• Archives of Pharmacal Research
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• 제21권3호
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• pp.305-309
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• 1998

Human cytochrome P450 1A2 is one of the major cytochrome P450s in human liver. It is known to be capable of activating a number of carcinogens such as arylamines and heterocyclic amines. In order to develop the new bacterial mutagenicity test system with human P450, a full length of human P450 1A2 cDNA inserted into pCW bacterial expression vector was introduced to Escherichia coli WP2 uvrA strain which is a well-known E. coli strain for bacterial reverse mutagenicity assay. Expressed human P450 1A2 showed typical P450 hemoprotein spectra. Maximum expression was achieved at 48 hrs after incubating at $30^{\circ}C$ in terrific broth containing ampicillin, IPTG and other supplements. High level expression of P450 1A2 in E. coli WP2 uvrA membranes was determined in SDS-PAGE. The well-known mutagens 2-aminoanthracene and MElQ increased the revertant colonies of E. coli WP2 uvrA expressing human P450 1A2 without an exogenous rat hepatic post-mitochondrial supernatant (S9 fraction) in a dose-dependent manner. The results show that the functional expression of human P450 in bacterial mutagenicity tester strain will provide a useful tool for studying the mechanism of the mutagenesis and carcinogenesis of new drugs and environmental chemicals.

• 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.

• 한국응용곤충학회지
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• 제32권3호
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• pp.291-299
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• 1993

네가지 종류의 곤충 중장에 있는 주요 해독효소인 cytochrome P-450 monooxygenases의 활성을 그들의 먹이종류 및 섭식여부와 연관시켜 분석하였다. 담배나방유충을 인공사료로 사육하였을 때 전반적으로 중장의 cytochrome P-450 monooxygtenases(MFO)활성이 지방체의 경우보다 3배가량 높게 나타났다. 고추열매나 인공사료를 공급하여 사육하였을 때보다 담배잎으로 사육하였을 때 담배나방유충의 중장 MFO는 훨씬 높게 나타났으며, 흰불나방의 경우염주나무잎이 MFO활성을 가장 높게 유기했다. 담배나방, 파밤나방, 희불나방, 담배거세미나방 등의 유충들을 각각의 인공사료로 사육하였을 때 광식성이며 동시에 살충제저항성을 보유하고 있는 파밤나방의 MFO활성이 가장 높게 나타났다.

• 한국환경생물학회:학술대회논문집
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• 한국환경생물학회 2001년도 학술대회
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• pp.105-106
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• 2001

• 한국자원식물학회지
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• 제24권5호
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• pp.584-590
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• 2011

의성종 마늘의 유묘로부터 상처(wound)에 특이적으로 발현되는 cytochrome P450 유전자군의 하나인 P450-Esg cDNA를 탐색하였다. P450-Esg는 1,419 bp의 open reading frame(ORF)을 가지고 473개의 아미노산을 가진 polypeptide를 코딩하는 것으로 나타났다. 국내와 몽골로부터 수집한 12개의 재배종으로 부터 P450-Esg 유사 유전자의 염기서열을 비교한 결과 시작코돈(ATG)에서 472~510 bp 및 1,210~1,240 bp 부위의 염기에서 재배종간에 차이를 보이는 염기서열을 다수 확인하였다. cDNA 1,210~1,240 bp의 부위는 P450 유전자에서 공통적으로 알려진 heme binding domain으로, 각 지역에서 수집된 재배종은 염기서열뿐만 아니라 아미노산 서열에 있어서도 특이적인 변이를 보였다. cDNA 472~510 bp 부위에서 코딩하는 13개 아미노산의 서열은 12개 재배종에서 모두 동일하였으나, 13개 아미노산 중 7개에서 재배종 마다 각각 다른 DNA 염기로 코딩하는 단일 염기다형성(single nucleotide polymorphism)을 보이는 서열을 확인하였다. 이 결과는 다양하게 존재하는 국내외 마늘 재배종을 구분하는 marker로 사용될 것이며, 외국산 마늘에 대한 유전적 우선권을 확보하는 수단으로 사용될 것이다.

