TCDD and PCBs inhibit breast cancer cell proliferation in vitro

• Published in: Toxicology in vitro Vol. 18; no. 6; pp. 811 - 819
• Main Authors: Oenga, Gideon N., Spink, David C., Carpenter, David O.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2004
• Subjects: Ah receptor; Breast cancer cells; Breast Neoplasms - pathology; Cell proliferation; Cell Proliferation - drug effects; Dioxin; Dose-Response Relationship, Drug; Environmental Pollutants - pharmacology; Estradiol - pharmacology; Estrogen; Female; Humans; Polychlorinated biphenyls; Polychlorinated Biphenyls - pharmacology; Polychlorinated Dibenzodioxins - pharmacology; Receptors, Aryl Hydrocarbon - drug effects; Receptors, Aryl Hydrocarbon - physiology; Tumor Cells, Cultured; Cell proliferation; ARNT, aryl hydrocarbon receptor nuclear translocator; iDRE, inhibitory dioxin response elements; FBS, fetal bovine serum; Estrogen; E 2, 17β-estradiol; ER, estrogen receptor; DMSO, dimethylsulfoxide; Ah receptor; AhR, aryl hydrocarbon receptor; PCBs, polychlorinated biphenyls; Rb, retinoblastoma protein; DMEM, Dulbecco's modified Eagle's medium; EDTA, ethylene diamine tetraacetic acid; TCDD, 2,3,7,8,-tetrachlorodibenzo- p-dioxin; Dioxin; Polychlorinated biphenyls; BCS, bovine calf serum; Breast cancer cells; ANOVA, one way analysis of variance
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2004.04.004

The effects on cell proliferation of arylhydrocarbon receptor (AhR) agonists in estrogen-responsive T47D and ZR-75-1 cells were investigated. 2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) and the non- ortho-substituted polychlorinated biphenyl (PCB) congeners, PCB 77, PCB 81, PCB 126, and PCB 169 each inhibited 17β-estradiol (E 2)-stimulated cell proliferation in a dose–responsive manner. In the absence of added E 2, TCDD, PCB 77, PCB 81, and PCB 169 had no significant effect on cell proliferation, while PCB 126 at high concentrations caused slight elevations. The order of effective inhibition of E 2-stimulated cell proliferation by the PCB congeners was: PCB 81>PCB 126≃PCB 169>PCB 77. In the comparative literature, mammalian TEFs for these congeners toxic potency are in the order: PCB 126>PCB 169>PCB 81≃PCB 77 [Organohalogen Compd. 34 (1997) 237]. Our results thus show an unexpected different pattern for the inhibitory effects of PCBs congeners on E 2-mediated cell proliferation.