TCDD and PCBs inhibit breast cancer cell proliferation in vitro.
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 17beta-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 approximately = 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 approximately = 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.
Oenga
Gideon N
GN
Wadsworth Center, New York State Department of Health, Albany, NY 12201-0509, USA.
Spink
David C
DC
Carpenter
David O
DO
D001943:Breast Neoplasms / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D004958:Estradiol; D011078:Polychlorinated Biphenyls