Document Detail

Catalase ameliorates polychlorinated biphenyl-induced cytotoxicity in nonmalignant human breast epithelial cells.
MedLine Citation:
PMID:  18691649     Owner:  NLM     Status:  MEDLINE    
Polychlorinated biphenyls (PCBs) are environmental chemical contaminants believed to adversely affect cellular processes. We investigated the hypothesis that PCB-induced changes in the levels of cellular reactive oxygen species (ROS) induce DNA damage resulting in cytotoxicity. Exponentially growing cultures of human nonmalignant breast epithelial cells (MCF10A) were incubated with PCBs for 3 days and assayed for cell number, ROS levels, DNA damage, and cytotoxicity. Exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) or 2-(4-chlorophenyl)benzo-1,4-quinone (4-Cl-BQ), a metabolite of 4-chlorobiphenyl (PCB3), significantly decreased cell number and MTS reduction and increased the percentage of cells with sub-G1 DNA content. Results from electron paramagnetic resonance (EPR) spectroscopy showed a 4-fold increase in the steady-state levels of ROS, which was suppressed in cells pretreated with catalase. EPR measurements in cells treated with 4-Cl-BQ detected the presence of a semiquinone radical, suggesting that the increased levels of ROS could be due to the redox cycling of 4-Cl-BQ. A dose-dependent increase in micronuclei frequency was observed in PCB-treated cells, consistent with an increase in histone 2AX phosphorylation. Treatment of cells with catalase blunted the PCB-induced increase in micronuclei frequency and H2AX phosphorylation that was consistent with an increase in cell survival. Our results demonstrate a PCB-induced increase in cellular levels of ROS causing DNA damage, resulting in cell killing.
Venkatasubbaiah A Venkatesha; Sujatha Venkataraman; Ehab H Sarsour; Amanda L Kalen; Garry R Buettner; Larry W Robertson; Hans-Joachim Lehmler; Prabhat C Goswami
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-07-22
Journal Detail:
Title:  Free radical biology & medicine     Volume:  45     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-20     Completed Date:  2008-12-02     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:  1094-102     Citation Subset:  IM    
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MeSH Terms
Breast / drug effects*,  enzymology*,  pathology
Catalase / metabolism*
Cells, Cultured
Electron Spin Resonance Spectroscopy
Epithelial Cells / drug effects*,  enzymology,  pathology
Histones / drug effects,  metabolism
Micronuclei, Chromosome-Defective / drug effects
Polychlorinated Biphenyls / toxicity*
Reactive Oxygen Species / metabolism
Grant Support
CA 111365/CA/NCI NIH HHS; P42 ES 013661/ES/NIEHS NIH HHS; R01 CA111365/CA/NCI NIH HHS; R01 CA111365-01A2/CA/NCI NIH HHS
Reg. No./Substance:
0/H2AFX protein, human; 0/Histones; 0/Reactive Oxygen Species; DFC2HB4I0K/Polychlorinated Biphenyls; EC

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