Polychlorinated biphenyl induced ROS signaling delays the entry of quiescent human breast epithelial cells into the proliferative cycle

Leena Chaudhuri; Ehab H Sarsour; Amanda L Kalen; Nùkhet Aykin-Burns; Douglas R Spitz; Prabhat C Goswami

doi:10.1016/j.freeradbiomed.2010.03.012

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Polychlorinated biphenyl induced ROS signaling delays the entry of quiescent human breast epithelial cells into the proliferative cycle

Journal article

Peer reviewed

Polychlorinated biphenyl induced ROS signaling delays the entry of quiescent human breast epithelial cells into the proliferative cycle

Leena Chaudhuri, Ehab H Sarsour, Amanda L Kalen, Nùkhet Aykin-Burns, Douglas R Spitz and Prabhat C Goswami

Free radical biology & medicine, Vol.49(1), pp.40-49

07/01/2010

DOI: 10.1016/j.freeradbiomed.2010.03.012

PMCID: PMC2875331

PMID: 20307652

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Abstract

Polychlorinated biphenyls (PCBs) are environmental chemical contaminants that can produce reactive oxygen species (ROS) by autoxidation of dihydroxy-PCBs and redox-cycling. We investigate the hypothesis that PCB induced perturbations in ROS signaling regulate the entry of quiescent cells into the proliferative cycle. Quiescent MCF-10A human breast epithelial cells were incubated with 0-3 micromolar of 2-(4-chlorophenyl)benzo-1,4-quinone (4-Cl-BQ), 2, 2', 4, 4', 5, 5'-hexachlorobiphenyl (PCB 153), and Aroclor 1254 for 4 days. Cells were replated at a lower density and analyzed for cell cycle phase distributions, ROS levels, MnSOD expression, and cyclin D1 protein levels. Quiescent cells incubated with 4-Cl-BQ showed the maximal delay in entering S phase. This delay was associated with a decrease in MnSOD activity, protein and mRNA levels, and an increase in cellular ROS levels. Results from the mRNA turnover assay showed that the 4-Cl-BQ treatment selectively enhanced the degradation of the 4.2kb MnSOD transcript, while the half-life of the 1.5 kb transcript did not change. Accumulation of cyclin D1 protein levels in replated cells was suppressed in cells treated with 4-Cl-BQ. Pretreatment of quiescent cells with polyethylene glycol-conjugated superoxide dismutase and catalase suppressed 4-Cl-BQ induced increase in ROS levels, which was consistent with an increase in cyclin D1 accumulation, and entry into S phase. These results showed 4-Cl-BQ induced perturbations in ROS signaling inhibit the entry of quiescent cells into S phase.

Cyclin D1 - metabolism

Epithelial Cells - metabolism

Reactive Oxygen Species - metabolism

Polychlorinated Biphenyls - pharmacology

Cell Separation

Epithelial Cells - drug effects

Humans

Epithelial Cells - pathology

Breast Neoplasms - drug therapy

Breast Neoplasms - physiopathology

Flow Cytometry

Signal Transduction - drug effects

Breast Neoplasms - pathology

Cell Line, Tumor

Cell Proliferation - drug effects

Superoxide Dismutase - metabolism

Details

Title: Subtitle: Polychlorinated biphenyl induced ROS signaling delays the entry of quiescent human breast epithelial cells into the proliferative cycle
Creators: Leena Chaudhuri - Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa, Iowa City, Iowa 52242-1181, USA
Ehab H Sarsour
Amanda L Kalen
Nùkhet Aykin-Burns
Douglas R Spitz
Prabhat C Goswami
Resource Type: Journal article
Publication Details: Free radical biology & medicine, Vol.49(1), pp.40-49
DOI: 10.1016/j.freeradbiomed.2010.03.012
PMID: 20307652
PMCID: PMC2875331
NLM abbreviation: Free Radic Biol Med
ISSN: 0891-5849
eISSN: 1873-4596
Publisher: United States
Grant note: P42 ES013661-040002 / NIEHS NIH HHS P42 ES 013661 / NIEHS NIH HHS P42 ES013661 / NIEHS NIH HHS R01 CA111365-05 / NCI NIH HHS P30-CA086862 / NCI NIH HHS CA 111365 / NCI NIH HHS R01 CA111365 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 07/01/2010
Academic Unit: Pathology; Radiation Oncology
Record Identifier: 9984047882102771

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