ToxSci Advance Access published online on October 12, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfj009
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1 BioDetection Systems B.V., Amsterdam, The Netherlands
* To whom correspondence should be addressed. Identification of nuclear receptor mediated endocrine activities is important in a variety of fields, ranging from pharmacological and clinical screening, to food and feed safety, toxicological monitoring and risk assessment. Traditionally animal studies such as the Hershberger and Allen-Doisy tests are used for the assessment of androgenic and estrogenic potencies, respectively. To allow fast analysis of the activities of new chemicals, food additives and pharmaceutical compounds, high throughput screening strategies have been developed. Here, a panel of mainly steroidal compounds screened in different in vitro assays, was compared with two human U2-OS cell line-based CALUX® (Chemically Activated LUciferase eXpression) reporter gene assays for androgens (AR CALUX) and estrogens (ER
Received August 25, 2005
Accepted September 27, 2005
In Vitro Toxicology
Comparison of In Vitro and In Vivo Screening Models for Androgenic and Estrogenic Activities
2 BioDetection Systems B.V., Amsterdam, The Netherlands; Instutute for Environmental Studies, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
3 Department of Pharmacology, NV Organon, Oss, The Netherlands
Edwin Sonneveld, E-mail: edwin.sonneveld{at}bds.nl
Abstract 
CALUX). Correlations found between the data of these two CALUX reporter gene assays and data obtained with other in vitro screening assays measuring receptor binding or reporter gene activation (CHO cell line-based) were good (correlation coefficients (r2) between 0.54 and 0.76; p<0.0001). Good correlations were also found between the in vitro and in vivo data (correlation coefficient r2=0.46 for the AR CALUX versus Hershberger assay and r2=0.87 for the ER CALUX versus Allen-Doisy assay). The variations in the results obtained with the reporter gene assays (CALUX versus CHO cell-line based) were relatively small, showing the robustness of these types of assays. Using hierarchical clustering bioactivity relationships between compounds but also relationships between various bioassays were determined. The in vitro assays were found to be good predictors of in vivo androgenic or estrogenic activity of a range of compounds allowing prescreen and/or possible reduction of animal studies.
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