• Title/Summary/Keyword: Arylhydrocarbon hydroxylase

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Modulation of Anticarcinogenic Enzyme and Plasma Testosterone Level in Male Mouse Fed Leek-Supplemented Diet (부추 첨가 식이가 수컷 생쥐의 암예방 효소계 및 혈중 웅성호르몬 농도에 미치는 영향)

  • 김정상;곽연주;전희정;이민자;권태완
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.27 no.5
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    • pp.968-972
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    • 1998
  • Allium tuberosum Rotter(Liliaceae) is a perennial herb of which leaves are used for food. Leek has been reported to have pharmacological effects including alleviations of abdominal pain, diarrhea, hematemesis, snakebite, and asthma. To investigate the effect of dietary leek supplementation on the drug-metaboizing enzymes, quinone reductase(QR) and arylhydrocarbon hydroxylase(AHH) activities in the liver, stomach, small intestine and lung, and on the plasma testosterone and dihydrosterone hormone levels, mice were fed 2% and 5% leek diets for 8 weeks. Quinone reductase, an anticarcinogenic enzyme, was significantly induced in stomach, small intestine, and lung but slightly lowered in hepatic tissue in the experimental groups compared to control group. Arylhydrocarbon hydroxylase activity, involved in bioactivation of procarcinogens, was significantly decreased in liver and lung. Leek feeding led to the reduction in the plasma level of dihydrotestosterone which is associated with the incidence of prostate cancer. These findings support the potential chemopreventive activity of leek supplementation.

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Effect of Soybean Supplementation on Murine Drug-metabolizing Enzymes and Benzo(a)pyrene-induced Lung Cancer Develpoment (콩보충식이가 생쥐의 해독효소계 및 Benzo(a)pyrene에 의해서 유도된 폐암발생에 미치는 영향)

  • Kwon, Chong-Suk;Kim, Jong-Sang
    • Korean Journal of Food Science and Technology
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    • v.31 no.2
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    • pp.535-539
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    • 1999
  • Soybean has drawn much attention mainly due to its chemopreventive action as well as antiestrogenic effect. Although suppression of breast and prostate cancers were believed to be exerted via antiestrogenic or antiandrogenic activity of genistein, its mechanism of prevention against other cancers has not been clearly demonstrated. We proposed that prevention by soybean from other cancers than sex hormone -related cancers was achieved via modulation of drug-metabolizing enzymes. Addition of acid hydrolysate of 80% methanol extract of soyflour to diet caused a significant induction of quinone reductase, an anticarcinogenic marker enzyme and one of drug-metabolizing enzymes, in mouse lung while it suppressed arylhydrocarbon hydroxylase, involved in bioactivation of procarcinogens, in kidney and small intestine. It is likely that active components exist in a conjugated form and released by acid hydrolysis to be able to affect drug-metabolizing enzyme and exert chemopreventive activity. Benzo(a)pyrene-induced tumor development in mouse lung was greatly reduced by soybean extract supplementation, which is consistent with the extract's capability to modulate favorably arylhydrocarbon hydroxylase and quinone reductase towards chemoprevention.

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In Vitro Enhancement of Microsomal Cytochrome P450-Dependent Monooxygenases by Organic Solvents in Rat Liver

  • Lee, Dong-Wook;Lim, Heung-Bin;Moon, Ja-Young;Park, Ki-Hyun
    • BMB Reports
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    • v.31 no.4
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    • pp.391-398
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    • 1998
  • In vitro effects of acetone, methanol, and dimethylsulfoxide (DMSO) on liver microsomal cytochrome P450 (P450) content, and P450-dependent arylhydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin O-deethylase (ECOD) activities were studied in rats. Acetone at 1% (v/v) enhanced the content ofP450, assayed spectrally in 3-methylcholanethrene (MC)- and ${\beta}-naphthoflavone$ (BNF)-inducible microsomes by 18 and 7%, respectively. Methanol, up to 5% (v/v) applied, also showed enhancement effects on P450 content in liver microsomes from rats treated with phenobarbital (PB), MC, and BNF, as well as uninduced microsomes with similar but low strength. DMSO, however, did not show such enhancing effects at the ranges of the concentrations applied. AHH and ECOD activities in MC-inducible microsomes were also enhanced by acetone at 1%, which was in proportion to the increase in P450 content by the same concentration. However, the P450 content, and AHH and ECOD activities, were decreased by increasing the concentration of acetone. Methanol at the same concentration with acetone also enhanced ECOD activity but not AHH activity in MCinducible microsomes. The enhancing effect of acetone on the enzymes was negligible when the microsomes were pretreated with a specific monoclonal antibody of MC-inducible isozyme. The difference in the effects of these solvents on P450 system might be due to their different properties that cause the P450 active site to be exposed in milieu.

