• Archives of Pharmacal Research
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• v.21 no.3
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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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• v.32 no.2
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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.

• Korean journal of applied entomology
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• v.32 no.3
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• pp.291-299
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• 1993

Midgut tissues from 4 insect specIes were exammed for the activity of cytochrome P-450 monooxygenases, a major enzyme involved in chemical detoxification. When Helicoverpa assulta larvae were reared on an artificial d;et, the specific activity of the midgut cytochrome P-450 monooxygenases (MFO) was :3 times higher than that of the fat body, The specific activity of the midgut cytochrome P-450 monooxygenases was higher in H. assul/a larvae when reared on Nicotiana tabacum leaves than when on CapsIcum annuum fruits or an artificial diet. In the case of Hyphantria cunea larvae, Tilia megaphyllo leaves were the best in inducing midgut cytochrome P-450 monooxygenases activity. When larvae of H. assulta, Spodoptera exigua, H. cunea and Spodoptera litura were reared on their own artificial diet, the highest activity was seen in S. exigua larvae which is a polyphagous and insecticide-resistant strain.

• Proceedings of the Korea Society of Environmental Biology Conference
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• 2001.12a
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• pp.105-106
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• 2001

• Korean Journal of Plant Resources
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• v.24 no.5
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• pp.584-590
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• 2011

Wound inducible P450-Esg cDNA, one of cytochrome P450 gene family, was isolated from shoot of Euiseong garlic cultivar. P450-Esg cDNA possesses highly conserved heme-binding domain in the nucleotide sequence, and 1,419 bp of open reading frame (ORF) coding of 473 amino acids. Based on the nucleotide sequence analysis of P450-Esg homologous from twelve garlic cultivars, two domains, one domain between 472 to 510 bp, and the other between 1,210 to 1,249 bp from start codon (ATG), showed various nucleotide polymorphism among cultivars. Sequence of heme-binding domain in P450-Esg homologous, which is located at the domain between 1,210 to 1,240 bp from start codon, showed various nucleotide polymorphism as well as amino acid sequence polymorphism among twelve garlic cultivars. Anther domain, between 472 to 510 bp from start codon, showed exactly same amino acid sequence in the twelve garlic cultivars, but there were various single nucleotide polymorphism to the cultivars.

• Environmental Analysis Health and Toxicology
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• v.17 no.4
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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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• v.29 no.7
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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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• v.14 no.2
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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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• v.23 no.3
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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.

• The Journal of Internal Korean Medicine
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• v.34 no.4
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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.