INDUCTION OF 16-ALPHA- 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 antiestrog ens on 17 beta-estradiol (E-2), 16 alpha- and 2-hydroxylase activities , and 16 alpha-/2-hydroxyestrone (OHE1) ratios were investigated in MC F-7 cells using a radiometric assay. The mammary carcinogens 7,12-dime thylbenz[a] anthracene (DMBA) and benzo[a]pyrene (BaP), respectively, increased and decreased 16 alpha-/2-OHE1 ratios at some concentrations . The 16 alpha-12-OHE1 metabolite ratios for 10(-5) M kepone, atrazine , p,p'-DDE, o,p'-DDE, o,p'-DDT, and beta-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, an d did not show any specific trend. The effects of a series of direct a nd indirect acting antiestrogens on 16 alpha-/2-OHE1 metabolite ratios were also investigated, and the results were compound specific. Indol e-3-carbinol, tamoxifen, 4'-hydroxytamoxifen and 9-ris-retinoic acid d ecreased the ratio; the effects of all trans-retinoic acid and 2,3,7,8 -tetrachlorodibenzo-p-dioxin were concentration dependent; the antiest rogen ICI 182,780 increased the 16 alpha-/2-OHE1 metabolite ratio. The results indicate that in MCF-7 cells treated with pesticides, mammary carcinogens, and antiestrogens, there were both increased and decreas ed 16 alpha-/2-OHE1 metabolite ratios for each class of chemicals and the assay did not predict mammary carcinogens.