Journal article
Catalase ameliorates polychlorinated biphenyl-induced cytotoxicity in nonmalignant human breast epithelial cells
Free radical biology & medicine, Vol.45(8), pp.1094-1102
2008
DOI: 10.1016/j.freeradbiomed.2008.07.007
PMID: 18691649
Abstract
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-G
1 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.
Details
- Title: Subtitle
- Catalase ameliorates polychlorinated biphenyl-induced cytotoxicity in nonmalignant human breast epithelial cells
- Creators
- Venkatasubbaiah A Venkatesha - Free Radical and Radiation Biology Program, B180 Medical Laboratories, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242-1181, USASujatha Venkataraman - Free Radical and Radiation Biology Program, B180 Medical Laboratories, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242-1181, USAEhab H Sarsour - Free Radical and Radiation Biology Program, B180 Medical Laboratories, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242-1181, USAAmanda L Kalen - Free Radical and Radiation Biology Program, B180 Medical Laboratories, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242-1181, USAGarry R Buettner - Free Radical and Radiation Biology Program, B180 Medical Laboratories, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242-1181, USALarry W Robertson - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA 52242-1181, USAHans-Joachim Lehmler - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA 52242-1181, USAPrabhat C Goswami - Free Radical and Radiation Biology Program, B180 Medical Laboratories, Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242-1181, USA
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.45(8), pp.1094-1102
- DOI
- 10.1016/j.freeradbiomed.2008.07.007
- PMID
- 18691649
- NLM abbreviation
- Free Radic Biol Med
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2008
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Radiation Oncology; Iowa Superfund Research Program
- Record Identifier
- 9984001087402771
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