• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.11a
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• pp.159-159
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• 2004

• Development and Reproduction
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• v.11 no.3
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• pp.187-193
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• 2007

Ethane 1,2-dimethane sulfonate(EDS), a Leydig cell specific toxicant, has been widely used to create the reversible testosterone withdrawal rat model. Though the maintenance of epididymal structure and function is highly dependent on the testosterone secreted from testis, its derivatives, dihydroxytestosterone(DHT) and estrogen, might have crucial roles. The aim of present study was to monitor the expression patterns of sex steroid receptors, cytochrome P450 aromatase(P450arom) and $5{\alpha}$-reductase in the rat epididymis up to 7 weeks after EDS injection. Adult male rats($350{\sim}400g$) were injected with a single does of EDS(75 mg/kg i.p.) and sacrificed on weeks 0, 1, 2, 3, 4, 5, 6 and 7. The transcriptional activities of the target genes were evaluated by semi-quantitative RT-PCRs. The transcript level of estrogen receptor alpha($ER{\alpha}$) in EDS group was significantly higher than control level on week 1(P<0.01). After week 2, there was no significant difference in $ER{\alpha}$ levels between EDS group and control. The transcript level of estrogen receptor beta($ER{\beta}$) in EDS group was significantly higher than control level on week 1(P<0.05), lowered on weeks 2 and 3(P<0.05 and P<0.01, respectively), fluctuated during weeks 4 and 6, and elevated on week 7(P<0.05). The androgen receptor (AR) message levels increased significantly week 2(P<0.01), then returned to control level on week 3. In contrast, expression of cytochrome P450 aromatase(P450arom) decreased sharply during weeks $1{\sim}3$(P<0.01 on weeks 1 and 2; P<0.05 on week 3), then went back to control level on week 4. The mRNA level of $5{\alpha}$-reductase type 2($5{\alpha}$-RT2) increased significantly on week 4(P<0.01), then returned to control level. The present study indicated that EDS administration could induce reversible alterations in the transcriptional activities of sex steroid hormone receptors and androgenconverting enzymes in rat epididymis. EDS injection model will be useful to clarify the regulation mechanism of mammalian epididymal physiology.

• 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 ]

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.10a
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• pp.153-155
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• 1995

To investigate the mechanism of the regulation of cytochrome P450IAl, the 5'-flanking region of a trout cytochrome P4501Al was cloned into the CAT basic expression vector at HindⅢ site. This trout Cytochrome P450IAl upstream DNA containing CAT construct was transfected into Hepa-1 cells .3MC treatment to hepa I cells transfected with trout P450IAl-CAT construct increased CAT protein and mRNA by 2.81 fold when it was compared with that of control. This increase CAT protein and mRNA was decreased by concomitantly treated flavonoids and aminopyrine. The level of CAT protein was 29.2-58.0% of 3MC stimulated CAT protein.

• Korean Journal of Pharmacognosy
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• v.34 no.4 s.135
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• pp.297-302
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• 2003

Cnidii Rhizoma water extract (CRW) was tested for liver cancer chemopreventive potential by measuring the inhibition of phase I enzyme and benzo[a]pyrene-DNA adduct formation and induction of phase II detoxification enzymes. There was 17.0% inhibition in the activity of cytochrome P450 1A1 enzyme with the treatment of 150 mg/ml CRW. At concentration of 30 mg/ml CRW, the binding of $[^3H]B[a]P$ metablites to DNA of NCTC-clone 1469 cell was inhibited by 33.3%. CRW was potent inducer of quinone reductase (QR) and glutathione S-transferase (GST) activities in cultured murine hepatoma Hepalc1c7 cells. However, hepatic glutathione (GSH) level was not influenced by CRW. These findings suggest that CRW has chemopreventive potential of liver cancer by inhibiting cytochrome P450 1A1 activity and benzo[a]pyrene-DNA adduct formation and inducing QR and GST activities.

• YAKHAK HOEJI
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• v.31 no.6
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• pp.361-369
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• 1987

The four azo dyes such as Amaranth (FD & C Red No. 2), Tartrazine (FD & C Yellow No. 4), sunset Yellow (FD & C Yellow No. 5) and Allura red (FD & C Red No. 40) are currently employed as a food additives in Korea. In this study, the effects of these azo dyes on the hepatic microsomal mixed function oxidase systems in Rats. (i.e., Cyt. P-450, Cyt. b$_5$, NADPH cyt. c-reductase and azo reductase) were investigated. Furthermore, to determine the relationship among the electron transport systems, each level of azo reductase, Cyt. P-450 and NADPH cyt. c-reductase was measured upon the administration of phenobarbital (known as an inducer of Cyt. P-450), 3-methylcholanthrene (Known as an inducer of Cyt. P-448), CoCl$_2$ (inhibitor on Cyt. P-450) or $CCl_4$ (inhibitor on Cyt. P-450). The results of these studies are as follows; (1) The levels of Cyt. P-450 and Cyt. b$_5$ were decreased upon the administration of these azo dyes. (2) When the level of Cyt. P-450 was decreased, the azo reductase activity was also decreased. (3) These azo dyes did not show any significant effect on the level of NADPH cyt. c-reductase. (4) The administration of 3-methylcholanthrene resulted in the elevation of azo reductase activity. The 3-methylcholanthrene may be responsible for the induction of CO-insensitive electron transport system.

