Polychlorinated biphenyl quinone-induced genotoxicity, oxidative DNA damage and γ-H2AX formation in HepG2 cells

Chem Biol Interact. 2014 Apr 5:212:47-55. doi: 10.1016/j.cbi.2014.01.016. Epub 2014 Feb 3.

Abstract

Our previous study has demonstrated that PCB quinone is cytotoxic in HepG2 cells (Toxicology in Vitro 26 (2012) 841-848). However, it is not clear whether PCB quinone is also carcinogenic (or mutagenic). In the current study, we investigated the genotoxicity of PCB quinone (2,3,5-trichloro-6-phenyl-[1,4]benzoquinone, PCB29-pQ) in HepG2 cells using single cell gel electrophoresis (SCGE) assay and micronucleus (MN) assay. We found PCB29-pQ exposure significantly increased olive tail moment (OTM) and micronuclei (MN) frequencies in HepG2 cells. These data suggested that PCB29-pQ caused DNA strand breaks and chromosome breaks. We further investigated whether the genotoxicity of PCB29-pQ is associated with the generation of reactive oxygen species (ROS). Using enzyme-linked immunosorbent assay for 8-hydroxydeoxyguanosine (8-OHdG) detection, we demonstrated that the level of oxidative DNA damage was significantly evaluated with PCB29-pQ exposure concentration and time dependently. Moreover, γ-H2AX appeared after the treatment of PCB29-pQ in HepG2 cells, may indicate double strand breaks (DSBs). In addition, the pretreatment of ROS scavengers inhibited the genotoxicity of PCB29-pQ significantly. In conclusion, our data suggested that PCB29-pQ causes genotoxic effects in HepG2 cells, probably via ROS-induced oxidative DNA damage.

Keywords: Genotoxicity; Oxidative stress; PCB; Quinone; ROS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoquinones / toxicity*
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • DNA Damage*
  • Endpoint Determination
  • Free Radical Scavengers / pharmacology
  • Hep G2 Cells
  • Histones / biosynthesis*
  • Histones / metabolism
  • Humans
  • Mutagens / toxicity*
  • Oxidative Stress / drug effects*
  • Oxidative Stress / genetics*
  • Phosphorylation / drug effects
  • Polychlorinated Biphenyls / toxicity*
  • Reactive Oxygen Species / metabolism

Substances

  • Benzoquinones
  • Free Radical Scavengers
  • H2AX protein, human
  • Histones
  • Mutagens
  • Reactive Oxygen Species
  • quinone
  • Polychlorinated Biphenyls