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標題: Protective role of estrogen receptor-alpha on lower chlorinated PCB congener-induced DNA damage and repair in human tumoral breast cells
作者: Lin, C.H.
Huang, C.L.
Chuang, M.C.
Wang, Y.J.
Chen, D.R.
Chen, S.T.
Lin, P.H.
關鍵字: PCBs;PARP-1 activation;Oxidative stress;poly(adp-ribose) polymerase-1 activation;polychlorinated-biphenyls;pcbs;vascular endothelial-cells;cerebellar granule cells;induced;oxidative stress;subchronic exposure;reactive oxygen;cancer cells;induction;liver
Project: Toxicology Letters
期刊/報告no:: Toxicology Letters, Volume 188, Issue 1, Page(s) 11-19.
Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants. Much of the research has focused on the carcinogenic potential of higher chlorinated PCBs, but accumulative evidence has shown that lower chlorinated PCB congeners have initiating and promoting activities. The goal of this study was to examine the potential of lower chlorinated PCBs, including 2,2',5,5'-tetrachlorobiphenyl (PCB52) and 3,3',4,4'-tetrachlorobiphenyl (PCB77), to induce DNA damage and apoptosis in human MDA-MB-231 (MDA) and MCF-7 breast cancer cells. Results confirmed that treatment of cells with PCB52 and PCB77 resulted in oxidative stress and caspase-dependent apoptosis in both MDA and MCF-7 cells. We noticed that at non-cytotoxic concentrations PCB52 and PCB77-induced decreases in intracellular NAD(P)H in MDA cells but not in MCF-7 cells. Further investigation confirmed that decreases in intracellular NAD(P)H in PCB-treated MDA cells are primarily due to reduction in intracellular NAD(+) pool mediated by poly(ADP-ribose)polymerase-1 activation through formation of DNA strand breaks. Antagonism was observed between PCB52 and PCB77 for the effect on induction of DNA strand breaks in MDA cells. Overall, this evidence demonstrates that at non-cytotoxic concentrations, lower chlorinated PCB congeners are capable of inducing oxidative DNA lesions in ER alpha(-)/MDA cells but not in ER alpha(+)/MCF-7 cells and that functional ER alpha plays a protective role in modulating the PCB-induced DNA damage in human breast cancer cells. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
ISSN: 0378-4274
DOI: 10.1016/j.toxlet.2009.02.009
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