1. In house validation of recombinant yeast estrogen and androgen receptor agonist and antagonist screening assays.
- Author
-
Kolle SN, Kamp HG, Huener HA, Knickel J, Verlohner A, Woitkowiak C, Landsiedel R, and van Ravenzwaay B
- Subjects
- Androgen Receptor Antagonists toxicity, Androgens toxicity, Estrogen Antagonists toxicity, Estrogens toxicity, HeLa Cells, Humans, Reproducibility of Results, Saccharomyces cerevisiae metabolism, Endocrine Disruptors toxicity, Saccharomyces cerevisiae drug effects, Toxicity Tests methods
- Abstract
Besides other modes of action, endocrine disruptors may interact with hormone receptors thereby modifying the physiological function of endogenous hormones. In the present study, we report the results obtained with yeast based assays to detect the (anti-)estrogenic potential (YES) and the (anti-)androgenic potential (YAS) of 105 substances. The results show very high reproducibility and good concordance with literature data of in vivo and/or in vitro studies: the overall true positive rate, true negative rate and accuracy of the assays were 78%, 95%, and 87% (estrogen agonism), and 70%, 97%, and 90% (estrogen antagonism), 88%, 96%, and 95% (androgen agonism) and 81%, 88%, and 85% (androgen antagonism). Furthermore, the performance of the YES assay has been compared to the HeLa based transcriptional activation assay using 20 compounds. The overall true positive rate, true negative rate, and accuracy obtained for the 20 compounds were 100%, 88%, and 95% (mammalian cell based HeLa assay) and 92%, 86%, and 90% (yeast based YES assay). Taken together, the YES and YAS are robust systems, easy to handle and satisfying the requirements for screening systems that can be applied in programs including the US Environmental Protection Agency's Endocrine Disruptor Screening Program., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF