Induction of 16α-/2-hydroxyestrone metabolite ratios in MCF-7 cells by pesticides, carcinogens, and antiestrogens does not predict mammary carcinogens

The effects of several pesticides, mammary carcinogens, and antiestrogens on 17β-estradiol (E₂), 16α- and 2-hydroxylase activities, and 16α-/2-hydroxyestrone (OHE1) ratios were investigated in MCF-7 cells using a radiometric assay. The mammary carcinogens 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (BaP), respectively, increased and decreased 16α-/2-OHE1 ratios at some concentrations. The 16α-/2-OHE1 metabolite ratios for 10^-5 M kepone, atrazine, p,p'-DDE, o,p'-DDE, o,p'-DDT, and β-hexachlorocyclohexane were 1.82 ± 0.060, 0.71 ± 0.027, 0.66 ± 0.030, 1.56 ± 0.089, 1.14 ± 0.059, and 0.69 ± 0.052 (mean ± standard error), respectively, and did not show any specific trend. The effects of a series of direct and indirect acting antiestrogens on 16α-/2- OHE1 metabolite ratios were also investigated, and the results were compound specific. Indole-3-carbinol, tamoxifen, 4'-hydroxytamoxifen, and 9-cis-retinoic acid decreased the ratio; the effects of all trans-retinoic acid and 2,3,7,8-tetrachlorodibenzo-p-dioxin were concentration dependent; the antiestrogen ICI 182,780 increased the 16α-/2-OHE1 metabolite ratio. The results indicate that in MCF-7 cells treated with pesticides, mammary carcinogens, and antiestrogens, there were both increased and decreased 16α-/2-OHE1 metabolite ratios for each class of chemicals and the assay did not predict mammary carcinogens.