Genotoxic and mutagenic potential of camphorquinone in L5178/TK^sup +/-^ mouse lymphoma cells

Objectives Camphorquinone (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. Methods L5178Y/TK+/− cells were exposed to different concentrations of non-irradiated CQ (0.25–2.5 mM). 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. Results CQ (0.5–2.5 mM) induced concentration- and time-dependent inhibition of cell growth associated with increased ROS/RNS production, amounting to 2342% ± 1108% of controls after 90 min at 2.5 mM. 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 4 h of treatment, CQ concentration-dependently increased total mutant frequency (MF) after 24 h (about 2-fold at 2.5 mM). But, based on the global evaluation factor concept, increase in MF did not reach biologically relevance. Significance CQ induced concentration-dependent, cytotoxic and genotoxic effects in L5178Y/TK+/− cells, most likely due to oxidative stress, but without mediating obvious biological relevant mutagenicity.