Document Detail

Polychlorinated-biphenyl-induced oxidative stress and cytotoxicity can be mitigated by antioxidants after exposure.
MedLine Citation:
PMID:  19796678     Owner:  NLM     Status:  MEDLINE    
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 microM 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 O(2)(*-) and H(2)O(2) (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 O(2)(*-) 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 O(2)(*-) and H(2)O(2), 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.
Yueming Zhu; Amanda L Kalen; Ling Li; Hans-J Lehmler; Larry W Robertson; Prabhat C Goswami; Douglas R Spitz; Nukhet Aykin-Burns
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-09-28
Journal Detail:
Title:  Free radical biology & medicine     Volume:  47     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-16     Completed Date:  2010-01-26     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1762-71     Citation Subset:  IM    
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MeSH Terms
Antioxidants / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Environmental Pollutants / antagonists & inhibitors*,  toxicity
Oxidative Stress / drug effects*
Polychlorinated Biphenyls / antagonists & inhibitors*,  toxicity
Superoxide Dismutase / metabolism
Grant Support
P30 CA-086862/CA/NCI NIH HHS; P30 CA086862/CA/NCI NIH HHS; P30 CA086862-10S46947/CA/NCI NIH HHS; P30 ES-05605/ES/NIEHS NIH HHS; P30 ES005605/ES/NIEHS NIH HHS; P30 ES005605-190006/ES/NIEHS NIH HHS; P42 ES-013661/ES/NIEHS NIH HHS; P42 ES013661/ES/NIEHS NIH HHS; P42 ES013661-040002/ES/NIEHS NIH HHS; R01 CA-111365/CA/NCI NIH HHS; R01 CA111365/CA/NCI NIH HHS; R01 CA111365-03/CA/NCI NIH HHS
Reg. No./Substance:
0/Antioxidants; 0/Environmental Pollutants; DFC2HB4I0K/Polychlorinated Biphenyls; EC Dismutase

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