Screening of Potentially Hormonally Active Chemicals Using Bioluminescent Yeast Bioreporters

Screening of Potentially Hormonally Active Chemicals Using Bioluminescent Yeast Bioreporters
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DOI:
10.1093/toxsci/kfn229
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发表时间:
2009-01-01
影响因子:
3.8
通讯作者:
Sayler, Gary S.
Sayler, Gary S.
中科院分区:
医学2区
文献类型:
--
作者:
Sanseverino, John;Eldridge, Melanie L.;Sayler, Gary S.

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酿酒酵母生物发光生物报告分析是以前开发的,以评估化学品的雌激素或雄激素干扰潜力。S.酿酒酵母BLYES,S.酿酒酵母BLYAS,S.酿酒酵母BLYR,用于评估其重现性和效用,在筛选68,69,和71化学品的雌激素,雄激素和毒性作用分别。使用浓度范围为2.5 x 10(-12)至1.0 x 10(-6)M的17 β-雌二醇和5 α-双氢睾酮,BLYES和BLYAS的EC 50值分别为6.3 +/-2.4 x 10(-10)M(n = 18)和1.1 +/-0.5 x 10(-8)M(n = 13)。基于对重复标准曲线的分析和与背景对照的比较,制定了一套定量规则来解释数据并确定化学品是否具有潜在的生物活性、毒性、两者兼而有之或两者都不具有。结果表明,这些检测方法适用于环境保护局内分泌干扰物筛选和测试计划中的第一层化学品筛选,以及监测水中未知化学品的内分泌干扰活性。
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 68, 69, 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 17 beta-estradiol and 5 alpha-dihydrotestosterone over concentration ranges of 2.5 x 10(-12) through 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 Environmental Protection Agency's Endocrine Disruptor Screening and Testing Program as well as for monitoring endocrine-disrupting activity of unknown chemicals in water.