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Genotoxic and mutagenic potential of camphorquinone in L5178/TK(+/-) mouse lymphoma cells

 
: Volk, Joachim; Ziemann, Christina; Leyhausen, Gabriele; Geurtsen, Werner

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Dental materials 34 (2018), No.3, pp.519-530
ISSN: 0109-5641
ISSN: 1879-0097
English
Journal Article
Fraunhofer ITEM ()
Camphorquinone; mouse lymphoma cells; oxidative stress; mutagenicity

Abstract
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 (0.25-2.5mM). 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.
RESULTS: CQ (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.
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.

: http://publica.fraunhofer.de/documents/N-497559.html