| Induction of 16[alpha]-/2-Hydroxyestrone Metabolite Ratios in MCF-7 Cells by Pesticides, Carcinogens, and Antiestrogens Does Not Predict Mammary Carcinogens Andrew McDougal and Stephen Safe Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843 USA Abstract
The effects of several pesticides, mammary carcinogens, and antiestrogens on 17ß-estradiol (E2) , 16 - and 2-hydroxylase activities, and 16-/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 16-/2-OHE1 ratios at some concentrations. The 16-/2-OHE1 metabolite ratios for 10-5 M kepone, atrazine, p,p´-DDE, o,p´-DDE, o,p´-DDT, and ß-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 16-/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 16-/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 16-/2-OHE1 metabolite ratios for each class of chemicals and the assay did not predict mammary carcinogens. Key words: antiestrogens, estrogen metabolism, mammary carcinogens, 16-/2-OHE1 ratios, pesticides. Environ Health Perspect 106:203-206 (1998) . [Online 10 March 1998] http://ehpnet1.niehs.nih.gov/docs/1998/106p203-206mcdougal/ abstract.html Address correspondence to S. Safe, Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466 USA. This work was supported by the Novartis Corporation and the Texas Agricultural Experiment Station. Received 23 September 1997 ; accepted 26 November 1997.
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