Polychlorinated-biphenyl-induced oxidative stress and cytotoxicity can be mitigated by antioxidants after exposure

Yueming Zhu, Amanda L. Kalen, Ling Li, Hans J. Lehmler, Larry W. Robertson, Prabhat C. Goswami, Douglas R. Spitz, Nukhet Aykin-Burns*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

PCBs and PCB metabolites have been suggested to cause cytotoxicity by inducing oxidative stress, but the effectiveness of antioxidant intervention after exposure has not been established. Exponentially growing MCF-10A human breast and RWPE-1 human prostate epithelial cells continuously exposed for 5 days to 3 μM PCBs [Aroclor 1254 (Aroclor), PCB153, and the 2-(4-chlorophenyl)-1,4-benzoquinone metabolite of PCB3 (4ClBQ)] were found to exhibit growth inhibition and clonogenic cell killing, with 4ClBQ having the most pronounced effects. These PCBs were also found to increase steady-state levels of intracellular O2·- and H2O2 (as determined by dihydroethidium, MitoSOX red, and 5-(and 6)-carboxy-2′,7′-dichlorodihydrofluorescein diacetate oxidation). These PCBs also caused 1.5- to 5.0-fold increases in MnSOD activity in MCF-10A cells and 2.5- to 5-fold increases in CuZnSOD activity in RWPE-1 cells. Measurement of MitoSOX red oxidation with confocal microscopy coupled with colocalization of MitoTracker green in MCF-10A and RWPE-1 cells supported the hypothesis that PCBs caused increased steady-state levels of O2·- in mitochondria. Finally, treatment with either N-acetylcysteine (NAC) or the combination of polyethylene glycol (PEG)-conjugated CuZnSOD and PEG-catalase added 1 h after PCBs significantly protected these cells from PCB toxicity. These results support the hypothesis that exposure of exponentially growing human breast and prostate epithelial cells to PCBs causes increased steady-state levels of intracellular O2·- and H2O2, induction of MnSOD or CuZnSOD activity, and clonogenic cell killing that could be inhibited by a clinically relevant thiol antioxidant, NAC, as well as by catalase and superoxide dismutase after PCB exposure.

Original languageEnglish (US)
Pages (from-to)1762-1771
Number of pages10
JournalFree Radical Biology and Medicine
Volume47
Issue number12
DOIs
StatePublished - Dec 15 2009
Externally publishedYes

Keywords

  • Cytotoxicity
  • Free radicals
  • Mitochondria
  • N-acetylcysteine
  • Oxidative stress
  • PCBs
  • Superoxide dismutase

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Polychlorinated-biphenyl-induced oxidative stress and cytotoxicity can be mitigated by antioxidants after exposure'. Together they form a unique fingerprint.

Cite this