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Xenobiotica
the fate of foreign compounds in biological systems
Volume 42, 2012 - Issue 6
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General Xenobiochemistry

Effects of the genotoxic compounds, benzo[a]pyrene and cyclophosphamide on phase 1 and 2 activities in EpiDerm™ models

, , , , , , , & show all
Pages 526-537 | Received 25 Oct 2011, Accepted 18 Nov 2011, Published online: 17 Dec 2011
 

Abstract

  1. The micronucleus assay in the 3D human reconstructed EpiDerm™ skin model (RSMN) is a promising new assay for evaluating genotoxicity of dermally applied chemicals.

  2. To complement the testing of metabolically activated chemicals, such as cyclophosphamide (CPA) and benzo[a]pyrene (B[a]P), we measured phase 1 (ethoxyresorufin O-deethylation (EROD) and testosterone metabolism) and 2 activities (UGTs and GSTs) in non-treated and genotoxin treated EpiDerm™ models in a study design which mimics the RSMN assay. The assay involved a three-dose dosing regimen over 72 h to take into account effects e.g. enzyme induction, which requires longer than the standard 2 dose 48-h assay.

  3. These studies demonstrated the presence of basal phase 1 and 2 activities of EpiDerm™ models.

  4. With the exception of GST, all of the activities measured did not reproducibly change over time.

  5. It was possible to measure enzyme induction using this assay design. EROD activity was significantly induced by B[a]P but not by CPA. CPA and B[a]P had little or no reproducible effects on GST and UGT activities.

  6. In conclusion, a number of metabolic enzyme activities were present in the EpiDerm™ skin model and at least the CYP1 family was inducible.

Acknowledgments

The authors thank Dr. Maria Parr, from the Deutsche Sporthochschule, Köln, for generously providing testosterone metabolite standards and Daniel Duche, L’Oreal Recherche; France, for his valued critique of the manuscript.

Declaration of interest

This work was funded by the European Cosmetic Industry Association COLIPA.

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