Toxaphene is antiestrogenic in a human breast-cancer cell assay

Toxaphene is a complex mixture of chlorinated bornanes, bornenes, and borna dienes and was a heavily used insecticide in the United States until its us e was restricted in 1982. There are conflicting reports regarding the poten tial for toxaphene to induce estrogenic responses in human and nonhuman ani mals. Due to the public concern over environmental estrogens, the estrogeni city of toxaphene was examined in a human breast-cancer cell assay, the MCF -7 focus assay, which is based on in vitro postconfluent cell proliferation and tissue restructuring. In this assay, 0.1-1 nM 17 beta-estradiol (E-2) produces maximum postconfluent proliferation and formation of multicellular nodules or foci. Toxaphene was also tested for its ability (1) to bind the estrogen receptor (ER) in a competitive binding assay using recombinant hu man ER alpha (rhER) and in a whole-cell competitive ER binding assay, and ( 2) to alter the catabolism of E-2 in MCF-7 cell cultures. Results from the MCF-7 focus assay showed: (1) Toxaphene alone was not estrogenic between th e concentrations of 0.5 nM and 10 mu M, (2) toxaphene in binary combination s with chlordane, dieldrin, or endosulfan (alpha or beta) was not estrogeni c, and (3) toxaphene was weakly antiestrogenic (it reduced the number of fo ci induced by 0.1 nM and 0.01 nM E-2). Results from the competitive binding assays showed that (1) toxaphene alone did not bind rhER or ER in MCF-7 ce lls, and (2) toxaphene in binary combinations with other pesticides did not bind rhER. Results from the growth assay and radiometric analysis of E-2 c atabolism showed that (1) toxaphene did not alter the growth rate of MCF-7 cell cultures over 13 d, and (2) toxaphene did not alter the catabolism of E-2. In conclusion, results from the MCF-7 focus assay demonstrate that tox aphene is weakly antiestrogenic rather than estrogenic.