1. Protective role of estrogen receptor-alpha on lower chlorinated PCB congener-induced DNA damage and repair in human tumoral breast cells.
- Author
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Lin CH, Huang CL, Chuang MC, Wang YJ, Chen DR, Chen ST, and Lin PH
- Subjects
- Apoptosis drug effects, Breast Neoplasms metabolism, Breast Neoplasms pathology, Carcinogens, Environmental chemistry, Caspases metabolism, Cell Line, Tumor, Cell Survival drug effects, Cytoprotection, Dose-Response Relationship, Drug, Enzyme Inhibitors pharmacology, Estrogen Antagonists pharmacology, Estrogen Receptor alpha antagonists & inhibitors, Female, Glutathione metabolism, Humans, Molecular Structure, NADP metabolism, Oxidative Stress drug effects, Poly (ADP-Ribose) Polymerase-1, Poly(ADP-ribose) Polymerase Inhibitors, Poly(ADP-ribose) Polymerases metabolism, Polychlorinated Biphenyls chemistry, Structure-Activity Relationship, Tumor Suppressor Protein p53 metabolism, Breast Neoplasms genetics, Carcinogens, Environmental toxicity, DNA Damage, DNA Repair, Estrogen Receptor alpha metabolism, Gene Expression Regulation, Neoplastic drug effects, Polychlorinated Biphenyls toxicity
- 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 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.
- Published
- 2009
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