Protective role of estrogen receptor-alpha on lower chlorinated PCB congener-induced DNA damage and repair in human tumoral breast cells.
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 ERalpha(-)/MDA cells but not in ERalpha(+)/MCF-7 cells and that functional ERalpha plays a protective role in modulating the PCB-induced DNA damage in human breast cancer cells.
Department of Environmental Engineering, National Chung-Hsing University, Taichung 402, Taiwan.
Chia-Hua
CH
Lin
Ching-Lung
CL
Huang
Ming-Chieh
MC
Chuang
Ying-Jan
YJ
Wang
Dar-Ren
DR
Chen
Shou-Tung
ST
Chen
Po-Hsiung
PH
Lin
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002274:Carcinogens, Environmental / Q000737:chemistry / Q000633:toxicity*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D004249:DNA Damage; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D009249:NADP / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000633:toxicity*; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D002274:Carcinogens, Environmental; C506487:ESR1 protein, human; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C009407:2,5,2',5'-tetrachlorobiphenyl; D009249:NADP; D011078:Polychlorinated Biphenyls; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D005978:Glutathione; C028451:3,4,3',4'-tetrachlorobiphenyl