Antiestrogenicity of environmental polycyclic aromatic hydrocarbons in human breast cancer cells.
The total concentration of 14 polycyclic aromatic hydrocarbons (PAHs) was determined to be 3400-fold greater in a sediment sample from an industrial site on the St. Lawrence River (SLR), NY, than in a sediment sample from a non-industrial site on the Kinderhook Creek (KC), NY. PAH fractions from extracts of the two environmental samples and two reconstituted mixtures as well as the 14 individual PAHs were examined for their toxic, estrogenic, and antiestrogenic activities using MCF-7 focus, recombinant human estrogen receptor (ER) binding, whole-cell ER binding, and 17beta-estradiol (E2) metabolism assays. PAH fractions from the KC and SLR were antiestrogenic; they significantly inhibited the formation of foci elicited in MCF-7 breast cancer cells by 1 nM E2. Eight of the 14 individual PAHs, and the reconstituted mixtures were also antiestrogenic. Results from the whole-cell ER binding assay and the radiometric analysis of E2 metabolism indicate that the PAHs detected in the KC and the SLR environmental samples induce antiestrogenic responses in metabolically intact human breast cancer cells through at least two mechanisms: one involving competition for the ER by a PAH metabolite and the other involving depletion of E2 through induction of metabolism.
Arcaro
K F
KF
School of Public Health, State University of New York at Albany, 12222, USA. arcaro@wadsworth.org
O'Keefe
P W
PW
Yang
Y
Y
Clayton
W
W
Gierthy
J F
JF
D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism / Q000633:toxicity; D004965:Estrogen Antagonists / Q000302:isolation & purification / Q000633:toxicity*; D006801:Humans; D007221:Industry; D011084:Polycyclic Aromatic Hydrocarbons / Q000302:isolation & purification / Q000633:toxicity*; D011874:Radiometry; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012989:Soil Pollutants / Q000032:analysis / Q000633:toxicity*; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004965:Estrogen Antagonists; D011084:Polycyclic Aromatic Hydrocarbons; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D012989:Soil Pollutants; D014316:Tritium; D004958:Estradiol