• Toxicological Research
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• 제32권2호
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• pp.89-93
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• 2016

Human cytochrome P450 enzymes (P450s, CYPs) are major oxidative catalysts that metabolize various xenobiotic and endogenous compounds. Many carcinogens induce cancer only after metabolic activation and P450 enzymes play an important role in this phenomenon. P450 1B1 mediates bioactivation of many procarcinogenic chemicals and carcinogenic estrogen. It catalyzes the oxidation reaction of polycyclic aromatic carbons, heterocyclic and aromatic amines, and the 4-hydroxylation reaction of $17{\beta}$-estradiol. Enhanced expression of P450 1B1 promotes cancer cell proliferation and metastasis. There are at least 25 polymorphic variants of P450 1B1 and some of these have been reported to be associated with eye diseases. In addition, P450 1B1 polymorphisms can greatly affect the metabolic activation of many procarcinogenic compounds. It is necessary to understand the relationship between metabolic activation of such substances and P450 1B1 polymorphisms in order to develop rational strategies for the prevention of its toxic effect on human health.

• Journal of Nutrition and Health
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• 제23권1호
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• pp.11-18
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• 1990

Sprague-dawley 숫쥐를 식이지방을 달리하여(I:Soybean oil p/s 4.0, II:beef tallow p/s 0.08) 이유후 8주동안 사육하였다. 이때 I,II군은 각각 기초식이군, 기초식이군에 0.3% butylated hydroxytoluene(BHT)를 첨가신킨 군, 생후 5~7주 사이에 4번의 2-Acetylaminofluorene(2-AAF)를 투여한 군 2-AAF를 투여하고 BHT도 먹인 군으로 나누었다. BHT는 이유 후부터 식이에 섞어 먹였으며 2-AAF를 투여하지 않은 군읜 2-AAF 주사에 의해 얻는 stress와 같은 효과를 주기위해 placebo로 polyethylene glycol 300을 투여하였다. Mixed function oxidase(MFO)계의 효소인 cytochrome p-450, cytochrome b$_5$및 cytochrome p-450 reductase와 과산화지질 등을 측정하였다. 성장기에 2-AAF의 투여는 성장지연을 초래하였으며 지질과산화물은 지방의종류, 2-AAF,BHT 등에 의해 큰 차는 없었다. Cytochrome p-450은 2-AAF에 의해 I-BHT-AAF와 II-AAF군에서 증가되었고 BHT에 의해서는 차이가 나지 않았다. 불포화지방을 먹인경우 cytochrome p-450과 cytochrome p-450 reductase가 2-AAF에 의해 증가되기보다는 오히려 감소하거나 I,II군에 비해 별 차이가 없었는데 2-AAF의 농도와 식이의 불포화도가 높아 세포막이 손상되었기 때문이라 사료된다. Cytochrome $b_5$는 각군 사이에 별 차가 없었다. Cytochrome p-450과 과산화지질(r=0.2475, p<0.05), cytochrome p-450 reductase와 cytochrome $b_5$ (r=0.2475, P<0.05)가 각각 양의 상관관계를 나타내었다. 따라서 2-AAF를 대사시키는 MFO계는 식이지방의 종류 및 BHT의 존재에 따라 영향을 받고, 특히 불포화지방식이인 경우 2-AAF를 대사시킬 수 있는 cytochrome p-450 유도 및 합성능력이 매우 저조함을 알 수 있으며 2-AAF는 어린 쥐의 성장을 지연시켰다.

• Toxicological Research
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• 제13권4호
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• pp.385-391
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• 1997

Inductive effects of cytochrome P450 2B1 by $\alpha$- and $\beta$-ionone were characterized in individual liver lobes of male Sprague Dawley rats. When rats were administered ionones orally at 100, 300, and 600 mg/kg for 24 hr, cytochrome P450 2B1 was induced dose-dependently in liver S-9 fractions as measured by P450 2B-specific monooxygenases and Western immunoblotting. The activity of P450 1A- and P450 2B-specific monooxygenases was differentially expressed in each lobe of normal liver. In addition, the monooxygenase activity was induced by $\alpha$- and $\beta$-ionone with different potency in each lobe of the liver. Our present results indicate that the different induction of P450s by $\alpha$- and $\beta$-ionone in each lobe may explain different susceptibilities of rat liver lobes to certain hepatotoxicants which require metabolic activation for their toxicity and that $\alpha$- and $\beta$-ionone may be useful model inducers of P450 2B1 in studying the toxic mechanism of certain toxicants which may require the metabolic activation by P450.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.148.2-149
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• 2003