• Environmental Analysis Health and Toxicology
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• 제17권4호
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• pp.307-314
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• 2002

Effects of ($\pm$)-camphor on liver cytochrome P450 enzymes were investigated in male ICR mice. Mice were treated intraperitoneally with 0, 200, 400 and 800 mg/kg of ($\pm$)-camphor in corn oil for 3 consecutive days. Twenty four hr after the final treatment, the animals were subjected to necropsy. The activities of serum aspartate aminotransferase and serum alanine aminotransferase were slightly changed by the treatment with ($\pm$)-camphor at the doses used. Administration of ($\pm$)-camphor to mice significantly induced the hepatic activities of pentoxyresorufin O-depentylase and benzyloxyresorufin O-debenzylase and weakly induced ethoxyresorufin O-deethylase in dose-dependent manners. The present results suggested that ($\pm$)-camphor might act as a relatively specific inducer of hepatic cytochrome P450 2B in male ICR mice.

• Journal of Nutrition and Health
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• 제29권7호
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• pp.689-702
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• 1996

The purpose of this experiment was to compare the effects of tryptophan administration on nutritional status of female rats which consumed reserpine and 6% casein diet with different carbohydrate contents(87%, 65%, 44% respective). Final body weight, body weight gain, FER, plasma amino acid concentration and microsomal cytochrome P 450 content in liver were measured and microscopic structure of hepatocytes was observed. In low-protein diet, the higher the carbohydrate content of diet was, the lower the damage was in the rat's liver. Tryptophan administration after dose of reserpine induced more effective recovery from liver damage of rats in high carbohydrate diet group than that in low carbohydrate diet group. In conclusion, the general nutritional assessments such as final body weight and body weight gain provided better estimate of the degree of structural changes in hepatocytes than functional assessment such as plasma amino acid concentration or liver microsomal cytochrome P450.

• Archives of Pharmacal Research
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• 제14권2호
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• pp.130-136
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• 1991

Nicotine (100 .mu. M) was incubated with microsomes (1 mg/ml) prepared from New Zealand White rabbits. On the basis of microsomal weight, the rate of nicotine oxidation were calculated on the basis of cytochrome P-450 concentration, the specific activity of the metabolic oxidation catalyzed by lung was approximately 4 times greater than liver (6.4 vs 1, 65 nmoles nicotine oxidized. nmole cytochrome $P-450^{-1}\;min{-1})$. These studies employed several methods of altering activities of specific isozymes present in pulmonary microsomes, including the use of the isozyme2 and 6 specific inhibitor $\alpha$-methylbenzyl ABT, metabolite inhibitors, norbenzphetamine and N-hydroxyamphetamine. TCDD induction and Arochlor 1260 pretreatment. These results support the conclusion that nicotine metabolism by rabbit lung microsomes is mediated primarily by cytochrome P-450 isozyme 2.

• Toxicological Research
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• 제23권3호
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• pp.189-196
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• 2007

Cytochrome P450 (P450) enzymes are the major catalysts involved in the biotransformation of various drugs, pollutants, carcinogens, and many endogenous compounds. Most of chemical carcinogens are not active by themselves but they require metabolic activation. P450 isozymes playa pivotal role in the metabolic activation. The activation of arylamines and heterocyclic arylamines (HAAs) involves critical N-hydroxylation, usually by P450. CYP1A2 plays an important role in these reactions. Broad exposure to many of these compounds might cause carcinogenicity in animals and humans. On the other hand, P450s can be also involved in the bioactivation of other chemicals including alcohols, aflatoxin B1, acetaminophen, and trichloroethylene, both in humans and in experimental animals. Understanding the P450 metabolic activation of many chemicals is necessary to develop rational strategies for prevention of their toxicities in human health. An important part is the issues of extrapolation between species in predicting risks and variation of P450 enzyme activities in humans.

• 대한한방내과학회지
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• 제34권4호
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• pp.375-383
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• 2013

Objectives : This study was performed to investigate the metabolic site of some medicinal herbs in the liver associated with CYP (Cytochrome P450). Methods : Cytochrome P450 is the major enzymes involved in drug metabolism and bioactivation. CYP3A4 and CYP2D6, the major CYP isoforms in humans, catalyse the major proportion of drugs available on the market. Scintillation proximity assay (SPA) is often used in studies to identify compounds that inhibit CYP3A4 and CYP2D6. 28 herbal extracts and radioisotopes were attached competitively to SPA beads, and followed by measuring the remaining radioisotopes in the medium. Erythromycin and dexamethasone, inhibitors of CYP3A4 and CYP2D6, were used as controls respectively. Results : Most of the 28 herbal extracts showed dose-dependent affinity to the CYP3A4 while some of the herbs showed affinity to the CYP2D6. Conclusions : These results suggest that most of the 28 herbal extracts are metabolized safely in the liver, combined with CYP3A4 and CYP2D6.