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Camphorquinone induces cytotoxic and genotoxic effects in primary human gingival fibroblasts

 
: Volk, J.; Geurtsen, W.; Leyhausen, G; Günay, H.; Beckedorf, A.; Rahmer, H.; Ziemann, C.

Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie -DGPT-:
48th Spring Meeting 2007. Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie. Abstracts : 13 - 15 March 2007, Mainz, Germany
Berlin: Springer, 2007 (Naunyn-Schmiedeberg's Archives of Pharmacology 375.2007, Suppl. 1)
pp.94
Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie (Spring Meeting) <48, 2007, Mainz>
English
Conference Paper
Fraunhofer ITEM ()
Camphorquinone; cytotoxicity; Genotoxicology; DNA damage

Abstract
Leaching of substances from resin-based dental materials has a potential impact on the biocompatibility as well as safety of these materials. One of the main identified leachables is camphorquinone (CQ). CQ is the most important photoinitiator used in dental adhesives and resin composites. Aim of this study was to evaluate the cytotoxic and genotoxic potential of CQ (0.05 to 2.5mM) on adherent primary human gingival fibroblasts (HGF) in the absence of visiblelight (VL)-irradiation. Cell viability, levels of intracellular reduced glutathione (GSH), and intracellular generation of reactive oxygen species (ROS) were assessed by fluorescence spectroscopic assays, pro-apoptotic effects were evaluated on the level of DNA-fragmentation, and genotoxicity was investigated using the comet assay. During 3h of incubation in the dark CQ induced rapid concentration-dependent formation of ROS in HGF, without reducing cellular viability, even at higher concentrations. The maximum amount of ROS was found at a concentration of 2.5mM CQ, which was equivalent to a ~50-fold increase, as compared to untreated controls. After 24h of incubation, however, CQ concentrations of > 1mM induced a significant reduction in cell number and cell viability with a TC50% of about 2.5mM and 2.3mM CQ, respectively. After an incubation period of 16h with 2.5mM CQ, there was evidence of apoptotic DNA-fragmentation in HGF. Increase of ROS production, observed after 1.5 and 3h of "CQ incubation", was followed in both cases by a marked GSH depletion. The comet assay revealed a significant induction of DNA-damage due to CQ, which was very likely caused by ROS. Therefore, the generation of oxidative DNA-damage and the effects of antioxidants will be further investigated. In conclusion, CQ, even without VL-irradiation, exhibits cytotoxic, genotoxic, and pro-apoptotic potential in primary HGF, which is most likely correlated to ROS generation and a reduced antioxidant capacity of the cells due to GSH depletion.

: http://publica.fraunhofer.de/documents/N-59327.html