Protective role of estrogen receptor-alpha on lower chlorinated PCB congener-induced DNA damage and repair in human tumoral breast cells |
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Authors: | Chia-Hua Lin Ching-Lung Huang Ming-Chieh Chuang Ying-Jan Wang Dar-Ren Chen Shou-Tung Chen Po-Hsiung Lin |
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Institution: | 1. Department of Environmental Engineering, National Chung-Hsing University, Taichung 402, Taiwan;2. Department of Environmental and Occupational Health, Medical College, National Cheng Kung University, Tainan, Taiwan;3. Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan |
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Abstract: | 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 ERα(−)/MDA cells but not in ERα(+)/MCF-7 cells and that functional ERα plays a protective role in modulating the PCB-induced DNA damage in human breast cancer cells. |
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Keywords: | 3-AB 3-aminobenzamide 4-OHT 4-hydroxyltamoxifen AhR aryl-hydrocarbon receptor BA benzamide CYP1A1 cytochrome P450 1A1 CYP2B cytochrome P450 2B DCFH-DA 2&prime 7&prime -dichlorodihydrofluorescin diacetate DMSO dimethyl sufoxide ERα estrogen receptor α GSH glutathione MDA MDA-MB-231 pADPr poly(ADP-ribose) polymer PARP-1 poly(ADP-ribose) polymerase-1 PCB126 3 3&prime 4 4&prime 5-pentachlorobiphenyl PCB153 2 2&prime 4 4&prime 5 5&prime -hexachlorobiphenyl PCB52 2 2&prime 5 5&prime -tetrachlorobiphenyl PCB77 3 3&prime 4 4&prime -tetrachlorobiphenyl PCBs polychlorinated biphenyls ROS reactive oxygen species SRB sulforhodamine B |
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