Genotoxic and mutagenic potential of camphorquinone in L5178/TK+/− mouse lymphoma cells

Publication date: Available online 17 January 2018
Source:Dental Materials
Author(s): J. Volk, C. Ziemann, G. Leyhausen, W. Geurtsen
ObjectivesCamphorquinone (CQ) is the most important photoinitiator used in dental composite resins. Sparse data indicate a mutagenic potential of CQ. Therefore, it was aim of this study to evaluate the cytotoxicity, genotoxicity, and mutagenicity of CQ in L5178Y TK^+/− mouse lymphoma cells.MethodsL5178Y/TK^+/− cells were exposed to different concentrations of non-irradiated CQ (0.25–2.5mM). Cytotoxicity was evaluated by propidium iodide assay, determination of suspension growth rate, relative total growth and the mitotic index. Intracellular levels of reactive oxygen/nitrogen species (ROS/RNS) were quantified by 2′,7′-dichlorofluoresceine diacetate (DCFH-DA). Early induction of DNA strand breaks and oxidative DNA base lesions was assessed using the 8-hydroxyguanine DNA-glycosylase 1 (hOGG1)-modified alkaline comet assay, whereas mutagenicity of CQ was determined in the mouse lymphoma TK assay (MLA), according to OECD Guideline No. 490.ResultsCQ (0.5–2.5mM) induced concentration- and time-dependent inhibition of cell growth associated with increased ROS/RNS production, amounting to 2342%±1108% of controls after 90min at 2.5mM. Additionally, CQ concentration-dependently caused direct DNA-damage, i.e. formation of DNA strand breaks and 8-hydroxy-2′-deoxyguanosine. Whereas the MLA indicated lack of mutagenicity of CQ after a 4h of treatment, CQ concentration-dependently increased total mutant frequency (MF) after 24h (about 2-fold at 2.5mM). But, based on the global evaluation factor concept, increase in MF did not reach biologically relevance.SignificanceCQ induced concentration-dependent, cytotoxic and genotoxic effects in L5178Y/TK^+/− cells, most likely due to oxidative stress, but without mediating obvious biological relevant mutagenicity.



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