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Reichl, F.X.* ; Seiss, M.* ; Buters, J. ; Behrendt, H. ; Hickel, R.* ; Durner, J.

Expression of CYP450-2E1 and formation of 2,3-epoxymethacrylic acid (2,3-EMA) in human oral cells exposed to dental materials.

Dent. Mater. 26, 1151-1156 (2010)

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Open Access Green as soon as Postprint is submitted to ZB.

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Objectives. Methacrylate-based (co)monomers released from dental composites can be, metabolized in vivo to methacrylic acid (MA). MA can be further oxidized to the toxic 2,3-epoxymethacrylic acid (2,3-EMA) by cytochrome P450 (CYP450) enzymes. The subform CYP450-2E1, can metabolize xenobiotics with low-molecular weight to epoxides. Oral cells are highly exposed to (co) monomers released from composites. Therefore in this study the, expression of CYP450-2E1 in human oral (and other) cells was investigated as well as the formation of 2,3-EMA in cells exposed to MA. Methods. Following human oral cells were used: human gingiva fibroblasts (HGF), human pulp fibroblasts (HPF), and human tumor buccal keratinocytes (SqCC/Y1). As negative control V79 cells without CYP450-2E1 expression were used. As positive controls V79 cells with CYP450-2E1 expression (V79-CYP450-2E1) and pooled human liver microsomes were used. The expression of CYP450-2E1 in cells was analyzed with the real-time polymerase chain reaction (RT-PCR). 2,3-EMA was quantified by the use of the method of gas chromatography/mass spectrometry (GC/MS). Results. The highest expression of CYP450-2E1 was found in human liver microsomes, followed by SqCC/Y1 cells, V79-CYP450-2E1 cells, HGF, and HPF. The highest amount of 2,3-EMA (mu mol/L; mean +/- SEM, n = 3) was found in human liver microsomes (5.0 +/- 1.0), followed by SqCC/Y1 cells (2.5 +/- 0.8), V79-CYP450-2E1 cells (1.5 +/- 0.6), HPF (0.3 +/- 0.3), and HGF (0.2 +/- 0.2). Significance. It is concluded that the formation of the toxic epoxide 2,3-EMA, as intermediate in the metabolism of dental materials, can occur also in human oral cells which can express the CYP450-2E1 enzyme system.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords RESTORATIVE MATERIALS; CYTOCHROME-P450 2E1; GUINEA-PIGS; METABOLISM; RISK; TOXICOKINETICS; IDENTIFICATION; MICROSOMES; ALCOHOL; CYP2E1

ISSN (print) / ISBN 0109-5641

e-ISSN 0109-5641

Journal Dental Materials

Quellenangaben Volume: 26, Issue: 12, Pages: 1151-1156

Publisher Elsevier

Publishing Place Oxford

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) CCG Environmental Dermatology and Allergology (ILBD-KAU)
Institute of Epidemiology (EPI)