More than just hormones: H295R cells as predictors of reproductive toxicity
| Autor: | Max Kuhn, Jodi M. Maglich, Robert E. Chapin, Mathew T. Pletcher |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
endocrine system
medicine.medical_specialty 3-Hydroxysteroid Dehydrogenases Hydrocortisone Drug Evaluation Preclinical Pharmacology Biology Toxicology Models Biological Cytochrome P-450 Enzyme System In vivo Internal medicine Cell Line Tumor medicine Humans Testosterone Progesterone H295R Models Statistical Cholesterol side-chain cleavage enzyme Colforsin Area under the curve Imidazoles Dehydroepiandrosterone Phosphoproteins In vitro Endocrinology Steroidogenesis CYP17A1 Reproductive toxicology Predictive screening Reproductive toxicity Hormone |
| Zdroj: | Reproductive toxicology (Elmsford, N.Y.). 45 |
| ISSN: | 1873-1708 |
| Popis: | Many of the commonly observed reproductive toxicities associated with therapeutic compounds can be traced to a disruption of the steroidogenic pathway. We sought to develop an in vitro assay that would predict reproductive toxicity and be high throughput in nature. H295R cells, previously validated as having an intact and functional steroidogenic pathway, were treated with 83 known-positive and 79 known-negative proprietary and public-domain compounds. The assay measured the expression of the key enzymes STAR, 3βHSD2, CYP17A1, CYP11B2, CYP19A1, CYP21A2, and CYP11A1 and the hormones DHEA, progesterone, testosterone, and cortisol. We found that a Random Forest model yielded a receiver operating characteristic area under the curve (ROC AUC) of 0.845, with sensitivity of 0.724 and specificity of 0.758 for predicting in vivo reproductive toxicity with this in vitro assay system. |
| Databáze: | OpenAIRE |
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