Recently we have reported that various hydroxystilbenes show strong inhibition of human cytochrome P450 1 enzyme activities. A series of syntheic trans-stilbene derivatives were prepared and their inhibitory potentials were evaluated with the bacterial membrane of recombinant human cytochrome P450 1A1, 1A2 and 1B1 coexpressed with hyman NADPH-P450 reductase to find a new inhibitor of cytochrome P450 enzymes. Of the compounds tested, SY-081 exhibited a potent inhibition of human cytochrome P450 1B1 with an $IC_50$ value of 2.6 nM. (omitted)

• Archives of Pharmacal Research
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• 제27권2호
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• pp.199-205
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• 2004

Cytochrome P450 (P450) 1 enzymes such as P450 1A1, 1A2, and 181 are known to be involved in the oxidative metabolism of various procarcinogens and are regarded as important target enzymes for cancer chemoprevention. Previously, several hydroxystilbene compounds were reported to inhibit P450 1 enzymes and were rated as candidate chemopreventive agents. In this study, we investigated the inhibitory effect of 2-[2-(3,5-dimethoxyphenyl)vinyl]-thiophene (DMPVT), produced from the chemical modification of oxyresveratrol, on the activities of P450 1 enzymes. The inhibitory potential by DMPVT on the P450 1 enzyme activity was evaluated with the Escherichia coli membranes of the recombinant human cytochrome P450 1A1, 1A2, or 1B1 coexpressed with human NADPH-P450 reductase. DMPVT significantly inhibited ethoxyresorufin O-deethylation (EROD) activities with $IC_{50}$ values of 61, 11, and 2 nM for 1A1, 1A2, and 1B1, respectively. The EROO activity in OMBA-treated rat lung microsomes was also significantly inhibited by OMPVT in a dose-dependent manner. The modes of inhibition by DMPVT were non-competitive for all three P450 enzymes. The inhibition of P450 1B1-mediated EROD activity by OMPVT did not show the irreversible mechanism-based effect. The loss of EROD activity in P450 1B1 with OMPVT incubation was not blocked by treatment with the trapping agents such as glutathione, N-acetylcysteine, or dithiothreitol. Taken together, the results suggested DMPVT to be a strong noncompetitive inhibitor of human P450 1 enzymes that should be considered as a good candidate for a cancer chemopreventive agent in humans.

• Toxicological Research
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• 제11권2호
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• pp.205-213
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• 1995

This study was undertaken to investigate the effects of organic solvents on xenobiotic metabollzing enzyme system in vivo by meaas of experimental conditions i.e. (1) single group which was treated by benzene (B), toluene (T) and xylene (X), respectively, (2) combination group which was treated by mixture of benzene+toluene (BT), benzene+xylene (BX), and toluene+xylene (TX), respectively, (3) mixture group which was treated by benzene+ toluene+xylene mixture (M), and to interpreat the interaction between the organic solvents metabolizing enzymes. 1. The contents of cytochrome P-450 in liver microsomes were increased (p < 0.01) in organic solvents treated groups, and the contents of cytochrome P-450 were increased by following order of B < T < M < BT=BX < X < TX. 2. The activity of cytochrome P-450 dependent AHHase was significantly higher in organic solvents treated groups than in control group (p < 0.01), and the activity of AHHase was increased by following order of B < T < BT=BX=TX=xylene < M. 3. The activity of NADPH P-450 reductase was significantly higher in organic solvents treated groups than in control group (p < 0.01), and the order of M < combinated group < X < T

• 대한의생명과학회지
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• 제1권1호
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• pp.89-94
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• 1995

B(a)P와 cytochrome P-450의 heme부분은 구조가 평면이므로 겹침 상호작용이 가능하다. 가능성이 큰 겹침 상호작용모형을 결정하기 위해 이들 분자에 대해 MO계산을 행하였다. 이 경우 궤도함수 상호작용이 가장 중요하므로, 프론티어궤도함수의 eigen vetor값이 크며 상호 결합성을 보여야 한다. 이를 바탕으로 다섯가지 가능성이 있는 모형을 선택한 수 MN2와 MO방법을 실행하였다. 이중 B(a)P의 4, 5, 6번 위치와 heme group의 Y탄소와 III pyrrole환이 포개어지는 형태가 가장 안전하였다.

