Incorporation of metabolic enzymes to improve predictivity of reporter gene assay results for estrogenic and anti-androgenic activity

Barbara M.A. van Vugt-Lussenburg*, Rosan B. van der Lee, Hai Yen Man, Irene Middelhof, Abraham Brouwer, Harrie Besselink, Bart van der Burg

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Identification and monitoring of so-called endocrine-disrupting compounds has received ample attention; both the OECD and the United States Environmental Protection Agency (US EPA) have designed tiered testing approaches, involving in vitro bioassays to prioritize and partly replace traditional animal experiments. Since the estrogen (ER) and androgen (AR) receptor are frequent targets of endocrine disrupting chemicals, bioassays detecting interaction with these receptors have a high potential to be of use in risk assessment of endocrine active compounds. However, in many bioassays in vivo hepatic metabolism is not accounted for, which hampers extrapolation to the in vivo situation. In the present study, we have developed a metabolic module using rat liver S9 as an add-on to human cell-based reporter gene assays. The method was applied to reporter gene assays for detection of (anti-) estrogens and (anti-) androgens, but can be extended to cell-based reporter gene assays covering a variety of endpoints related to endocrine disruption.

Original languageEnglish
Pages (from-to)40-48
Number of pages9
JournalReproductive Toxicology
Volume75
Early online date21 Nov 2017
DOIs
Publication statusPublished - Jan 2018

Keywords

  • Bioactivation
  • Endocrine disruption
  • Metabolism
  • Reporter gene assay

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