• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.100-105
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• 2002

• 환경생물
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• 제22권1호
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• pp.177-183
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• 2004

유기주석화합물인 tributyltin chloride (TBTC), tributyltin oxide (TBTO)와 triphenyltin chloride (TPTC)를 넙치 간장으로 만든 미크로좀에 in vitro적으로 노출시켜서 이들 화합물의 대사에 관여하는 mixed function oxidase (MFO) 중 cytochrome P450 (CYP) 농도와 7-ethoxyresorufin deethylase (EROD) 활성의 변화를 조사하였으며, 또한 in vivo 실험에서는 TPTC를 넙치에게 복강주사(7.5 mg $kg^{-1}$ BW)하여 간장의 MFO (CYP농도, NADPH cytochrome c 환원효소 활성, NADH chtochrome b5 환원 효소 활성, EROD 활성) 반응을 경시적으로 조사하였다. 그 결과, in vitro에서는 TBTC, TBTO 및 TPTC가 모두 CYP 농도와 EROD 활성을 저해하였으며, 저해력은 TPTC가 가장 컸고 이어서 TBTO, TBTC의 순이었다. 유기주석화합물의 노출농도와 노출시간과 비례하면서 저해정도가 커졌으며, 특히 EROD활성의 저해는 노출농도에 크게 의존적이었다. 그리고 in vivo실험에서도 유기주석 화합물은 CYP농도, NADPH cytochrome c 환원효소 활성, NADH cytochrome b5 환원효소 활성, EROD 활성을 억제하였다. EROD 활성은 오염물질에 의한 반응이 민감하고 재현성도 있어 바람직한 측정지표로 이용될 수가 있을 것이다.

• 환경생물
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• 제22권1호
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• pp.171-176
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• 2004

비이온성 계면활성제로 많이 쓰이는 알킬페놀류의 하나인 노닐페놀(nonylphenol)이 해산어류에게 미치는 영향을 조사하려고 주요 양식어종인 조피볼락에게 복강주사로 10 및 25 mg $kg^{-1}$을 1회 투여하였다. 한편 용제인 DMSO만을 주사한 sham구를 설정하여 비교하였다. 주사 후 7일간 간중량지수(hepatosomatic index)의 변화를 조사하였고, 또한 간장 미크로좀 중 대표적인 약물대사효소인 cytochrome P450 (CYP) 농도와 ethoxyresorufin deethylase (EROD) 활성의 변화도 측정하였다. 그 결과, 고농도(25 mg $kg^{-1}$) 주사구에서는 HSl가 감소하였는데, 이것은 NP가 간장에 독성이 있다는 것을 보여준다. 한편, 약물대사효소 중 CYP 농도는 유도되었지만 EROD 활성은 저해되는 경향을 보였다. 이번에 주사한 농도는 우리나라 연근해 해수 중의 NP 농도에 비해 매우 높은 수준이지만, 본 실험에서는 NP가 조피볼락에 게간장 독성을 보였고, 간장의 약물대사효소에도 영향을 미친다는 것을 확인할 수 있었다.

• BMB Reports
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• 제39권4호
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• pp.448-451
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• 2006

Chemopreventive and cytotoxic effect of genistein against human breast cancer cell lines was investigated. Genistein inhibited cell proliferation in estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) human breast carcinoma cell lines. Cytochrome P450 (CYP) 1A1-mediated ethoxyresorufin O-deethylase (EROD) activity was inhibited by genistein in a concentrationdependent manner. Genistein significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cyclooxy-genase-2 activity and protein expression at the concentrations of 10 (p < 0.05), 25 (p < 0.05) and 50 mM (p < 0.01). In addition, ornithine decarboxylase (ODC) activity was reduced to 53.8 % of the control after 6 h treatment with 50 mM genistein in MCF-7 breast cancer cells. These results suggest that genistein could be of therapeutic value in preventing human breast cancer.

• Journal of Microbiology and Biotechnology
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• 제16권9호
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• pp.1405-1409
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• 2006

Polysaccharides from the starfish Asterina pectinifera were assessed in vitro for their chemopreventive potential in human breast cancer. The polysaccharides from A. pectinifera inhibited cell proliferation in the estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) human breast carcinoma cell lines. In addition, the polysaccharides were found to be an inhibitor of cytochrome P450 1A1-mediated ethoxyresorufin O-deethylase activity, and caused a dose-dependent inhibition of aromatase activity in microsomes isolated from a human placenta. There was a significant reduction in the ornithine decarboxylase activity to 30.7% of the control in the polysaccharide-treated MCF-7 breast cancer cells. Therefore, the polysaccharides from A. pectinifera merit further investigation with respect to breast cancer chemoprevention.

