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.

中文翻译：

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樟脑醌在L5178 / TK ^+/-小鼠淋巴瘤细胞中的遗传毒性和诱变潜力

目标

樟脑醌（CQ）是在牙科复合树脂中使用的最重要的光引发剂。稀疏数据表明CQ具有诱变潜力。因此，本研究的目的是评估C5在L5178Y TK ^+/-小鼠淋巴瘤细胞中的细胞毒性，基因毒性和诱变性。

方法

L5178Y / TK ^+/-细胞暴露于不同浓度的未辐照CQ（0.25–2.5 mM）。通过碘化丙啶测定，悬浮液生长速率，相对总生长和有丝分裂指数的测定来评估细胞毒性。细胞内活性氧/氮物质（ROS / RNS）的水平通过2'，7'-二氯荧光素二乙酸盐（DCFH-DA）进行定量。根据OECD，使用8-羟基鸟嘌呤DNA-糖基化酶1（hOGG1）修饰的碱性彗星测定法评估了DNA链断裂和DNA氧化碱基损伤的早期诱导，而CQ的致突变性是在小鼠淋巴瘤TK测定法（MLA）中确定的准则号490。

结果

CQ（0.5–2.5 mM）诱导浓度和时间依赖性的细胞生长抑制与ROS / RNS产生增加有关，在2.5 mM的90分钟后达到对照组的2342％±1108％。另外，CQ浓度依赖性地直接引起DNA损伤，即形成DNA链断裂和8-hydroxy-2'-deoxyguanosine。尽管MLA表明治疗4小时后CQ缺乏致突变性，但CQ浓度依赖于24小时后总突变频率（MF）的增加（在2.5 mM时约为2倍）。但是，基于全球评估因素的概念，MF的增加并未达到生物学相关性。

意义

CQ在L5178Y / TK ^+/-细胞中诱导浓度依赖性，细胞毒性和遗传毒性作用，最可能是由于氧化应激，但没有介导明显的生物学相关诱变性。