Proteomic Analysis of Propiconazole Responses in Mouse Liver‐Comparison of Genomic and Proteomic Profiles

Abstract

We have performed a comprehensive profiling of changes in protein expression of soluble proteins in mouse livers treated with the liver tumorigen, propiconazole, to uncover the pathways altered by this fungicide. Using two‐dimensional gel electrophoresis (2‐DE) and mass spectrometry (MS), we identified 62 proteins altered by propiconazole treatment. These proteins were mapped using Ingenuity Pathway Analyses™ canonical pathways and Tox lists and results compared to genomics results. Seventeen pathways/lists were unique to proteomics, 21 to genomics and 27 were shared by both analyses. The protein network analysis produced interacting sub‐networks including hepatocyte nuclear factor 4α (HNF4α), MYC, and glutathione S‐transferase (GST). Five GST isoforms were identified by proteomic analysis. Hepatic GST activities were compared between mice treated with propiconazole and 2 other conazoles and higher GST activities were found in the tumorigenic conazoles. This study has shown alterations in nuclear receptor activation, metabolism of xenobiotics, biosynthesis of biochemical intermediates, and oxidative stress. It provides insights into toxic mechanisms and/or modes of action of propiconazole required for human health risk assessment. This abstract does not necessarily reflect EPA policy. Mention of trade names of commercial products does not constitute endorsement or recommendation for use.