Evaluation of genotoxic potential of tert-butylquinone and its derivatives in prokaryotic and eukaryotic test models

Drug Chem Toxicol. 2020 Sep;43(5):522-530. doi: 10.1080/01480545.2018.1514043. Epub 2018 Sep 27.

Abstract

Tert-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/umuC assay in Salmonella typhimurium 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.

Keywords: SOS/umuC; Tert-butylquinone; alkylamino and aralkylamino derivatives; comet assay; genotoxicity; plasmid relaxation.

MeSH terms

  • Benzoquinones / toxicity*
  • Cells, Cultured
  • Comet Assay
  • DNA Damage*
  • Hep G2 Cells
  • Humans
  • Plasmids / genetics
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics

Substances

  • Benzoquinones
  • 2-tert-butyl-4-quinone