The Liver S9 Proteome of Rat and Hamster: Global Profiling and Targeted Cytochrome P450 Quantification Reveal...

A comprehensive global proteomic profiling of rat and hamster liver S9 fractions was conducted under basal conditions and following induction with Aroclor 1254 (Aroclor) or phenobarbital/β-naphthoflavone (PBNF). More than 8500 proteins were quantified across conditions. Induction remodeled xenobiotic pathways with conserved increases in CYP1A and CYP2B, larger CYP3A responses in rats under Aroclor, and prominent CYP2F/CYP2G changes in hamsters, alongside a downshift in mitochondrial electron transport and activation of proteostasis networks (heat-shock chaperones). Complementary targeted analysis with stable isotope-labeled standards enabled absolute quantification of 15 cytochrome P450 enzymes, confirming significant inducer-dependent increases across species. This study integrates global proteomic analysis with absolute quantification of CYPs predominantly involved in drug and nitrosamine metabolism for representative enzymes spanning the CYP1A, CYP2A, CYP2C, CYP2D, CYP2E, and CYP3A families in induced and uninduced rat and hamster S9 fractions. The data set and assays serve as a practical reference for DMPK, toxicology, and nitrosamine activation studies and support selection of inducers to tune CYP-mediated oxidative capacity.