| Polychlorinated-biphenyl-induced oxidative stress and cytotoxicity can be mitigated by antioxidants after exposure. | |
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MedLine Citation:
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PMID: 19796678 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-09-28 |
Journal Detail:
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Title: Free radical biology & medicine Volume: 47 ISSN: 1873-4596 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-11-16 Completed Date: 2010-01-26 Revised Date: 2013-05-31 |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: United States |
Other Details:
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Languages: eng Pagination: 1762-71 Citation Subset: IM |
Affiliation:
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Free Radical and Radiation Biology Program, B180 Medical Laboratories, Department of Radiation Oncology, Holden Comprehensive Cancer Center, Iowa City, IA 52242, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antioxidants
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pharmacology* Cell Line, Tumor Cell Proliferation / drug effects Environmental Pollutants / antagonists & inhibitors*, toxicity Humans Oxidative Stress / drug effects* Polychlorinated Biphenyls / antagonists & inhibitors*, toxicity Superoxide Dismutase / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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P30 CA-086862/CA/NCI NIH HHS; P30 CA086862-10S46947/CA/NCI NIH HHS; P30 ES-05605/ES/NIEHS NIH HHS; P30 ES005605-190006/ES/NIEHS NIH HHS; P42 ES-013661/ES/NIEHS NIH HHS; P42 ES013661-040002/ES/NIEHS NIH HHS; R01 CA-111365/CA/NCI NIH HHS; R01 CA111365-03/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Environmental Pollutants; 0/Polychlorinated Biphenyls; EC 1.15.1.1/Superoxide Dismutase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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