- Full (HTML) - Full (PDF) - Related EHP Articles - PubMed:Related Articles - PubMed:Citation - Cited in PMC - Purchase This Issue

Wolfgang Körner,¹ Anne Marie Vinggaard,² Béatrice Térouanne,³ Risheng Ma,⁴ Carise Wieloch,⁵ Margret Schlumpf,⁴ Charles Sultan,³ and Ana M. Soto ⁵

¹Bayerisches Landesamt für Umweltschutz, Augsburg, Germany; ²Danish Veterinary and Food Administration, Institute of Food Safety and Nutrition, Søborg, Denmark; ³INSERM U 439, Pathologie Moléculaire des Récepteurs Nucléaires, Montpellier, France; ⁴University of Zürich, Institute of Pharmacology and Toxicology, Zürich, Switzerland; ⁵Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts, USA

Abstract
We evaluated and compared four in vitro assays to detect androgen agonists and antagonists in an international interlaboratory study. Laboratory 1 used a cell proliferation assay (assay 1) with human mammary carcinoma cells stably transfected with human androgen receptor. The other laboratories used reporter gene assays, two based on stably transfected human prostate carcinoma cells (assay 2) or human mammary carcinoma cells (assay 4) , and the third based on transient transfection of Chinese hamster ovary cells (assay 3) . Four laboratories received four coded compounds and two controls: two steroidal androgens, two antiandrogens, an androgenic control, 5-dihydrotestosterone (DHT) , and an antiandrogenic control, bicalutamide (ICI 176,334) . All laboratories correctly detected the androgenic activity of 4-androsten-3,17-dione and 17-methyltestosterone. For both compounds, the calculated androgenic potencies relative to the positive control (RAPs) remained within one order of magnitude. However, laboratory 3 calculated a 50-fold higher RAP for 4-androsten-3,17-dione. All assays detected and quantified the antiandrogenic effect of vinclozolin [median inhibitory concentration (IC₅₀) values ranging from 1.1 10^-7 M to 4.7 10^-7 M]. In assays 2 and 3, vinclozolin showed partial androgenic activity at the highest concentrations tested. For vinclozolin, calculated antiandrogenic potencies relative to bicalutamide (RAAPs) differed no more than a factor of 10, and IC₅₀ values matched those of bicalutamide. Similarly, we found antiandrogenic activity for tris-(4-chlorophenyl) methanol. RAAP values were between 0.086 and 0.37. Three assays showed cytotoxicity for this compound at or above 1 10^-5 M. In summary, all assays proved sensitive screening tools to detect and quantify androgen receptor-mediated androgenic and antiandrogenic effects of these chemicals accurately, with coefficients of variation between 8 and 90%. Key words: androgenicity, 4-androsten-3, 17-dione, antiandrogenicity, A-SCREEN, bicalutamide, tris-(4-chlorophenyl) methanol (TCPM) , vinclozolin. Environ Health Perspect 112:695-702 (2004) . doi:10.1289/ehp.6715 available via http://dx.doi.org/ [Online 22 January 2004]

Address correspondence to W. Körner, Bayerisches Landesamt für Umweltschutz, Referat Z5, 86177 Augsburg, Germany. Telephone: 49 821 9071 5287. Fax: 49 821 9071 5559. E-mail: wolfgang.koerner@lfu.bayern.de

We thank N. Servant (laboratory 2) and B. Møller Plesning (laboratory 3) for helpful technical assistance.

This work was supported by the Institute de la Santé et de la Recherche Medicale, contract QLK4CT-1999-0142 of the European Community (laboratory 2) ; the National Institutes of Health, grant ES08314C (laboratory 1) ; and the Danish Medical Research Council, grant 9801270 (laboratory 3) .

The authors declare they have no competing financial interests.

Received 29 August 2003 ; accepted 21 January 2004.