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ToxSci Advance Access published online on November 7, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn229
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© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Screening of Potentially Hormonally Active Chemicals using Bioluminescent Yeast Bioreporters

John Sanseverino*,{dagger}, Melanie L. Eldridge*, Alice C. Layton*,{dagger}, James P. Easter*, Jason Yarbrough{ddagger}, T. Wayne Schultz*,{ddagger} and Gary S. Sayler*,{dagger}

* The Center for Environmental Biotechnology, The University of Tennessee, Knoxville, Tennessee 37996 {dagger} The Department of Microbiology, The University of Tennessee, Knoxville, Tennessee 37996 {ddagger} The Department of Comparative Medicine, The University of Tennessee, Knoxville, Tennessee 37996

(jsansev{at}utk.edu), (eldrid00{at}utk.edu), (layton{at}utk.edu), (jeaster2{at}utk.edu), (jwyarbrough{at}mail.ag.utk.edu), (tschultz{at}utk.edu), (sayler{at}utk.edu)

Received May 13, 2008; revision received October 22, 2008; accepted October 22, 2008


  Abstract

Saccharomyces cerevisiae bioluminescent bioreporter assays were developed previously to assess a chemical's estrogenic or androgenic disrupting potential. S. cerevisiae BLYES, S. cerevisiae BLYAS, S. cerevisiae BLYR, were used to assess their reproducibility and utility in screening 69, 68, and 71 chemicals for estrogenic, androgenic, and toxic effects, respectively. EC50 values were 6.3 ± 2.4 x 10-10 M (n = 18) and 1.1 ± 0.5 x 10-8 M (n = 13) for BLYES and BLYAS, using 17β-estradiol and 5{alpha}-dihydrotestosterone (DHT) over concentration ranges of 2.5 x 10-12 thru 1.0 x 10-6 M, respectively. Based on analysis of replicate standard curves and comparison to background controls, a set of quantitative rules have been formulated to interpret data and determine if a chemical is potentially hormonally active, toxic, both, or neither. The results demonstrated that these assays are applicable for Tier I chemical screening in EPA's Endocrine Disruptor Screening and Testing Program as well as for monitoring endocrine disrupting activity of unknown chemicals in water.

Key Words: Saccharomyces cerevisiae; bioluminescence; estrogens; androgens; biosensing.


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