Induction of metabolic activating enzymes by bisphenol A derivatives or phtalic esters and effects of calcium
Project/Area Number |
17592036
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
補綴理工系歯学
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Research Institution | Health Sciences University of Hokkaido |
Principal Investigator |
HIKAGE Sakari Health Sciences University of Hokkaido, School of Dentistry, Associate Professor, 歯学部, 助教授 (20134710)
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Project Period (FY) |
2005 – 2006
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Project Status |
Completed (Fiscal Year 2006)
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Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
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Keywords | Cytochrome P450 (CYP) 1A1 / CYP1A1 gene induction / Bisphenol A / Phthalic esters / Polymerase chain reaction (PCR) / Aryl hydrocarbon Receptor (AhR) / Luciferase assay / Intracellular calcium / フタル酸工ステル / Polymerase chain reaction(PCR) / Aryl hydrocarbon Receptor(AhR) / WY-14643 / Cytochrome P450 / 遺伝子導入細胞 / レポータージーンアッセイ / プラスミド / HepG2細胞 |
Research Abstract |
Among the families of carcinogen activating enzyme (cytochrome P450), CYP3A is one of the major forms of the human cytochrome P450 (CYP) in human livers. Bisphenol A (BPA) and phthalic esters derivatives are contained in some dental materials. We investigated the cytotoxic effects of the dental resin monomer after being metabolized by P450 (CYP3A4and CYP3A7). It is concluded that P450 (CYP3A4 and CYP3A7) do not activate Bis-GMA and Bis-MEPP resin monomer. It is also confirmed that Bis-GMA and Bis-MEPP act neither as the activator nor as the inhibitor of these P450 enzymes, therefore, it exhibited no cytotoxic effects tested in this study. Moreover, HepG2 cells, an established cell line of epithelial cells derived from a human liver cancer, that were transfected with the human CYP1A1 promoter-luciferase chimeric gene. We showed that BPA derivatives in combination with 3-methylcholanthrene (3-MC) superinduce the human CYP1A1 gene using HepG2 cells. The phthalic esters did not induce the human CYP1A1 gene. However, the phthalic esters together with MC superinduced the human CYP1A1 gene. It was suggested that BPA and di (2-ethylhexyl) phthalate (DEHP) involve with inhibition of the ubiquitous endoplasmic reticulum Ca-ATPases and increase of intracellular calcium concentration. Moreover, it was suggested that BPA induces aryl hydrocarbon receptor (AhR) mRNA.
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Report
(3 results)
Research Products
(5 results)
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[Journal Article] Supreinduction of cytochrome P450 1A1 by di (2-ethylhexyl)ethylhexyl)phthalate,2006
Author(s)
S.Hikage, N.Shibahara, S.Iwao, T.Saito, T.Kamataki, N.Saeada, T Hongo
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Journal Title
84^<th> International Association for Dental Research (Brisbane), Abstract : J Dent Res, #0958 85, Special Issue B (CD-ROM)
Related Report
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