• Environmental Mutagens and Carcinogens
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• v.24 no.3
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• pp.143-150
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• 2004

In mammalian, cytochrome P4501A1 (CYP1A1) is very important for metabolism of xenobiotics such as PAHs(Polycyclic aromatic hydrocarbon) and heterocyclic amine, and it is induced by environmental contaminants such as PAHs, TCDD(2,3,7,8-tetrchlorodibenzo-p-dioxin) and 3-MC (3-methylcholanthrene). In fish, like mammalian, when it is exposed to environmental contaminants, they cause specific and sensitive induction of CYP1A. Therefore, induction of CYP1A in fish and mammalian is widely used as a biomarker for exposure of environmental contaminants. In this study, to compare the function of Cyp1a1 in fish with it in mammalian, we have used rainbow trout(Oncorhynchys mykiss) hepatoma cells (RTH-149) and mouse hepatocyte (Hepa-I). in order to examine induction of Cyp1a1 by TCDD, we have used the bioassay system. We examined effects of TCDD on the Cyp1a1-luciferase reporter gene activity, 7-ethoxyresorufin O-deethylase(EROD) activity and Cypa mRNA level.

• Radiation Oncology Journal
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• v.22 no.3
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• pp.217-224
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• 2004

Purpose: It is well known that the radiosensitivity of tumor cells can be significantly reduced under hypoxic conditions. Hypoxia-inducible factor-1 $\alpha$ (HIF-1 $\alpha$) plays a pivotal role in the essential adaptive responses to hypoxia. Therefore this study investigated the relationship between HIF-1 $\alpha$ expression and radiosensitivity. M Mouse hepatoma cell line hepafcic7 and HIF-1 $\beta$-deficient mutant cell line hepa1C4 were used to analyze the role of HIF-1 a. on radiosensitivity. These cells were exposed for 6 h to desferrioxamine (DFX) before radiation. HIF-1$\alpha$. expression was examined by Western blot. Apoptosis was assessed by DNA fragmentation, propidium iodide staining, and apoptotic cell death detection ELISA kit. Radiation sensitivity was determined using MTT assay. The radiobioiogical parameters, surviving fractions at 2 Gy and 8 Gy, and mean inactivation dose (MID) from the linear-quadratic model were used to assess radiation sensitivity in the statistical analyses. Results: The expression of HIF-1 $\alpha$. was Increased, whereas apoptosis was decreased, by radiation In the presence of DFX In hepal cl c7, but not In hepal C4. The radlosensitivity of hepal C4 cells was not significantly affected by DFX treatment. The radiosensitivlty of hepal cl c7 cells was significantly decreased in the presence of DFX Conclusion: The expression of HIF-1 w by hypoxia-mimic agent DFX reduced apoptosls and radiosensitlvity in mouse hepatoma cell line hepafclc7. These results suggested that HIF-1 u could be Induced by irradiation in hypoxic ceils of tumor masses, and that this mlght Increase radioresistance in hypoxic cells.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.152-152
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• 2002

In order to understand the mechanism of action of TCDD, we have examined the effect of COX-inhibitors on cyplal activity. We observed the effect of COX-inhibitor on EROD activity in C57BL/6 mouse in vivo. And we also evaluated the effect of COX-inhibitors on cyplal mRNA, mouse cyp1a1 promoter activity and EROD activity in Hepa cell.(omitted)

• Korean Journal of Pharmacognosy
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• v.32 no.2 s.125
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• pp.168-174
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• 2001

Induction of phase II enzymes is a major mechanism of chemoprevention. The induction levels of quinone reductase (QR) activity in cultured murine hepatoma (Hepa 1c1c7) cells by 80%-methanol extracts of traditional medicinal plants were measured. Among the tested 81 plants, the extracts of Aralia continentalis, Magnolia obovata, and Viscum album were found to induce QR activities over 250%. The maximum induction levels obtained were 401.9%, 270.5%, and 301.8% by treatments of the extracts of A. continentalis $(318\;{\mu}g/ml)$, M. obovata $(53.8\;{\mu}g/ml)$ and V. album $(80.6\;{\mu}g/ml)$, respectively. These QR induction activities were more potent than those of the known QR inducers, t-butylhydroquinone (170.1%) and ${\beta}-naphthoflavone$ (320.0%).

• Biomolecules & Therapeutics
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• v.20 no.5
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• pp.487-491
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• 2012

The aim of this study was to investigate the inhibitory effects of rutaecarpine on DNA strand breaks and apoptosis induced by hydrogen peroxide ($H_2O_2$) in murine Hepa-1c1c7 cells. Oxidative DNA damage was estimated by nuclear condensation assessment, fluorescence-activated cell sorting analysis, and Comet assay. Rutaecarpine inhibited cell death induced by $500{\mu}M$ $H_2O_2$, as assessed by 4',6-diamidino-2-phenylindole (DAPI) staining. Treatment with rutaecarpine reduced the number of DNA strand breaks induced by $H_2O_2$, as assessed by DAPI staining and Comet assay, and increased quinone reductase, phosphatidylinositol 3-kinase, and pAkt protein levels, as assessed by western blotting.