• Applied Biological Chemistry
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• 제38권2호
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• pp.168-173
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• 1995

Endosulfan이 흰쥐(Balb/c.) 체내의 cytochrome P-450 효소계에 미치는 영향을 조사하기 위해 endosulfan을 7.5 mg/kg 수준으로 복강주사하였다. Endosulfan을 복강주사 처리하여 48시간 후 적출한 흰쥐의 간에서는 cytochrome P-450 함량이 $3.3{\sim}4.2$배, cytochrome $b_5$ 함량이 $2.3{\sim}3.8$배, NADPH cytochrome P-450 reductase 활성이 $5.3{\sim}6.4$배 그리고 총 haem 함량이 $3.1{\sim}3.6$배씩 대조구의 그것들에 비해 증가하였다. Endosulfan은 대조구 흰쥐 간의 cytochrome P-450 효소계와 상호작용하여 파장 387와 389 nm에서 흡광도의 증가를 보였으며 파장 407 nm에서 넓은 흡수대를 형성하였다. 환원형 P-450-CO spectrum은 대조구의 경우 파장 451 nm에서 흡광도의 극대를 보인 반면 endosulfan으로 처리된 흰쥐 간의 그것은 파장 449와 450 nm에서 흡광도의 극대를 보였다. Endosulfan 처리로 흰쥐 간과 신장의 aldrin epoxidase 활성이 각각 2.8배와 2.1배씩 증가하였으며 7-ethoxyresorufin dealkylase 활성은 각각 1.7배와 1.8배씩 증가하였다.

• Journal of Microbiology and Biotechnology
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• 제15권1호
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• pp.183-187
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• 2005

Abstract The cancer chemopreventive potential of chitosanoligosaccharides was investigated by measuring the induction of quinone reductase and glutathione S-transferase activities and inhibition of cytochrome P450 1A1, 2B1, and 2E1 activities. Chitosanoligosaccharide I (1-${\kappa}$Da${\kappa}$Da) significantly induced glutathione S-transferase activity with a maximal 1.5-fold increase at 500 ${\mu}$g/ml, while chitosanoligosaccharide II (3-${\kappa}$Da${\kappa}$Da) (500 ${\mu}$g/ml) strongly induced quinone reductase (p<0.01) and glutathione S-transferase (p<0.005) activities. The in vitro incubation of rat liver microsomes with chitosanoligosaccharides I and II (2.5, 5, 50, and 500 ${\mu}$g/ml) showed a dose-dependent inhibiton of cytochrome P450 1A1, 2B1, and 2E1 activities. Chitosanoligosaccharide II was a more potent inhibitor of cytochrome P450 2B1 activity than chitosanoligosaccharide I. Accordingly, these findings suggest that chitosanoligosaccharides are potential chemopreventive agents.

• 한국균학회지
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• 제31권1호
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• pp.34-39
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• 2003

싸리버섯 메탄올 추출물이 간독성 물질인 B$({\alpha})$P을 투여한 마우스에서 간 손상 억제 효과 및 cytochrome P-450 1A1 발현에 미치는 영향을 살펴보았다. B$({\alpha})$P 투여로 인한 혈청 ALT와 AST의 활성, 간 조직증의 lipid peroxide 함량, cytochrome P-450 함량, AD 및 AH 활성이 유의적으로 증가하였으며 싸리버섯 메탄올 추출물의 투여시 이들 활성 및 함량이 유의적으로 감소하였다. 반면, 간 조직중의 GSH 함량, GST, r-glutamylcysteine synthetase의 활성은 B$({\alpha})$P만 투여한 군에 비해 싸리버섯 메탄올 추출물을 투여시 증가하였다. 또한 immuno blotting 결과로부터 B$({\alpha})$P 투여에 의해 현저히 증가되었던 cytochrome P-450 1A1 isozyme 단백질 함량이 싸리버섯 메탄올 추출물의 투여로 감소됨을 확인하였다. 이와 같은 결과로부터 싸리버섯 메탄올 추출물은 B$({\alpha})$P에 의한 간 손상에 대한 보호 효과가 있는 것으로 사료된다.