Jelena Djordjevic Aleksic , Stoimir Kolarević , Jovana Jovanović Marić , Margareta Kračun-Kolarević , Bojana Žegura , Alja Štern , Dušan Sladić , Irena Novaković , Branka Vuković-Gačić
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引用次数: 0
摘要
本研究的目的是利用无细胞和细胞测试系统，研究叔丁基醌（TBQ）及其烷硫基和芳硫基衍生物对体外 DNA 的影响。使用质粒 pUC19 研究了与 DNA 的直接相互作用。在 HepG2 细胞系中研究了细胞毒性（MTS 试验）和基因毒性（彗星试验和 γH2AX 聚焦试验）效应及其对细胞周期的影响。结果表明，TBQ 及其衍生物不会直接与 DNA 发生作用。2-叔丁基-5,6-（亚乙基二硫）-1,4-苯醌衍生物对 HepG2 细胞的细胞毒性作用最强（处理 24 小时和 48 小时时的 IC50 分别为 64.68 和 55.64 μM）。受试衍生物对暴露细胞群中的细胞周期分布没有明显影响。不过，在彗星试验中，所有衍生物的基因毒性都强于 TBQ，其中 2-叔丁基-5,6-（亚乙基二硫代）-1,4-苯醌的作用最强。在 γH2AX 聚焦试验中，同一种衍生物还能诱导 DNA 双链断裂。
Influence of alkylthio and arylthio derivatives of tert-butylquinone on the induction of DNA damage in a human hepatocellular carcinoma cell line (HepG2)
The aim of this study was to investigate the effects of tert-butylquinone (TBQ) and its alkylthio and arylthio derivatives on DNA in vitro, using acellular and cellular test systems. Direct interaction with DNA was studied using the plasmid pUC19. Cytotoxic (MTS assay) and genotoxic (comet assay and γH2AX focus assays) effects, and their influence on the cell cycle were studied in the HepG2 cell line. Our results show that TBQ and its derivatives did not directly interact with DNA. The strongest cytotoxic effect on the HepG2 cells was observed for the derivative 2-tert-butyl-5,6-(ethylenedithio)-1,4-benzoquinone (IC50 64.68 and 55.64 μM at 24-h and 48-h treatment, respectively). The tested derivatives did not significantly influence the cell cycle distribution in the exposed cellular populations. However, all derivatives showed a genotoxic activity stronger than that of TBQ in the comet assay, with 2-tert-butyl-5,6-(ethylenedithio)-1,4-benzoquinone producing the strongest effect. The same derivative also induced DNA double-strand breaks in the γH2AX focus assay.
期刊介绍：
Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.
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