Pharmacology and Toxicology / Operative and Restorative Dentistry (Reichl)

Department / Institute
Walther-Straub-Institute of Pharmacology and Toxicology, LMU,
Department of Operative/Restorative Dentistry, Periodontology and Pedodontics
Project title
China Scholarship Council,
Ludwig Maximilians University Munich, Joint Program
Univ.-Prof. Dr. Dr. Franz-Xaver Reichl
Walther-Straub-Institute of Pharmacology and Toxicology, LMU
and Department of Operative/Restorative Dentistry, Periodontology and Pedodontics,
LMU Nussbaumstr. 26
D-80336 Munich
Tel.: +49/89/2180/73842
Fax: +49/89/2180/73841

Project description

(Co)Monomers (e.g. triethyleneglycoldimethacrylate (TEGDMA), hydroxyethylmethacrylate (HEMA), or Bis-phenolglycidyldimethacrylate (BisGMA)) are commonly used constituents of resin-based dental materials (e.g. composites). Upon placement, light-cured dental polymers may release a wide spectrum of compounds due to incomplete monomer-conversion during polymerization. Unpolymerized (co)monomers can be released, e.g. from composites, and can diffuse into the tooth pulp or the gingiva. They can also reach the gingiva and organs by the circulating blood after the uptake from swallowed saliva. In previous experiments we demonstrated the formation of toxic intermediates in the metabolism of these (co)monomers in the organism. Furthermore we demonstrated genotoxic potentials of some dental composite components. Scarce information is available about time dependent cytotoxic and mutagenic/cancerogenic effects of (co)monomers and moreover for the detected toxic dental intermediates derived from (co)monomers.

In this project the cytotoxic and mutagenic/cancerogenic effects of (co)monomers and metabolic intermediates should be investigated on human oral cells (e.g. gingival cells). Time dependent cytotoxicity should be tested by exposure of substances at various time intervals.

In order to test the hypothesis that released dental restorative materials and/or dental intermediates can reach toxic levels in human oral tissues, cytotoxicity of these substances should be investigated using: (1) the modified XTT-test and (2) the lactate dehydrogenase (LDH) assay. Cell proliferation and viability should be determined by means of a colorimetric XTT-based assay, as has been previously described. The LDH test is a suitable and established test for determining the quantity of LDH enzyme released from the damaged cells as has been also previously described.

The mutagenic/cancerogenic effects of dental (co)monomers and dental intermediates should be investigated using the Gamma-H2AX-assay. In this test-system the immunohistochemical coloring of the phosphorylated histone H2AX is a significant marker of DNA double-strand breaks in cells, caused by xenobiotics and/or other physical factors (e.g. radiation). For these experiments the confocal laser scanning microscope (brand new in the munich dental clinic) can be used for the detection of the phosphorylated and fluorescence colored (FITC) H2AX histones. The marked histones can be seen as red bright spots in the cell nucleus.

At the end of these toxicological investigations a health dose risc assessment may be given for people wearing composites and/or other dental restorative materials.

Duration for the total project: 4 years.

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