• Environmental Mutagens and Carcinogens
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• v.24 no.4
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• pp.171-179
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• 2004

Cytochrome P4503A4(CYP3A4) is the most abundnat CYPs in human liver, comparising approximately 30% of the total liver CYPs contents ans is involbed in the metabolism of more than 60% of currently used therapeutic drugs. The expression of CYP3A4 is induced by a variety of structurally unrelated xonobiotics including the antibiotic rifampicin and endogenous hormones, and might be mediated through steroid and xenobiotic receptor(SXR) system. The molecular mechanisms underlying regulation of CYP3A4 gene expression hae not been understood. In order to gain the insight of the molecular mechanism of CYP3A4 gene expression, study has been undertaken to investigate if the histone deacelylation is involved in the regulation of CYP3A4 gene expression by proximal promoter or not. Also SXR was investigated to see if they were involved in the regulation of CYP3A4 proximal promoter activity. HepG2 or Hena-I cells were transfected with a plasmid containing~1kb of the CYP3A4 proximal promoter region (-863 to +64bp) cloned in front of a reporter gene, luciferase, in the presence or absence of SXR or hER. Transfected cells were treated with CYP3A4 inducers such as rifampicin, PCN and RU 486, or with estradiol, in order to exmine to regulation of CYP3A4 gene expression in the presence or absence of trichostatin A (TSA). In HepG2 cells, CYP3A4 inducers and estradiol increased significantly the luciferase activity by CYP3A4 proximal promoter, only when TSA was co-treated after SXR cotransfection. In the case of Hepa-I cells CYP3A4 inducers and estradiol incressed modestly the luciferase activity when TSA was co-treated, but this increment was not enhanced by SXR cotransfection in contrast to HepG2 cells. Taken together, these results indicated that the inhibition of histone deacetylation was required to SXR-mediated increase in CYP3A4 proximal promoter region when rifampicin, or PCN was treated. Futher a trans-activation by SXR may demand other species-specific transcription factors.

• Korean Journal of Acupuncture
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• v.17 no.1
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• pp.11-17
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• 2000

Induction of phase II enzymes such as quinone reductase (QR) or glutathione S-transferase (GST) is considered a major mechanism of protection against initiation of carcingenesis. The induction of detoxification enzymes and glutathione were studied with Lonicerae Flos aqua-acupuncture solution (LFAS), Angelicae gigantis Radix aqua-acupuncture solution (AGRAS), and Gamdutang aqua-acupunture solution (GAS) in murine hepatoma cells grown in microtiter plate wells. LFAS, AGRAS and GAS were potent inducers of QR activity. LFAS was induced about 2.6-fold at concentration of $3{\times}$. AGRAS and GAS were also induced about 2.6-, 1.8-fold at concentration of $5{\times}$, respectively. In addition, GST activity was increased with LFAS, AGRAS, and GAS. GSH levels were increased about 2-fold with LFAS at concentration of $5{\times}$, 1.3-fold with AGRAS at concentration of $3{\times}$, and 1.2-fold with GAS at concentration of $5{\times}$. These results suggested that LFAS, AGRAS, and GAS may act as blocking agents against carcinogenesis by induction of phase II marker enzymes.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2002.10a
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• pp.173-173
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• 2002

In order to understand the mechanism of action of TCDD, we have examined the effect of COX-inhibitors on cyp1a1 activity. We observed the effect of COX-inhibitor on EROD activity in C57BL/6 mouse in vovo. And we also evaluated the effect of COX-inhibitors on cyp1a1 mRNA, mouse cyp1a1 promoter activity and EROD activity in Hepa cell. When Aspirin were pretreated with 3MC in vivo, the EROD activity that was stimulated by 3MC was inhibited. And Pretreatment of Aspirin, Celecoxib, Nimesulide and other several Cox-inhibitors in vitro, inhibited the TCDD stimulated EROD activity and Luciferase acitivity. In case of cyp1a1 mRNA level, Nimesulide and SB100 were able to decrease cyp1a1 mRNA that was stimulated by TCDD, but other tested COX-inhibitors were not decrease. We don't know this different result exactly. For the action of Cox-inhibitors on the Cyp1a1, it seems to be important to do pretreatment of these chemicals as apposed to TCDD. In this study, thus, we have suggested that COX-inhibitors such as aspirin, celecoxib, Nimesulide and other several Cox-inhibitors decrease the TCDD induced Cyp1a1.

• Proceedings of the Korean Society of Toxicology Conference
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• 2005.05a
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• pp.170-170
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• 2005

• Proceedings of the Zoological Society Korea Conference
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• 2001.10a
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• pp.261.1-261
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• 2001

No Abstract, See Full Text