Mark A Tapper, Jeffrey S Denny, Jose A Serrano, Richard C Kolanczyk, Barbara R Sheedy, Grace M Overend, Michael W Hornung, Patricia K Schmieder
{"title":"Phenone, Hydroxybenzophenone, and Branched Phenone ER Binding and Vitellogenin Agonism in Rainbow Trout <i>In Vitro</i> Models.","authors":"Mark A Tapper, Jeffrey S Denny, Jose A Serrano, Richard C Kolanczyk, Barbara R Sheedy, Grace M Overend, Michael W Hornung, Patricia K Schmieder","doi":"10.1089/aivt.2018.0008","DOIUrl":null,"url":null,"abstract":"<p><p>Phenones and hydroxy benzophenones are widely used as UV radiation filters, and in the manufacturing of insecticides and pharmaceuticals. Understanding the estrogenic potential these chemicals is of interest to the US Environmental Protection Agency and other international environmental organizations. The current study sequentially combined complementary <i>in vitro</i> rainbow trout estrogen receptor (rtER) binding and liver slice vitellogenin (Vtg) mRNA induction assays in the context of a defined ER-mediated adverse outcome pathway (AOP). Cyclic phenones, branched phenones, and hydroxybenzophenones bound to rtER with relative potency ranging from no affinity to high binding affinity of 0.11%, and many induced Vtg gene expression in rt liver slices. In addition, cyclohexylphenylketone which did not bind rtER binding in cytosol was biotransformed within liver tissue to a chemical that induced Vtg expression.</p>","PeriodicalId":37448,"journal":{"name":"Applied In Vitro Toxicology","volume":" ","pages":"62-74"},"PeriodicalIF":0.0000,"publicationDate":"2019-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370886/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Applied In Vitro Toxicology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1089/aivt.2018.0008","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Health Professions","Score":null,"Total":0}
引用次数: 0
Abstract
Phenones and hydroxy benzophenones are widely used as UV radiation filters, and in the manufacturing of insecticides and pharmaceuticals. Understanding the estrogenic potential these chemicals is of interest to the US Environmental Protection Agency and other international environmental organizations. The current study sequentially combined complementary in vitro rainbow trout estrogen receptor (rtER) binding and liver slice vitellogenin (Vtg) mRNA induction assays in the context of a defined ER-mediated adverse outcome pathway (AOP). Cyclic phenones, branched phenones, and hydroxybenzophenones bound to rtER with relative potency ranging from no affinity to high binding affinity of 0.11%, and many induced Vtg gene expression in rt liver slices. In addition, cyclohexylphenylketone which did not bind rtER binding in cytosol was biotransformed within liver tissue to a chemical that induced Vtg expression.
期刊介绍:
Applied In Vitro Toxicology is a peer-reviewed journal providing the latest research on the application of alternative in vitro testing methods for predicting adverse effects in the pharmaceutical, chemical, and personal care industries. This Journal aims to address important issues facing the various chemical industries, including regulatory requirements; the reduction, refinement, and replacement of animal testing; new screening methods; evaluation of new cell and tissue models; and the most appropriate methods for assessing safety and satisfying regulatory demands. The Journal also delivers the latest views and opinions of developers of new models, end users of the models, academic laboratories that are inventing new tools, and regulatory agencies in the United States, Europe, Latin America, Australia and Asia. Applied In Vitro Toxicology is the journal that scientists involved with hazard identification and risk assessment will read to understand how new and existing in vitro methods are applied, and the questions for which these models provide answers. Applied In Vitro Toxicology coverage includes: -Applied in vitro toxicology industry standards -New technologies developed for applied in vitro toxicology -Data acquisition, cleaning, distribution, and best practices -Data protection, privacy, and policy -Business interests from research to product -The changing role of in vitro toxicology -Visualization and design principles of applied in vitro toxicology infrastructures -Physical interfaces and robotics -Opportunities around applied in vitro toxicology