Antiestrogenicity of environmental polycyclic aromatic hydrocarbons in human breast cancer cells

The total concentration of 14 polycyclic aromatic hydrocarbons (PAHs) was d etermined to be 3400-fold greater in a sediment sample from an industrial s ite on the St. Lawrence River (SLR), NY, than in a sediment sample from a n on-industrial site on the Kinderhook Creek (KC), NY. PAH fractions from ext racts of the two environmental samples and two reconstituted mixtures as we ll as the 14 individual PAHs were examined for their toxic, estrogenic, and antiestrogenic activities using MCF-7 focus, recombinant human estrogen re ceptor (ER) binding, whole-cell ER binding, and 17 beta-estradiol (E-2) met abolism assays. PAH fractions from the KC and SLR were antiestrogenic; they significantly inhibited the formation of foci elicited in MCF-7 breast can cer cells by 1 nM E-2. Eight of the 14 individual PAHs, and the reconstitut ed mixtures were also antiestrogenic. Results from the whole-cell ER bindin g assay and the radiometric analysis of E-2 metabolism indicate that the PA Hs detected in the KC and the SLR environmental samples induce antiestrogen ic responses in metabolically intact human breast cancer cells through at l east two mechanisms: one involving competition for the ER by a PAH metaboli te and the other involving depletion of E-2 through induction of metabolism . Published by Elsevier Science Ireland Ltd.