Propolis alleviates 4-aminobiphenyl-induced oxidative DNA damage by inhibition of CYP2E1 expression in human liver cells

Environ Toxicol. 2021 Aug;36(8):1504-1513. doi: 10.1002/tox.23147. Epub 2021 Apr 13.

Abstract

4-Aminobiphenyl (4-ABP) may cause DNA damage in human liver cells (HepG2 and L-02). Propolis exhibits antioxidant properties through reactive oxygen species (ROS) scavenging. We determined the effects of propolis in alleviating 4-ABP -induced DNA damage using the comet assay. Results revealed that propolis could significantly alleviated oxidative damaged DNA by 4-ABP. Furthermore, we proved that inhibition of cytochrome P450 2E1 (CYP2E1) expression by propolis could contribute to the decreased oxidative DNA damage in the treated cells, as the conversion of 4-ABP into its metabolite, N-hydroxy-ABP (HOABP), was blocked; after all, HOABP showed more genotoxic than its parent chemical, 4-ABP. With the homologous recombination assay, propolis failed to induce DNA repair enzymes. Furthermore, the expression of RAD51, Ku70/Ku80, and OGG1 in treated cells were determined with the western blot, revealing that the expression of these protein were unchanged in comparison with those in nontreated cells. However, propolis could protect the treated cells from DNA damage. In conclusion, propolis could antagonize 4-ABP-induced oxidative DNA damage though the removal of ROS and inhibition of CYP2E1 expression in the treated cells.

Keywords: 4-ABP; CYP2E1; Ku70/Ku80; OGG1; propolis.

MeSH terms

  • Aminobiphenyl Compounds / pharmacology
  • Carcinogens
  • Cytochrome P-450 CYP2E1* / metabolism
  • DNA Damage
  • Humans
  • Liver
  • Oxidative Stress
  • Propolis* / pharmacology

Substances

  • Aminobiphenyl Compounds
  • Carcinogens
  • 4-biphenylamine
  • Propolis
  • Cytochrome P-450 CYP2E1