• BMB Reports
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• v.32 no.3
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• pp.226-231
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• 1999

In vitro effects of acetone on cytochrome P450 (P450)-dependent benzo(a)pyrene (B(a)P) hydroxylation supported by cumene hydroperoxide (CuOOH) or NADPH/$O_2 $ systems were studied using 3-methylcholanthrene-pretreated rat liver microsomes. The maximal rate of B(a)P hydroxylation at constant concentration ($80\;{\mu}M)$ of the substrate was observed in the presence of $30\;{\mu}M$ CuOOH. However, at concentrations higher than $30\;{\mu}M$ CuOOH the hydroxylation rates were rapidly decreased. In contrast to CuOOH, at a concentration of $200\;{\mu}M$ NADPH, B(a)P hydroxylation rate reached a plateau. At concentrations higher than $200\;{\mu}M$ NADPH, the rates of substrate hydroxylation were maintained at the maximal rate with no inhibition. Acetone at 1% (v/v) enhanced both CuOOH- and NADPH/$O_2$-supported B(a)P hydroxylation at the optimal concentrations of the cofactors. At concentrations higher than 1% (v/v) acetone, substrate hydroxylation was sterero specific under the support of these two cofactors; it was strongly enhanced with $30\;{\mu}M$ CuOOH, but rather inhibited in the $200\;{\mu}M$> NADPH/$0_2 $ system. The lipid peroxidation rate induced during CuOOH-supported P450-dependent B(a)P hydroxylation was increased as CuOOH concentrations were increased. Acetone in the concentration range of 2.5~7.5%(v/v) inhibited lipid peroxidation during CuOOH supported B(a)P hydroxylation. The finding that CuOOH-supported B(a)P hydroxylation is greatly enhanced by acetone suggests that acetone may contribute more to the activation of oxygen (for the insertion of oxygen into the substrate) in the presence of CuOOH than with NADPH/$O_2$. Acetone may also contribute to the partial inhibition of destruction of microsomal membranes by lipid peroxidation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.10
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• pp.1347-1352
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• 2009

The effects of methanol extract of barely (Hordeum vulgare) on alcohol-induced damages of liver were investigated in male ICR mice. Mice were divided into three groups, control, ethanol, and ethanol plus 0.15% of barley extract. After four weeks of ethanol feeding, ethanol group significantly increased the P450 content, CYP2E1 and CYP1A2 enzyme activities, whereas ethanol plus barely group markedly decreased to levels similar to control group. Catalase activity in ethanol group was significantly lower than that in control group; however, ethanol plus barely group stimulated catalase activity as well as SOD activity significantly. These results indicated that barely extract modulated P450 enzymes for ethanol-induced liver damage and might be useful in developing functional food for alcoholic liver damage.

• Journal of Microbiology and Biotechnology
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• v.13 no.4
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• pp.624-627
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• 2003

Benzo[a]pyrene (B[a]P) is an environmental pollutant that has been implicated in carcinogenesis. Saccharomyces cerevisiae was treated with B[a]P, and the responses of its cytochrome P450 (CYP) enzyme and DNA-damage checkpoint genes were examined through gene expression profiles using a reverse transcription polymerase chain reaction (RT-PCR). The DNA-damage checkpoint genes tested were the chk1 and pds1 genes, involved in a metaphase arrest, the swi6 gene targeted by G1 arrest, the pol2 gene related to S phase arrest, and the cln2 gene encoding a cyclin protein, all of which are based on rad9 and rad24. Among these genes, no noticeable effect was found when the cells were exposed to various concentrations of B[a]P. However, the transcriptional activity of CYP51 was significantly different when the cells were exposed to B[a]P. Accordingly, the present results indicate that cytochrome P450 plays a more significant role than DNA-damage checkpoint genes in the response of S. cerevisiae to B[a]P.

• Environmental Analysis Health and Toxicology
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• v.24 no.3
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• pp.213-218
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• 2009

1-bromopropane (1-BP) has been used in numerous purposes such as an intermediate in the synthesis of pharmaceuticals, a solvent for fats, waxes, or resins and a substitute for chlorofluorocarbons that destroy the ozone layer. However, the studies related to the modulation of activities of hepatic cytochrome P450s (CYPs) are not reported yet. This study was the first study to investigate the potential effect for the activities of hepatic CYPs by the treatment of 1-BP in vivo. When 1-BP was treated to male ICR mice by dose-dependently at the dose levels of 200, 500 and 1,000 mg/kg of body weight once, the activity of CYP2E1 was selectively increased for 24 h. The inductive potency for the activity of CYP2E1 by 1-BP was equal to induction by acetone a well-known selective CYP2E1 inducer. The present results indicated that 1-BP would affect the metabolism of 1-BP itself and/or other xenobiotics.