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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

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

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

Published In Free Radic Biol Med, (2010 Jul 1)

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.

PubMed ID: 20307652 Exiting the NIEHS site

MeSH Terms: Breast Neoplasms/drug therapy*; Breast Neoplasms/pathology; Breast Neoplasms/physiopathology; Cell Line, Tumor; Cell Proliferation/drug effects; Cell Separation; Cyclin D1/metabolism; Epithelial Cells/drug effects*; Epithelial Cells/metabolism; Epithelial Cells/pathology; Flow Cytometry; Humans; Polychlorinated Biphenyls/pharmacology*; Reactive Oxygen Species/metabolism*; Signal Transduction/drug effects*; Superoxide Dismutase/metabolism

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