• 한국수산과학회지
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• 제34권3호
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• pp.194-198
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• 2001

PCBs의 경구 투여에 의한 틸라피아, Oreochromis niloticus의 간 cytochrome P450 효소계의 변화를 30일간 관찰하였다. 30일 동안 PCBs 0.05, 0.25 및 0.50mg/kg을 투여했을 때, HSI는 각각 1.81, 1.72 및 $1.54\%$ 감소하였으나, 유의한 차이는 인정되지 않았다. PCBs 0.05mg/kg에 노출된 간 cytochrome P450 농도는 30일째 대조구에 비해 1.4배 유의한 증가를 나타냈고, 0.25mg/kg 이상에서는 실험 20일 이후부터 유의적으로 증가하였다. EROD 활성도는 PCBs 0.05 mg/kg에서 실험 30일째부터 유의하게 증가하여 약 8배 높게 나타났다. 또한, PCBs 0.25mg/kg이상에서는 실험 20일째부터 유의하게 증가하여 30일째부터는 각각 18 및 22배의 증가를 나타냈다. PROD는 PCBs $0.05\~0.50mg/kg$에 노출시킨 개체에서 $0.78\~1.93$pmole/mg protein이 측정되어 대조구에 비해 뚜렷한 변화는 관찰되지 않았다. 이상의 결과는 자연 수역에서 PCBs의 잔류에 따라 먹이를 통해 틸라피아의 체내에 적어도 0.05 mg/kg 이상이 30일간 이상 계속적으로 유입될 경우에 간 cytochrome P450농도 및 EROD 활성도는 증가될 것으로 추정된다.

• 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.112.2-112.2
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• 2003

CYP1 enzymes, CYP1A1, CYP1A2 and CYP1B1, are known to bioactivate procarcinogens particularly polyaromatic compounds. Flavonoids are a class of natural compounds that are present in edible plants. Structurally, these compounds are polyphenols with two aromatic rings (A, B) and a heterocycyclic ring (C). We observed the differential inhibition of 5,7-dihydroxyflavones which are different in numbers of B-ring-OH, to the activity of ethoxyresorufin O-deethylase (EROD) in human hepatic microsomes with the IC50 values, ie, 0.57 mM, 1.28 mM, and 3.62 mM, chrysin, apigenin, and Luteolin, respectively. (omitted)

• Archives of Pharmacal Research
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• 제28권10호
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• pp.1114-1121
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• 2005

Flavonoids are polyphenols composed of two aromatic rings (A, B) and a heterocyclic ring (C). In order to determine the effects of the number of hydroxyl groups in the B-ring of the flavonoids on human cytochrome P450 (CYP) 1 family enzymes, we evaluated the inhibition of CYP1A-dependent 7-ethoxyresorufin O-deethylation activity by chrysin, apigenin and luteolin, using bacterial membranes that co-express human CYP1A1, CYP1A2, or CYP1B1 with human NADPH-cytochrome P450 reductase. Chrysin, which possesses no hydroxyl groups in its B-ring, exhibited the most pronounced inhibitory effects on CYP1A2-dependent EROD activity, followed by apigenin and luteolin. On the contrary, CYP1A1-mediated EROD activity was most potently inhibited by luteolin, which is characterized by two hydroxyl groups in its B-ring, followed by apigenin and chrysin. However, all of the 5,7-dihydroxyflavones were determined to similarly inhibit CYP1B1 activity. Chrysin, apigenin, and luteolin exhibited a mixed-type mode of inhibition with regard to CYP1A2, CYP1B1, and CYP1A1, with apparent Ki values of 2.4, 0.5, and 2.0 ${\mu}M$, respectively. These findings suggested that the number of hydroxyl groups in the B-ring of 5,7-dihydroxyflavone might have some influence on the degree to which CYP1A enzymes were inhibited, but not on the degree to which CYP1B1 enzymes were inhibited.

• Toxicological Research
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• 제9권2호
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• pp.177-186
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• 1993

Previous results from several laboratories have demonstrated that tumor necrosis factor-alpha (TNFalpha) depressed cytochrome P-450 (P-450)-dependent drug metabolism in vivo. However, there is some debate whether the action of TNFalpha is mediated by its direct effects on hepatocytes, or is indirectly mediated through the release of other mediators like IL-1 from macrophages. In the present studies, we investigated the effects of TNFalpha on P-450-dependent drug metabolizing enzyme as measured by 7-ethoxyresorufin O-deethylase (EROD) activity.

• 한국연초학회지
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• 제20권1호
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• pp.99-107
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• 1998

Numerous studies have demonstrated a negative association between cigarette smoking and Parkinson's disease. The present study was undertaken to investigate whether chronic exposure of mice to cigarette smoke a(footed the metabolism of 1-methyl-1113,6-tetrahydro-pyridine (MPTP) by cytochrome P4SO (P-450) or flavin-containing monooxygenase (FMO) in the hepatic microsomes of C57BL6/J mice. Adult male C57BL6/J mice were exposed to mainstream smoke generated from 15 cigarettes for 10 min a day and 5 day per week for 6 weeks. MPTP (10 mg/kg body weight) was administered to mice by subcutaneous injection for 6 consecutive days. Microsolnal P-450 content was increased by MPTP, smoke exposure, or both, but NADPH cytochrome P-450 reductase activity was rather decreased by the same treatments. The activities of benzo(a)pyrene hydroxylase, 7-ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase were significantly increased by the exposure of cigarette smoke, but were not or little affected by MPTP treatment. Benzphetamine N-demethylase activity was not affected either by MPTP treatment or by cigarette smoke exposure, but it was significantly increased by the combined MPTP treatment with cigarette smoke exposure, showing their synergic effect for the induction of the enzyme activity. Interestingly, in vitro studies of hepatic FMO and P-450 system both O-oxygenation and N-demethylation of MPTP were increased in the smoke-exposed or in the MPTP-treated mice. These results suggest that the enhancement in the N-demethylation as well as O-deethylation of P-450 system and in the N-oxygenation of FMO activity by cigarette smoke exposure in mouse liver may contribute to attenuating the neurotoxic effects of MPTP on the nigrostriatal dopaminergic neurons.