Faculty of Biology, Center for Genotoxicology and Ecogenotoxicology, University of Belgrade, Belgrade, Serbia.
Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia.
Drug Chem Toxicol. 2020 Sep;43(5):522-530. doi: 10.1080/01480545.2018.1514043. Epub 2018 Sep 27.
-butylquinone (TBQ) and its alkylamino and aralkylamino derivatives are of high interest as a potential antitumor agent. Therefore, it was necessary to investigate if the compounds exert undesirable activities such as interaction with DNA molecule which could result in negative side effects in the case of their use in the diseases treatment. The major aim of this study was to investigate genotoxic potential of TBQ and selected derivatives in an acellular model by using plasmid DNA, in the prokaryotic model by the SOS/ assay in TA1535/pSK1002 and in eukaryotic models by using comet assay in human fetal lung cell line (MRC-5) and human liver cancer cell line (HepG2). Results indicated that in the acellular model TBQ and its derivatives do not interact with plasmid pUC19. In the prokaryotic model, only TBQ exerted weak genotoxic potential and only at highly cytotoxic concentrations. In eukaryotic models, genotoxic potential was detected mainly at the highest concentrations of the tested substances but the effect was lower in both cell lines in comparison with benzo[a]pyrene and etoposide which were used as positive controls. Weak genotoxic potential of tested compounds recommends them as good candidates for further testing in development of new antitumor agents.
-丁基醌(TBQ)及其烷基氨基和芳烷基氨基衍生物是一种很有前途的抗肿瘤药物。因此,有必要研究这些化合物是否具有不良活性,如与 DNA 分子相互作用,这可能导致在治疗疾病时产生负面副作用。本研究的主要目的是通过使用质粒 DNA 在非细胞模型中、在 TA1535/pSK1002 的原核模型中通过 SOS/assay 以及在人类胎肺细胞系(MRC-5)和人肝癌细胞系(HepG2)中的彗星试验中研究 TBQ 及其衍生物的遗传毒性潜力。结果表明,在非细胞模型中,TBQ 及其衍生物不与质粒 pUC19 相互作用。在原核模型中,只有 TBQ 表现出较弱的遗传毒性潜力,而且只有在高细胞毒性浓度下才表现出这种潜力。在真核模型中,主要在测试物质的最高浓度下检测到遗传毒性潜力,但与用作阳性对照的苯并[a]芘和依托泊苷相比,在两种细胞系中的作用都较低。测试化合物的弱遗传毒性潜力表明它们是进一步开发新型抗肿瘤药物的良好候选物。