation of tumors were also observed in the aflatoxin B1 ($AFB_1$)-induced three-step medium-term hepatocarcinogenesis model. Reduction of $AFB_1$-DNA adduct by 2-AP appeared to result from the decreased formation of $AFB_1$-8,9-epoxide via suppression of cytochrome P450, while induction of GST 2-AP increases the excretion of glutathione-conjugated $AFB_1$ . 2-AP was a radioprotective agent effective against the lethal dose of total body irradiation and reduced radiation-induced injury in association with the elevation of detoxifying gene expression. 2-AP produces reactive oxygen species in vivo, which is not mediated with the thiol-dependent production of oxidants and that NF-KB activation is not involved in the induction of the detoxifying enzymes. the mechanism of chemoprotection by 2-AP may involve inhibition of the P450-mediated metabolic activation of chemical carcinogens and enhancement of electrophilic detoxification through induction of phase II detoxification enzymes which would facilitate the clearance of activated metabolites through conjugation reaction.