Induction of 16alpha-/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 17beta-estradiol (E2), 16alpha- and 2-hydroxylase activities, and 16alpha-/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 16alpha-/2-OHE1 ratios at some concentrations. The 16alpha-/2-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, and did not show any specific trend. The effects of a series of direct and indirect acting antiestrogens on 16alpha-/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 16alpha-/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 16alpha-/2-OHE1 metabolite ratios for each class of chemicals and the assay did not predict mammary carcinogens.
McDougal
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Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA.
Safe
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D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002273:Carcinogens / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006894:Hydroxyestrones / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D010575:Pesticides / Q000494:pharmacology*; D011237:Predictive Value of Tests; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D004965:Estrogen Antagonists; D006894:Hydroxyestrones; D010575:Pesticides; C026702:16-hydroxyestrone; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase; C024980:2-hydroxyestrone