High-Throughput Screening of Chemical Effects on Steroidogenesis Using H295R Human Adrenocortical Carcinoma Cells

Toxicological Sciences : an Official Journal of the Society of Toxicology
Agnes L KarmausMatthew T Martin

Abstract

Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2060 chemical samples on steroidogenesis via high-performance liquid chromatography followed by tandem mass spectrometry quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a 3 stage screening strategy. The first stage established the maximum tolerated concentration (MTC; ≥ 70% viability) per sample. The second stage quantified changes in hormone levels at the MTC whereas the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were prestimulated with 10 µM forskolin for 48 h to induce steroidogenesis followed by chemical treatment for 48 h. Of the 2060 chemical samples evaluated, 524 samples were selected for 6-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 17β-estradiol and/or testosterone, with 411 chemical samples showing an effec...Continue Reading

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Citations

Oct 30, 2016·Integrated Environmental Assessment and Management·Katherine K CoadyGerald T Ankley
Dec 8, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Derik E HaggardKatie Paul Friedman
May 18, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jon A DoeringGerald T Ankley
Dec 19, 2019·Environmental Health Perspectives·Edo D PellizzariUNKNOWN (Environmental influences on Child Health Outcomes)
Feb 20, 2020·Environmental Health Perspectives·Kamel MansouriRichard S Judson
Sep 15, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Michelle M AngrishBrian N Chorley
Apr 30, 2020·Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association·Max KurlbaumMatthias Kroiss
Sep 30, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Chad DeisenrothRussell S Thomas
Nov 18, 2017·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Caroline Lucia PintoPatience Browne
Jul 22, 2021·Environmental Health Perspectives·Kathryn Z Guyton, Mary K Schubauer-Berigan
Jul 23, 2021·Integrated Environmental Assessment and Management·Natalie BurdenJames R Wheeler
Oct 24, 2018·Environmental Science & Technology·Carlie A LaLoneGerald T Ankley

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