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Proteomic profiles of liver microsomes from mice treated with the hepatotumorigenic conazole, triadimefon
Author(s) -
Ortiz Pedro A.,
Chen PeiJen,
Moore Tanya,
Nesnow Stephen,
Winnik Witold M.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1124.10
Subject(s) - triadimefon , microsome , cytochrome p450 , proteome , chemistry , biochemistry , cytochrome , mode of action , metabolism , drug metabolism , xenobiotic , carcinogen , enzyme , biology , fungicide , botany
Triadimefon is a triazole‐based conazole fungicide used in agriculture. This conazole is hepatotoxic and hepatotumorigenic in mice. As part of a large study aimed at determining the mechanism(s) of action of tumorigenic conazoles we have performed a comparative proteome analysis of liver microsomes from mice exposed to triadimefon. Liver microsomes from male CD‐1 mice exposed to tumorigenic doses of triadimefon for 4 days by intraperitoneal injection were prepared. Protein level changes were examined by a 2D difference gel electrophoresis (DIGE) and were identified by nanospray‐liquid chromatography‐tandem mass spectrometry (LC‐MSMS). Seventy‐eight proteins that have shown changes in expression have been identified; the pathways affected by these proteins are the metabolism of xenobiotics by cytochrome P450, proteasome, and the metabolism of glutathione, nitrogen, and glutamate. In addition, we have developed a reverse‐phase protein method to improve mass spectral detection and identification of microsomal cytochrome P450s and UDP‐glucuronosyltransferases proteins, which is being used to monitor changes of hydrophobic proteins that are poorly represented in 2‐D gels. Correlation of the conazole effects on protein expression with toxicology and genomic data will contribute to the elucidation of its mode of action. This is abstract does not necessarily reflect EPA policy.