Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1909415 | Free Radical Biology and Medicine | 2010 | 10 Pages |
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, 2â², 4, 4â², 5, 5â²-hexachlorobiphenyl (PCB 153), and Aroclor 1254 for 4Â 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 4.2Â kb MnSOD transcript, while the half-life of the 1.5Â 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.
Keywords
PBSPEG-CATPEG-SODFITCMFIPCBCDCFORFMnSODCuZnSODDMSOecSODEDTAEthylenediaminetetraacetic acidBrdUbromodeoxyuridinePolychlorinated biphenylDimethyl sulfoxideextracellular superoxide dismutasemanganese superoxide dismutasecopper zinc superoxide dismutasephosphate buffer salinefluorescein isothiocyanateopen reading framemean fluorescence intensityDHE
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Authors
Leena Chaudhuri, Ehab H. Sarsour, Amanda L. Kalen, Nùkhet Aykin-Burns, Douglas R. Spitz, Prabhat C. Goswami,