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Changes in Toxicity of Porphyra tenera Precontaminated with Fluoranthene During Processing (Fluoranthene으로 오염시킨 김의 가공처리중 독성변화)

  • Kim, Jong-Sang;Park, Kwan-Ha;Hwang, In-Young
    • Environmental Analysis Health and Toxicology
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    • v.14 no.3
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    • pp.75-79
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    • 1999
  • Due to increasing marine pollution there is a great possibility that seaweed is contaminated with polycyclic aromatic hydrocarbons (PAHs). To investigate the effect of processing on PAM removal from Porphyra tenera (laver) contaminated PAH, laver was contaminated with fluoranthene known to have a strong photoinduced toxicity, followed by washings and drying, which are usual processes for dried laver preparation. Sample at each step was collected and its toxicity was evaluated using cultured animal cells as well as analyzing PAH contents. Fluoranthene level in laver was significantly lowered by sequential washings with sea water and distilled water, but not by drying. Fluoranthene content in raw laver right after contamination was 221 ppm and decreased to 130 ppm by washings with seawater plus distilled water while its level was not lurker lowered by drying process. Cytotoxicity and photoinduced cytotoxicity in mammalian cells were significantly elevated in laver extracts containing fluoranthene. Cellular arylhydrocarbon hydroxylase (AHH), one of the biomarkers for cellular accumulation of PAH, was greatly induced by laver extract contaminated with fluoranthene. These results suggest that photoinduced toxicity and AHH activity can be used to monitor contamination of seafood by PAHs. Fluoranthene accumulated in laver was efficiently removed by sequential washings with seawater and tap water for 24 hrs and 12 hrs, respectively.

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IN HUMAN BREAST CANCER MCF-7 CELLS, ESTROGEN INVOLVES IN CYPIA1 GENE EXPRESSION.

  • Hwang, J.E.;S.H.Eo;Cho, S.N.;Y.Y.Sheen
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.04a
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    • pp.107-107
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    • 1997
  • Cytochrome P450 enzymes have been intensively investigated in hepatic tissues and several mammalian cell lines. Compared to most studies about cytochrome P450 isozymes in liver in vivo and hepatic, cell lines in vitro, the study of cytochrome P450IA1 in human breast cancer cells could be very important to understand the mechanism of the regulation of CYPIA1 gene expression and cell growth. MCF-7 human breast cancer cells are well characterized to study estrogen and antiestrogen action due to the fact that they contain high level of estrogen receptor and have biological markers characterized. And also MCF-7 cells express high level of arylhydrocarbon hydroxylase activity and human cytochrome P450IA1 cDNA was cloned from MCF-7 cells. Ah receptor was characterized in many breast cancer cell lines and polycyclic aromatic hydrocarbon such as 3-MC induced the expression of CYPIA1 gene and cytochrome P450- dependent monooxygenase activity. We undertook a study to examine the effect of estrogens and other chemicals on the regulation of human CYPIA1 gene expression in MCF-7 cells via RTPCR analysis, that might help us to understand the mechanism of the regulation of CYPIA1 gene expression and MCF-7 cell growth. Expression vector containing the functional 5'-regulatory region of human CYPIA1 fused to the CAT reporter gene was transfected into estrogen receptor positive MCF-T cells or estrogen receptor negative MDA-MB-231 cells. After these cells were treated with various chemicals, RTPCR was carried out to measure both CYPIA1 mRNA and CAT mRNA levels. 1nM 3-MC increased in both P450 and CAT mRNA levels over those of control by two folds in MCF-7 cells but does not in MDA-MB-231 cells. Estrogen or tamoxifen or retinoic acid or chrysin decreased in both P450 and CAT mRNA levels that were induced by 3-MC in MCF-7 when each chemical was administered with 3-MC concomitantly. These results suggested that the level of CYPIA1 gene expression is modulated with estrogen-related molecules and make it possible to speculate that ER is related to CYPIA1 gene expression and cell growth in breast cancer cells. [Supported by grants from the Korean Ministry of Education ]

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